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21st Century Cures Act reforms to the Food and Drug Administration’s (FDA) regulation of the medical device and pharmaceutical industries – Medical Device Overview: Major FDA Reform Bill Becomes Law

Posted in 21st Century Cures Act, FDA Regulatory Affairs, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Medical Devices R&D Investment, tagged Breakthrough Devices, Clarifying Medical Software Regulation, Class 1 and Class II Devices, Classification Panels, Cleaning Instructions and Validation Data Requirement, CLIA Waiver Improvements, Humanitarian Device Exemption (HDE), Institutional Review Board Flexibility, Least Burdensome Device Review on December 19, 2016| Leave a Comment »

21st Century Cures Act reforms to the Food and Drug Administration’s (FDA) regulation of the medical device and pharmaceutical industries – Medical Device Overview: Major FDA Reform Bill Becomes Law

Reporter: Aviva Lev-Ari, PhD, RN

HIGHLIGHTS

The 21st Century Cures Act seeks to expedite development of, and provide priority review for, “breakthrough” devices
The act requires FDA to provide training on the meaning and implementation of the least burdensome review standard, and requires an audit of the results
The act expressly excludes certain categories of medical software from FDA regulation

Major provisions of the act related to medical device regulation found in Subtitle F are listed, below.

President Obama recently signed the 996-page 21st Century Cures Act to implement a variety of reforms to the Food and Drug Administration’s (FDA) regulation of the medical device and pharmaceutical industries.

This alert summarizes the major provisions of the act related to medical device regulation found in Subtitle F.

Section 3051 – Breakthrough Devices

Section 3052 – Humanitarian Device Exemption (HDE)

Section 3053 – Recognition of Standards

Section 3054 – Certain Class 1 and Class II Devices

Section 3055 – Classification Panels

Section 3056 – Institutional Review Board Flexibility

Section 3057 – CLIA Waiver Improvements

Section 3058 – Least Burdensome Device Review

Section 3059 – Cleaning Instructions and Validation Data Requirement

Section 3060 – Clarifying Medical Software Regulation

A copy of the act can be found here.

http://docs.house.gov/billsthisweek/20161128/CPRT-114-HPRT-RU00-SAHR34.pdf

For more information, please contact the Barnes & Thornburg LLP attorney with whom you work or one of the following attorneys in the firm’s Food, Drug & Device Group: Lynn Tyler at (317) 231-7392 or lynn.tyler@btlaw.com; Beth Davis at (404) 264-4025 or beth.davis@btlaw.com; or Alicia Raines Barr at (317) 231-7398 or alicia.rainesbarr@btlaw.com.

Visit us online at www.btlaw.com/food-drug-and-device-law-practices.

SOURCE

http://www.btlaw.com/files/Uploads/Documents/2016%20Alerts/Food,%20Drug%20and%20Device/FDA%20Alert%20-%2021st%20Century%20Cures%20Act.pdf

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM393978.pdf

Artificial Pancreas – Medtronic Receives FDA Approval for World’s First Hybrid Closed Loop System for People with Type 1 Diabetes

Posted in Artificial Pancreas for Type1 Diabetes, FDA Regulatory Affairs, ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics, Medical Devices R&D Investment on September 30, 2016| Leave a Comment »

Artificial Pancreas – Medtronic Receives FDA Approval for World’s First Hybrid Closed Loop System for People with Type 1 Diabetes

Reporter: Aviva Lev-Ari, PhD, RN

Press Release

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Medtronic Receives FDA Approval for World’s First Hybrid Closed Loop System for People with Type 1 Diabetes

The MiniMed® 670G System Features the Company’s Most Advanced SmartGuard(TM) Algorithm To-Date

DUBLIN – Sept. 28, 2016 – Medtronic plc (NYSE:MDT), the global leader in medical technology, today announced it has received U.S. Food and Drug Administration (FDA) approval of its MiniMed® 670G system – the first Hybrid Closed Loop insulin delivery system approved anywhere in the world. Featuring the company’s most advanced algorithm – SmartGuard(TM) HCL – the system is the latest innovation in Medtronic’s phased approach toward developing a fully automated, closed loop system. Medtronic is committed to simplifying and improving diabetes management through the advancement of smart algorithms that achieve greater glucose control with reduced patient input. Through SmartGuard HCL, the system builds on Medtronic’s industry leading algorithms to offer therapy customization so patients and providers can choose from increasing levels of automation that best fit their diabetes management needs.

“With SmartGuard HCL, the ability to automate basal insulin dosing 24 hours a day is a much-anticipated advancement in the diabetes community for the profound impact it may have on managing diabetes – particularly for minimizing glucose variability and maximizing time in the target range,” said Richard M. Bergenstal, M.D., principal investigator of the pivotal study and executive director of the Park Nicollet International Diabetes Center in Minneapolis. “The data from the pivotal trial were compelling and I am confident that this therapy will be well-received by both the clinical and patient community.”

“This significant milestone represents an important step forward in the management of type 1 diabetes and will improve the quality of life for those living with this chronic disease,” said Derek Rapp, president and CEO of JDRF, the leading global organization funding type 1 diabetes research. “We are very encouraged by the speed in which this groundbreaking technology was approved by the FDA, and we are proud of the role JDRF played in achieving this exciting breakthrough. Medtronic and JDRF are committed to ensuring appropriate patient access to this therapy.”

The MiniMed 670G system features the Guardian® Sensor, Medtronic’s newest and most advanced glucose sensor with enhanced accuracy and performance, and a longer 7-day life. The Guardian Sensor, the first and only sensor approved by the FDA to control a hybrid closed loop system, incorporates diagnostic technology that continuously monitors sensor health. Driven by the SmartGuard HCL, the system delivers a variable rate of insulin 24 hours a day based on the personalized needs of the patient, maximizing the time glucose levels are within the target range. It is designed to learn what an individual’s insulin needs are and to take action to minimize both high and low glucose levels. As a result, the system requires minimal input – patients only need to enter mealtime carbohydrates, accept bolus correction recommendations, and periodically calibrate the sensor.

“The FDA approval of the world’s first hybrid closed loop system is a culmination of many years of hard work and close collaboration with the clinical and patient communities to generate the body of evidence needed to advance this technology for those living with diabetes,” said Francine Kaufman, M.D., chief medical officer of the Diabetes Group at Medtronic. “We appreciate the unprecedented speed by which the agency approved our PMA submission to help bring this advanced insulin pump therapy so quickly to U.S. patients living with this challenging disease. We are committed to preparing for commercial launch as quickly as possible while ensuring we provide the most successful rollout of this novel therapy.”

The system is approved for the treatment of people with type 1 diabetes fourteen years of age and older with ongoing studies to expand the indication to additional patient populations. Medtronic will begin commercial release of the MiniMed 670G system in the spring of 2017 with system availability increasing over time. This timeline ensures payer coverage, market and manufacturing readiness, as well as appropriate training of employees, clinicians, educators and patients on the new system. As the company moves toward initial commercial release and subsequently to full production, users of the MiniMed 630G system will be eligible for a Priority Access Program to the MiniMed 670G system as their experience with our newest hardware platform will facilitate an optimal transition. Regulatory approval of the MiniMed 670G is expected outside of the U.S. in the summer of 2017. More details can be found athttp://www.medtronicdiabetes.com/products/priority-access.

MiniMed® 670G System
Click the thumbnail above for a larger image.

About the Diabetes Group at Medtronic (www.medtronicdiabetes.com)
Medtronic is working together with the global community to change the way people manage diabetes. The company aims to transform diabetes care by expanding access, integrating care and improving outcomes, so people living with diabetes can enjoy greater freedom and better health.

About Medtronic
Medtronic plc (www.medtronic.com), headquartered in Dublin, Ireland, is among the world’s largest medical technology, services and solutions companies – alleviating pain, restoring health and extending life for millions of people around the world. Medtronic employs more than 88,000 people worldwide, serving physicians, hospitals and patients in approximately 160 countries. The company is focused on collaborating with stakeholders around the world to take healthcare Further, Together.

Any forward-looking statements are subject to risks and uncertainties such as those described in Medtronic’s periodic reports on file with the Securities and Exchange Commission. Actual results may differ materially from anticipated results.

SOURCE

http://newsroom.medtronic.com/phoenix.zhtml?c=251324&p=irol-newsArticle&ID=2206594

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UPDATED Postmarketing Safety or Effectiveness Data Needed: The 2013 paper was funded by the firm Sarepta Therapeutics, sellers of eteplirsen, a surge in its shares seen after the approval. Eteplirsen will cost patients around $300,000 a year.

Posted in Exosomes, FDA, FDA Regulatory Affairs, Genome Biology, Genomics Pharmacy, Innovations in Neurophysiology & Neuropsychology, Pharmaceutical Discovery, Pharmacogenomics on September 22, 2016| Leave a Comment »

UPDATED Postmarketing Safety or Effectiveness Data Needed: The 2013 paper was funded by the firm Sarepta Therapeutics, sellers of eteplirsen, a surge in its shares seen after the approval. Eteplirsen will cost patients around $300,000 a year.

Curator: Aviva Lev-Ari, PhD, RN

UPDATED on 5/15/2023

FDA advisers narrowly vote in favor of Sarepta’s DMD gene therapy

By Max Bayer May 12, 2023 07:09pm

FDA advisers have narrowly voted in favor of Sarepta Therapeutics’ gene therapy for patients with Duchenne muscular dystrophy (DMD), a stunning decision that runs counter to regulators who expressed skepticism heading into the meeting.

Experts from the Cellular, Tissue, and Gene Therapies Advisory Committee narrowly voted 8 to 6 that the benefit-risk profile of SRP-9001 was strong enough to support accelerated approval even as questions about the gene therapy’s efficacy linger. No members of the committee abstained. SRP-9001 was developed to treat ambulatory patients with a DMD gene mutation.

https://www.fiercebiotech.com/biotech/fda-sarepta-advisors-meeting-dmd-gene-therapy-vote-against

Advisers were tasked with considering four discussion topics about SRP-9001 that centered on the available data on the treatment, the benefit-risk profile of administering it and the implications of allowing the company to use an ongoing phase 3 trial as a confirmatory study. There was little alignment between Sarepta and the FDA’s interpretation of the data, forcing advisers to break the tie.

“I think we owe it to the patients to help them intervene,” said committee member and consumer representative Kathleen O’Sullivan-Fortin, who voted in favor. Others expressed confidence in the safety profile of the gene therapy even amid concerns about the efficacy.

FDA shocks Sarepta, ordering AdComm for DMD gene therapy in sudden change of heart

Sarepta argued that a surrogate endpoint quantifying the expression of micro-dystrophin protein in patients’ muscles was an adequate biomarker to predict clinical benefit and grant accelerated approval. The company cited a natural history study as evidence that correcting the expression addresses the root cause of DMD. The FDA has for years been wary of the proposed biomarker, suggesting as far back as 2018 that Sarepta reconsider the endpoint.

Some of the concerns raised by both committee members and the FDA were aimed at Sarepta’s manufacturing of SRP-9001, which changed between the second and third clinical trials. The new process, which uses a lower percentage of full capsid, is what Sarepta is using in its accelerated approval application. The agency cautioned this could reduce efficacy and increase the risk of side effects. It also wasn’t the process used in Sarepta’s most detailed clinical trial, part of Study 102.

That trial was the only randomized, placebo-controlled study of the gene therapy conducted to date. The trial found that there was not a statistically significant change in functional motor ability between treated patients and placebo as assessed by a common functional rating scale for DMD. Sarepta argued that treated patients had a numerically greater score at all time points, but the FDA concluded those figures were within the bounds of uncertainty, “which is also demonstrated by the lack of even a trend toward statistical significance.”

Sarepta pointed to a post hoc analysis to show that the results varied by age, however, with treated patients ages 4 to 5 showing improvement compared to placebo while 6- to 7-year-old patients had worse function scores than placebo. Sarepta used external control groups from natural history studies to prove a larger benefit between treated and untreated patients across the company’s studies to date. But the FDA said Friday that the natural history data are “challenging to interpret.”

https://www.fiercebiotech.com/biotech/fda-sarepta-advisors-meeting-dmd-gene-therapy-vote-against

UPDATED on 8/18/2019

Sarepta Duchenne drug rejected by FDA in surprise setback

Dive Brief:

In an unexpected decision, the Food and Drug Administration rejected Sarepta Therapeutics’ experimental drug for Duchenne muscular dystrophy, issuing on Monday a Complete Response Letter to the rare disease biotech.

According to Sarepta, the agency cited in its refusal infection risk tied to the drug’s delivery as well as preclinical signs of kidney toxicity. Called Vyondys 53, the medicine is designed for roughly 8% of Duchenne patients with a specific genetic mutation.

Shares in Cambridge, Mass.-based Sarepta fell sharply in post-market trading. Approval of the drug was widely anticipated, making the rejection a setback in Sarepta’s ambitions to treat a wider pool of Duchenne patients.

SOURCE

https://www.biopharmadive.com/news/sarepta-surprise-fda-rejection-duchenne-vyondys-53/561200/

On September 19, the FDA okayed eteplirsen to treat Duchenne muscular dystrophy (DMD), a rare genetic disorder that results in muscle degeneration and premature death. Several of its top officials disagreed with the drug’s approval, questioning how beneficial it will be for patients, as Forbes, MedPage Today and others reported.

http://retractionwatch.com/2016/09/21/amid-controversial-sarepta-approval-decision-fda-head-calls-for-key-study-retraction/

Factors at play for FDA Approval of eteplirsen

the help of the families of young boys with Duchenne muscular dystrophy, emotional scenes from these families who have campaigned for so long
an executive team from Sarepta who wouldn’t give up,

Ed Kaye, Sarepta, CEO – EK: It’s all about resilience. One of the things we’ve had is a group of people of like minds and anytime one of us gets down, somebody else is there to pick you up. One of the things we’ve always done is: Every time we’ve felt sorry for ourselves, we just need to think about those patients and what they go through. Our struggles in comparison very quickly become meaningless. You end up saying to yourself: What am I complaining about? Quit whining; get up and do your job.

and

3. an emerging new philosophy from some within the FDA, eteplirsen, now Exondys 51, was approved in patients with a confirmed mutation of the dystrophin gene amenable to exon 51 skipping.

http://www.fiercebiotech.com/biotech/sarepta-ceo-ed-kaye-fda-courage-nice-and-resilience?utm_medium=nl&utm_source=internal&mrkid=993697&mkt_tok=eyJpIjoiTXpBeU56aGpNREV3T1RZMiIsInQiOiJIM2poTkVOQ0N6YmxaenVHZDM1RlVvbTFmRkdwZGdxQ0pmYXNVOG5PKzRyenFXTkRMV0dcL3l0bVBPNkJ2NFV3Rnc3bWVFVnUwMCs3YVhWeVhvRkkrUU5FMFJ1RndSQTlHWFRnQmFTbUo3ODg9In0%3D

9/19/2016

FDA grants accelerated approval to first drug for Duchenne muscular dystrophy

The accelerated approval of Exondys 51 is based on the surrogate endpoint of dystrophin increase in skeletal muscle observed in some Exondys 51-treated patients. The FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in some patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping. A clinical benefit of Exondys 51, including improved motor function, has not been established. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease for these children and the lack of available therapy.

The FDA granted Exondys 51 fast track designation, which is a designation to facilitate the development and expedite the review of drugs that are intended to treat serious conditions and that demonstrate the potential to address an unmet medical need. It was also granted priority review and orphan drug designation. Priority review status is granted to applications for drugs that, if approved, would be a significant improvement in safety or effectiveness in the treatment of a serious condition. Orphan drug designation provides incentives such as clinical trial tax credits, user fee waiver and eligibility for orphan drug exclusivity to assist and encourage the development of drugs for rare diseases.

SOURCE

http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm

The viability of this drug approval depends on “to be gathered” Postmarketing safety or effectiveness data, aka follow-up confirmatory trials.

Sarepta CEO Ed Kaye on FDA courage, NICE and resilience

BA: When it comes to flexibility, however, the FDA will likely not be flexible if your drug doesn’t prove the desired efficacy in your longer term postmarketing studies. If at the end of this period your drug doesn’t come through, how easy will it be for you to take this off the market? I don’t think anyone, including the FDA, wants a repeat of what happened in 2011 when Roche saw its breast cancer license for Avastin, which had been approved under an accelerated review, pulled after not being safe or effective enough in the follow-up confirmatory trials. But you face this as a possible scenario.

EK: That’s true, but one of the things we’re trying to do to mitigate that is to obviously, with our ongoing studies, prove the efficacy that the FDA wants to see. And you know, if there is a problem with one study then we’d hope to have other data that are supportive. The other thing we’re doing of course is developing that next-generation chemistry in DMD that could prove more effective, so we could certainly consider using that next-gen chemistry to take our work forward and try and make it better.

We have a lot of shots on goal to make sure we can continue to supply a product for these boys, but there is always a risk. If we can’t show efficacy in the way the FDA wants, then yes they have the option to take it off the market.

Need for follow-up confirmatory trials remains outstanding

FDA’s Postmarketing Surveillance Programs

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/ucm090385.htm

FDA’s Regulations and Policies and Procedures for Postmarketing Surveillance Programs

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/ucm090394.htm

Positions on Sarepta’s eteplirsen Scientific Approach

Gene Editing for Exon 51: Why CRISPR Snipping might be better than Exon Skipping for DMD

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2016/01/23/gene-editing-for-exon-51-why-crispr-snipping-might-be-better-than-exon-skipping-for-dmd/

QUOTE START

Retraction Watch

Tracking retractions as a window into the scientific process

Amid controversial Sarepta approval decision, FDA head calls for key study retraction

with one comment

The head of the U.S. Food and Drug Administration (FDA) has called for the retraction of a study about a drug that the agency itself approved earlier this week, despite senior staff opposing the approval.

In a lengthy report Commissioner Robert Califf sent to senior FDA officials on September 16 — that was made public on September 19 — he called for the retraction of a 2013 study published in Annals of Neurologyfunded by the seller of eteplirsen, which showed beneficial effects of the drug in DMD patients. Califf writes inthe report:

The publication, now known to be misleading, should probably be retracted by its authors.

In a footnote in the report, Califf adds:

In view of the scientific deficiencies identified in this analysis, I believe it would be appropriate to initiate a dialogue that would lead to a formal correction or retraction (as appropriate) of the published report.

The study was not the key factor in the agency’s decision to approve the drug, according to Steve Usdin, Washington editor of the publication BioCentury; still, Usdin told Retraction Watch he is “really surprised” at the call for retraction from top FDA staff, the first he has come across in the last two decades.

The 2013 paper was funded by the firm Sarepta Therapeutics, sellers of eteplirsen, which has seen a surge in its shares after the approval. Eteplirsen will cost patients around $300,000 a year.

DMD affects around 1 in 3,600 boys due to a mutation in the gene that codes for the protein dystrophin, which is important for structural stability of muscles. Eteplirsen is the first drug to treat DMD, and was initially given a green light by Janet Woodcock, director of Center for Drug Evaluation and Research, after a split vote from the FDA’s advisory committee. Despite Califf’s issues with the literature supporting the drug’s use in DMD, he did not overturn Woodcock’s decision, and the agency approved the drug this week.

In 2014, an inspection team visited the Nationwide Children’s Hospital in Columbus, Ohio, where the research was conducted, according to the report. In the report, Ellis Unger, director of the Office of Drug Evaluation I in FDA’s Center for Drug Evaluation, notes:

We found the analytical procedures to be typical of an academic research center, seemingly appropriate for what was simply an exploratory phase 1/2 study, but not suitable for an adequate and well controlled study aimed to serve as the basis for a regulatory action. The procedures and controls that one would expect to see in support of a phase 3 registrational trial were not in evidence.

Specifically, Unger describes concerns about blinding during the experiments, and notes:

The immunohistochemistry images were only faintly stained, and had been read by a single technician using an older liquid crystal display (LCD) computer monitor in a windowed room where lighting was not controlled. (The technician had to suspend reading around mid-day, when brighter light began to fill the room and reading became impossible.)

Unger adds:

Having uncovered numerous technical and operational shortcomings in Columbus, our team worked collaboratively with the applicant to develop improved methods for a reassessment of the stored images…This re-analysis, along with the study published in 2013, provides an instructive example of an investigation with extraordinary results that could not be verified.

Luciana Borio, acting chief scientist at the FDA, is cited in the report saying:

I would be remiss if I did not note that the sponsor has exhibited serious irresponsibility by playing a role in publishing and promoting selective data during the development of this product. Not only was there a misleading published article with respect to the results of Study–which has never been retracted—but Sarepta also issued a press release relying on the misleading article and its findings…As determined by the review team, and as acknowledged by Dr. Woodcock, the article’s scientific findings—with respect to the demonstrated effect of eteplirsen on both surrogate and clinical endpoints—do not withstand proper and objective analyses of the data. Sarepta’s misleading communications led to unrealistic expectations and hope for DMD patients and their families.

Here’s how Sarepta describes the study’s findings in the press release Borio refers to:

Published study results showed that once-weekly treatment with eteplirsen resulted in a statistically significant increase from baseline in novel dystrophin, the protein that is lacking in patients with DMD. In addition, eteplirsen-treated patients evaluable on the 6-minute walk test (6MWT) demonstrated stabilization in walking ability compared to a placebo/delayed-treatment cohort. Eteplirsen was well tolerated in the study with no clinically significant treatment-related adverse events. These data will form the basis of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for eteplirsen planned for the first half of 2014.

However, Usdin noted that the drug’s approval and the study are two independent events, adding that the 2013 study just “got the ball rolling” for eteplirsen, and the FDA conducted many of its own ~~experiments~~ analyses, as detailed in the newly released report.

Jerry Mendell, the corresponding author of the study (which has so far been cited 118 times, according to Thomson Reuters Web of Science) from Ohio State University in Columbus, told us the allegations were “unfounded” and said the data are “valid.” Therefore, he added, he will not be approaching the journal for a retraction, noting that the FDA asked him hundreds of questions about the paper and audited the trials.

Clifford Saper, the editor-in-chief of Annals of Neurology from the Beth Israel Deaconess Medical Center (which is part of Harvard Medical School), said in an email:

It takes more than a call by a politician for retraction of a paper. It takes actual evidence.

He added:

If the FDA commissioner has, or knows of someone who has, evidence for an error in a paper published in Annals of Neurology, I encourage him to send that evidence to me and a copy to the authors of the article, for their reply. At that point we will engage in a scientific review of the evidence and make appropriate responses.

Linda Lowes, sixth author of the present study, is the last author of a 2016 study in Physical Therapy that was retracted months after publication. Its notice reads:

This article has been retracted by the author due to unintentional deviations in the use of the described modified technique to assess plagiocephaly in the study participants, such that the use of the modified technique cannot be defended for the stated purpose in this population at this time.

Califf was a cardiologist at Duke University during the high-profile scandal of researcher Anil Potti at Duke, which led to more than 10 retractions, settled lawsuits, and medical board reprimands. In 2015, he told TheTriangle Business Journal:

I wish I had gotten myself more involved earlier…There were systems that were not adequate, as we stated. … That was a tough one, I think, for the whole institution.

We’ve contacted the FDA for comment, and will update the post with anything else we learn.

END QUOTE

Correction 9/21/16 10:44 p.m. eastern: When originally published, this post incorrectly reported that Califf was part of an inspection team that visited the Nationwide Children’s Hospital in Ohio, and attributed quotes from Ellis Unger to Califf. We have made appropriate corrections, and apologize for the error.

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SOURCE

http://retractionwatch.com/2016/09/21/amid-controversial-sarepta-approval-decision-fda-head-calls-for-key-study-retraction/

Related Resources on FDA’s Policies on Drugs:

Read Full Post »

“I’m expecting a flood of trials to get registered,” FDA Commissioner Robert Califf

Posted in FDA Regulatory Affairs, Regulated Clinical Trials: Design, Methods, Components and IRB related issues on September 17, 2016| Leave a Comment »

“I’m expecting a flood of trials to get registered,” FDA Commissioner Robert Califf

Reporter: Aviva Lev-Ari, PhD, RN

By CHARLES PILLER @cpiller

SEPTEMBER 16, 2016

STAT reviewed the data last year, just about 9,000 trials, among nearly 200,000, were subject to the reporting requirements. Under the final rules, the percentage of trials that must report results gradually should rise.

https://www.statnews.com/2016/09/16/clinical-trials-reporting-rules/

WASHINGTON — Researchers will have to publicly report the results of many more clinical trials, including some for drugs and devices that never reach the market, under new government rules announced Friday.

The federal rules, which also require more complete reporting of deaths, clarify and strengthen a 2007 law that requires researchers to report results of many human studies of experimental treatments for ailments such as diabetes, cancer, and heart disease.

Government officials said the new rules are meant to improve compliance with requirements for public registration of trials and posting of data on the ClinicalTrials.gov website. But advocates for transparency in clinical research cautioned that the success of the new rules, which take effect Jan. 18, 2017, will depend on the vigor of government enforcement.

A recent analysis in the journal BMJ found that GlaxoSmithKline, Paxil’s manufacturer, failed to disclose 2001 data showing the drug to be no more effective than a placebo, and was linked to increased suicide attempts by teens.

SEE SOURCE

https://s3.amazonaws.com/public-inspection.federalregister.gov/2016-22129.pdf

New federal rules target woeful public reporting of clinical trial results

Biden threatens funding cuts for researchers who fail to report clinical trial results

“Under the law, it says you must report. If you don’t report, the law says you shouldn’t get funding,” Biden said, citing a STAT investigation that found widespread reporting lapses.

SOURCE

Biden threatens funding cuts for researchers who fail to report clinical trial results

Read Full Post »

Immuno-Therapy Strategies on BioMarker’s cutoff value for defining PD-L1 positive/negative patients: First-line and Second-line setting – FDA stand on BMS’s “Test-free Prescribing” in Opdivo (nivolumab) vs Merck’s “Companion Diagnostic” in Keytruda (pembrolizumab) vs Genetech’s “Complementary Diagnostics” and”Companion Diagnostic”?? in Tecentriq (atezolizumab)

Posted in Biomarkers & Medical Diagnostics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Screening, FDA Regulatory Affairs, Genetics & Innovations in Treatment, Genome Biology, Genomic Testing: Methodology for Diagnosis, Immunotherapy, tagged "Test-free Prescribing", First-line and Second-line setting, Keytruda (pembrolizumab), Opdivo (nivolumab), PD-L1 positive/negative patients, Tecentriq (atezolizumab) on September 13, 2016| Leave a Comment »

Immuno-Therapy Strategies on BioMarker’s cutoff value for defining PD-L1 positive/negative patients: First-line and Second-line setting – FDA stand on BMS’s “Test-free Prescribing” in Opdivo (nivolumab) vs Merck’s “Companion Diagnostic” in Keytruda (pembrolizumab) vs Genetech’s “Complementary Diagnostics” and “Companion Diagnostic”?? in Tecentriq (atezolizumab)

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 3/11/2019

Roche’s I-O drug Tecentriq picks up key first-in-class breast cancer nod

In a first for the immuno-oncology field, Roche’s Tecentriq has a big new approval in breast cancer. And once again, the Swiss drugmaker has nabbed a piece of the immuno-oncology market all for itself.

On Monday, the FDA greenlighted the immuno-oncology drug, in combination with Celgene chemo drug Abraxane, as a treatment for patients with triple-negative breast cancer (TNBC) whose tumors express the protein PD-L1. The go-ahead makes it the first immunotherapy regimen cleared in TNBC—and in breast cancer in general.

Regulators based their positive decision on data presented last fall that showed that adding Tecentriq to Abraxane in newly diagnosed patients could pare down the risk of disease worsening or death by 20%. The duo staved off progression by a median 7.2 months, compared with 5.5 months for Abraxane on its own.

Now, Roche will lead the way in TNBC without market competition from its PD-1/PD-L1 nemeses—at least for now. Tecentriq’s other two therapy areas, bladder cancer and lung cancer, are ultracrowded, thanks to drugs such as Merck’s Keytruda and Bristol-Myers Squibb’s Opdivo, both of which hit the scene before Tecentriq did.

“The response from the physician community has been phenomenal,” Amreen Husain, M.D., global development team leader for Roche immuno-oncology, said in an October interview.

But when it comes to breast cancer, Roche is used to leading the way, and the company will no doubt lean on its marketing expertise—gleaned through years selling drugs like Herceptin and, more recently, Perjeta and Kadcyla—to get Tecentriq off the ground.

Meanwhile, the approval is an exciting one for doctors and patients who’ve battled the notoriously tough-to-treat disease for years with few good options.

https://www.fiercepharma.com/marketing/roche-s-tecentriq-picks-up-key-first-class-breast-cancer-nod-tnbc-ok?mkt_tok=eyJpIjoiWXpFNU5qaGxNV1V3TkRBMSIsInQiOiJVMDdzbWpGQkJuRmpiT2FzaHR3dlwvM2hFQWd5RGkyXC9XMUJ5NHA5YjU5T21jT050Rk9IamtpalNWV3R3YjgzT2lMMEE3OUdpQnhDS3Y2aUNJVW1lMGtpUUY2Z0VGVFJVSkVHUTUrTWVYVjA3VXptMm9WWnlsdVc1VTRRSHg3SXFHIn0%3D

UPDATED on 2/14/2019

Dive Insight:

Checkpoint inhibitors like Merck’s Keytruda (pembrolizumab) have changed cancer care across a number of tumor types, but none are currently approved for prostate cancer. Neither are any of three PARP inhibitors currently on the U.S. market for ovarian and breast cancers.

Merck hopes to change that through these late-stage studies, pairing Keytruda with the PARP inhibitor Lynparza (olaparib), chemotherapy and approved prostate cancer agent Xtandi (enzalutamide).

Patients with mCRPC pose a particular challenge to treat. Metastatic cancer has spread to other parts of the body, while castration-resistant tumors have continued to grow despite surgery or treatment to lower the amount of male sex hormones, or androgens, that typically drive prostate cancer.

Current treatment options for this type of prostate cancer are led by Zytiga (abiraterone acetate), a Johnson & Johnson drug now facing generic competition, and Pfizer and Astellas’ Xtandi.

Merck’s Phase 1b/2 study tested four Keytruda combinations, pairing the immunotherapy with both of those current treatment options as well as with chemotherapy and with Lynparza, which is jointly owned by AstraZeneca and Merck.

Results presented Thursday came from a small number of patients, but showed some positive responses in previously treated patients.

SOURCE

https://www.biopharmadive.com/news/merck-plans-trio-of-phase-3-keytruda-studies-in-prostate-cancer/548466/

UPDATED on 5/1/2018

Dive Insight:

While both Keytruda and Opdivo won initial U.S. approval just months apart in 2014, Bristol-Myers’ drug saw much faster sales growth to start. Securing OKs in first-line lung cancer has been Merck’s ticket to catching Bristol-Myers, and Keytruda sales in the first quarter were roughly even with Opdivo’s.

Merck expects the success of its KEYNOTE-189 study will further drive uptake of Keytruda as a first-line treatment for advanced NSCLC. Results, presented last month at the annual meeting of the American Association of Cancer Research, showed a combination of Keytruda and chemotherapy cut the risk of death in half compared to chemotherapy alone.

Importantly, data supported the combination’s benefit across varying levels of PD-L1 expression , a biomarker used to identify patients most likely to respond to immunotherapy. Merck previously won a conditional approval for the combo from a smaller study, but physicians have been hesitant to broadly prescribe without further data.

Now, impressive results in hand, Merck hopes more doctors will prescribe Keytruda plus chemotherapy to NSCLC patients with PD-L1 expression levels below 50% or even below 1% — patient populations currently not served by Keytruda monotherapy.

SOURCE

https://www.biopharmadive.com/news/merck-keytruda-immunotherapy-lead-q1-earnings-pipeline/522513/

UPDATED on 3/26/2018

Gaining steam in PD-1/L1 race, Roche reports positive PhIII OS data on Tecentriq combo in NSCLC

by brittany meiling — on March 26, 2018 06:29 AM EDT

https://endpts.com/gaining-steam-in-pd-1-l1-race-roche-reports-positive-phiii-os-data-on-tecentriq-combo-in-nsclc/?utm_medium=email&utm_campaign=Monday%20March%2026%202018&utm_content=Monday%20March%2026%202018+CID_12d9cbde6620f32af9d31d31236c94c4&utm_source=ENDPOINTS%20emails&utm_term=Gaining%20steam%20in%20PD-1L1%20race%20Roche%20reports%20positive%20PhIII%20OS%20data%20on%20Tecentriq%20combo%20in%20NSCLC

UPDATED on 3/20/2018

In a phase 3 study, Roche’s Tecentriq combined with chemo beat out solo chemo at cutting the risk of disease worsening or death in previously untreated patients with the squamous form of the disease. As of now, researchers haven’t seen evidence of a benefit to overall survival, but the trial, dubbed IMpower131, is continuing to collect that data.

The results hand Roche the chance to nab a first-to-market lead in the front-line squamous setting. Squamous NSCLC affects just 25% to 30% of all NSCLC patients, but it’s more complicated, and patients have fewer treatment options than those with non-squamous NSCLC, Jefferies analyst Ian Hilliker wrote in a note to clients. Hilliker predicts $1.1 billion in peak sales for Tecentriq in that set of patients.

SOURCE

https://www.fiercepharma.com/pharma/roche-s-tecentriq-triumphs-squamous-lung-cancer-can-it-make-its-mark-against-merck?mkt_tok=eyJpIjoiTlRrM09UQTFNVFEzTjJRNCIsInQiOiJNUnhJMThFZGw5ZERKS1N3Q3dQbGg2dmE1NHhTSFhYZjcycVdMcTAwaTZ1cWxZV3ZJQStqZXJZb0lJUkowNmdXZVk1dnFCc1hVVUlSZitWZ2pPMlJYc25VUXVXY0JxeDdYbUw2XC9uOHgzYWNFb3lObGhrTXd6T25IRWFoTTZTZXcifQ%3D%3D&mrkid=993697

UPDATED on 11/21/2017

Roche Cancer Drug Rises To Challenge Merck, Bristol-Myers

Matthew Herper , FORBES STAFF

Roche’s study had three arms. All patients received carboplatin and paclitaxel, the cancer drug once sold as Taxol. The control group also received Avastin, one of Roche’s best-selling cancer drugs. Then two groups got Tecentriq, one with Avastin and one without. What Roche has announced today is that the Avastin-Tecentriq-chemotherapy combination did better than Avastin and chemotherapy alone, and that the survival results so far are “encouraging.” That leaves a big question: how are the patients who got Tecentriq, but not Avastin, doing?

SOURCE

https://www.forbes.com/sites/matthewherper/2017/11/20/roche-cancer-drug-rises-to-challenge-merck-bristol-myers/#1a08271b52a8

UPDATED on 7/25/2017

Close to a year after Merck $MRK won an accelerated FDA OK to use its PD-1 checkpoint star Keytruda for treating second-line cases head and neck squamous cell carcinoma in combination with platinum-containing chemo, the pharma giant announced that its big Phase III study for that indication failed.

The pivotal KEYNOTE-040 trial failed to meet the primary endpoint on overall survival in comparing the blockbuster checkpoint against standard therapies, the pharma giant reported. But the current approval stands nevertheless, Merck said in a statement.

“The company noted that the FDA remains comfortable with the drug’s current accelerated approval in this indication despite the trial results,” observed Leerink’s Seamus Fernandez. “Importantly, Keytruda appears to have another shot on goal for full approval in H&N cancer, as the Keynote-048 study in first-line patients could, if positive, serve as the confirmatory trial.”

SOURCE

https://endpts.com/merck-hit-with-another-late-stage-setback-on-checkpoint-star-keytruda/?utm_medium=email&utm_campaign=Tuesday%20%20July%2025%202017&utm_content=Tuesday%20%20July%2025%202017+CID_15fd9125b2763ceaf79f421345542d44&utm_source=ENDPOINTS%20emails&utm_term=Merck%20hit%20with%20another%20late-stage%20setback%20on%20checkpoint%20star%20Keytruda

UPDATED on 5/11/2017

Merck increases grip on its lead in lung cancer, winning approval for Keytruda/chemo combo as first-line therapy

by john carroll — on May 10, 2017 05:35 PM EDT Updated: 06:00 PM

https://endpts.com/merck-increases-grip-on-its-lead-in-lung-cancer-winning-approval-for-keytrudachemo-combo-as-first-line-therapy/?utm_medium=email&utm_campaign=Thursday%20%20May%2011%202017&utm_content=Thursday%20%20May%2011%202017+CID_33f2ef8a9bb6f964b9d7568cf79c80be&utm_source=ENDPOINTS%20emails&utm_term=Merck%20increases%20grip%20on%20its%20lead%20in%20lung%20cancer%20winning%20approval%20for%20Keytrudachemo%20combo%20as%20first-line%20therapy

UPDATED on 5/10/2017

Roche’s shocking Tecentriq fail raises red flag for bladder cancer rivals

Roche’s Tecentriq wasn’t supposed to fail its phase 3 trial in second-line bladder cancer. But that’s what it just did—and the data shortfall not only endangers the drug’s conditional FDA approval, but could augur trouble ahead for other checkpoint inhibitors that followed Tecentriq into the field.

Tecentriq, approved last year on the basis of phase 2 data showing a durable response to the drug, failed to prove it could actually prolong patients’ lives, the company said Wednesday. The bladder cancer indication, Tecentriq’s first, accounts for about 70% of the med’s current sales, analysts say, and the FDA could well decide to strike that approval off the drug’s label.

“[W]e assume that this will put this indication at risk of being removed from the label,” Leerink analyst Seamus Fernandez wrote Wednesday morning, noting that the results were unexpected. “This comes as a surprise to us, considering Merck’s Keytruda showed an overall survival benefit.”

SOURCE

http://www.fiercepharma.com/pharma/roche-s-shocking-tecentriq-fail-raises-red-flag-for-bladder-cancer-rivals?utm_medium=nl&utm_source=internal&mrkid=993697&mkt_tok=eyJpIjoiTVRCbFltUXpZMk0wTURRMCIsInQiOiIydnRsZ0xzT3prd3EzYVNoV0xyT1ZCWnFCaDFScVdwd1dyMmpMZjQycU9zOEVJSTVZalY5dHNyQ1E0XC96eXhadkpRSE5JRGoydHNzNFA2WUVaRzRVbUxmNmhicVZ4YkE3c1NmNkhoSUxBK0VmU2dUM3FBWEhrOFp2UHoySXhrUUEifQ%3D%3D

UPDATED on 4/13/2017

World’s Top Ten Cancer Drugs by 2020 (million USD)

https://pharmaceuticalintelligence.com/2017/04/13/worlds-top-ten-cancer-drugs-by-2020-million-usd/

Opdivo Setback May Yield Lessons for Pharma Advancing Immunotherapies With PD-L1 Testing

https://www.genomeweb.com/molecular-diagnostics/opdivo-setback-may-yield-lessons-pharma-advancing-immunotherapies-pd-l1

UPDATED on 10/9/2016

Opdivo (nivolumab) Shows Durable Response in Longest Follow-up for a PD-1 Inhibitor in Previously Treated Advanced Non-Small Cell Lung Cancer

BMY | 6 hours ago

Opdivo (nivolumab) Shows Durable Response in Longest Follow-up for a PD-1 Inhibitor in Previously Treated Advanced Non-Small Cell Lung Cancer

Updated data from CheckMate -057 and -017 show Opdivo-treated patients had tripled the duration of response compared to those treated with docetaxel, with a minimum follow-up of two years

In CheckMate -057, durable responses and complete responses were observed with Opdivo in both PD-L1 expressors and non-expressors

Patient-reported outcomes from CheckMate -057 show favorable overall health status with Opdivo versus docetaxel in previously treated advanced non-small cell lung cancer patients

Bristol-Myers Squibb Company (NYSE: BMY) announced today updated results from two pivotal Phase 3 studies, CheckMate -057 and CheckMate -017, which showed more than one-third of previously treated metastatic non-small cell lung cancer (NSCLC) patients in both trials experienced ongoing responses with Opdivo, compared to no ongoing responses in the docetaxel arm. The median duration of response (DOR) with Opdivo versus docetaxel in CheckMate -057 was 17.2 months (95% CI: 8.4, NE) and 5.6 months (95% CI: 4.4, 6.9), respectively, and in CheckMate -017 it was 25.2 months (95% CI: 9.8, 30.4) and 8.4 months (95% CI: 8.4, NE), respectively. In CheckMate -057, patients with PD-L1 ≥1% had a median DOR of 17.2 months (95% CI: 8.4, NE) and in patients with PD-L1 <1%, it was 18.3 months (95% CI: 5.5, NE). In both studies, durability of response was observed in both PD-L1 expressors and non-expressors, and in CheckMate -057, one out of the four complete responses occurred in a patient with <1% PD-L1 expression.

There were no new safety signals identified for Opdivo in the pooled safety analysis from both studies. No new treatment-related deaths occurred between one and two years’ minimum follow-up despite the longer treatment exposure, and new events were observed in 11/418 patients with an additional one year of follow up.

These findings were presented today, October 9, during a poster discussion session at the 2016 European Society for Medical Oncology Congress from 3:46-4:06 p.m. CEST (Abstract #1215PD).

“Further evaluation of Opdivo in previously treated non-small cell lung cancer showed continued superior survival and the potential for durable responses compared to docetaxel across histologies in this patient population,” said Martin Reck, M.D., Ph.D., head of thoracic oncology at the Hospital Grosshansdorf. “Notably, the median duration of response with Opdivo was more than three times that observed with docetaxel.”

For a review of all the complexities involved in the emerging market for BioMarkers in Immuno-Therapy, see

Opdivo Setback May Yield Lessons for Pharma Advancing Immunotherapies With PD-L1 Testing

https://www.genomeweb.com/molecular-diagnostics/opdivo-setback-may-yield-lessons-pharma-advancing-immunotherapies-pd-l1

PD-L1 testing as part of the tumor profiling workup for patients. Diaceutics’ surveys show a sharp uptick in the number of labs offering PD-L1 testing over the past year-and-a-half and 52 labs in the US offer at least one PD-L1 test. The company also reviewed biomarkers being studied in 95 Phase II/III NSCLC, and found that approximately half are incorporating patients’ PD-L1 status either alone or in combination with other markers, such as EGFR and ALK mutations.

At Cancer Genetics over the past year, there has also been a notable ramp up in orders for PD-L1 testing for lung cancer patients, but also for melanoma and head and neck cancer patients.

Labs are also challenged by having to decide whether to invest in validating and offering all four FDA-approved PD-L1 tests. “If you look from a laboratory perspective, in the ideal world, you need one test, and clear instructions about the algorithm and cutoff values to assign patients to treatment,” Braendle said. “Four different tests creates quite a confusing situation for the labs and the physicians.”

SOURCES

Diaceutics Group Report Reveals Significant Real-Time PD-L1 Testing Gaps in the US

http://www.diaceutics.com/diaceutics-group-report-reveals-significant-real-time-pd-l1-testing-gaps-in-the-us-3/

Opdivo Setback May Yield Lessons for Pharma Advancing Immunotherapies With PD-L1 Testing

https://www.genomeweb.com/molecular-diagnostics/opdivo-setback-may-yield-lessons-pharma-advancing-immunotherapies-pd-l1

Read Full Post »

Genomics Orientations for Personalized Medicine: Request for Book Review Writing on Amazon.com

Posted in CRISPR/Cas9 & Gene Editing, DNA repair, Epigenetics and Environmental Factors, FDA, FDA Regulatory Affairs, Gene Regulation, Gene Regulation and Evolution, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Genomic Endocrinology, Genomic Testing: Methodology for Diagnosis, Personalized and Precision Medicine & Genomic Research, Pharmaceutical R&D Informatics, Pharmacogenomics, Population genetics, Population Health Management, Population Health Management, Genetics & Pharmaceutical on September 11, 2016| Leave a Comment »

Series B: Frontiers in Genomics Research

Content Consultant: Larry H Bernstein, MD, FCAP

2.1.5.12

2.1.5.12 Genomics Orientations for Personalized Medicine: Request for Book Review Writing on Amazon.com, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 2: CRISPR for Gene Editing and DNA Repair

Genomics Orientations for Personalized Medicine

Volume One

http://www.amazon.com/dp/B018DHBUO6

electronic Table of Contents

Chapter 1

1.1 Advances in the Understanding of the Human Genome The Initiation and Growth of Molecular Biology and Genomics – Part I

1.2 CRACKING THE CODE OF HUMAN LIFE: Milestones along the Way – Part IIA

1.3 DNA – The Next-Generation Storage Media for Digital Information

1.4 CRACKING THE CODE OF HUMAN LIFE: Recent Advances in Genomic Analysis and Disease – Part IIC

1.5 Advances in Separations Technology for the “OMICs” and Clarification of Therapeutic Targets

1.6 Genomic Analysis: FLUIDIGM Technology in the Life Science and Agricultural Biotechnology

Chapter 2

2.1 2013 Genomics: The Era Beyond the Sequencing of the Human Genome: Francis Collins, Craig Venter, Eric Lander, et al.

2.2 DNA structure and Oligonucleotides

2.3 Genome-Wide Detection of Single-Nucleotide and Copy-Number Variation of a Single Human Cell

2.4 Genomics and Evolution

2.5 Protein-folding Simulation: Stanford’s Framework for Testing and Predicting Evolutionary Outcomes in Living Organisms – Work by Marcus Feldman

2.6 The Binding of Oligonucleotides in DNA and 3-D Lattice Structures

2.7 Finding the Genetic Links in Common Disease: Caveats of Whole Genome Sequencing Studies

Chapter 3

3.1 Big Data in Genomic Medicine

3.2 CRACKING THE CODE OF HUMAN LIFE: The Birth of Bioinformatics & Computational Genomics – Part IIB

3.3 Expanding the Genetic Alphabet and linking the Genome to the Metabolome

3.4 Metabolite Identification Combining Genetic and Metabolic Information: Genetic Association Links Unknown Metabolites to Functionally Related Genes

3.5 MIT Scientists on Proteomics: All the Proteins in the Mitochondrial Matrix identified

3.6 Identification of Biomarkers that are Related to the Actin Cytoskeleton

3.7 Genetic basis of Complex Human Diseases: Dan Koboldt’s Advice to Next-Generation Sequencing Neophytes

3.8 MIT Team Researches Regulatory Motifs and Gene Expression of Erythroleukemia (K562) and Liver Carcinoma (HepG2) Cell Lines

Chapter 4

4.1 ENCODE Findings as Consortium

4.2 ENCODE: The Key to Unlocking the Secrets of Complex Genetic Diseases

4.3 Reveals from ENCODE Project will Invite High Synergistic Collaborations to Discover Specific Targets

4.4 Human Variome Project: encyclopedic catalog of sequence variants indexed to the human genome sequence

4.5 Human Genome Project – 10th Anniversary: Interview with Kevin Davies, PhD – The $1000 Genome

4.6 Quantum Biology And Computational Medicine

4.7 The Underappreciated EpiGenome

4.8 Unraveling Retrograde Signaling Pathways

4.9 “The SILENCE of the Lambs” Introducing The Power of Uncoded RNA

4.10 DNA: One man’s trash is another man’s treasure, but there is no JUNK after all

Chapter 5

5.1 Paradigm Shift in Human Genomics – Predictive Biomarkers and Personalized Medicine – Part 1

5.2 Computational Genomics Center: New Unification of Computational Technologies at Stanford

5.3 Personalized Medicine: An Institute Profile – Coriell Institute for Medical Research: Part 3

5.4 Cancer Genomics – Leading the Way by Cancer Genomics Program at UC Santa Cruz

5.5 Genome and Genetics: Resources @Stanford, @MIT, @NIH’s NCBCS

5.6 NGS Market: Trends and Development for Genotype-Phenotype Associations Research

5.7 Speeding Up Genome Analysis: MIT Algorithms for Direct Computation on Compressed Genomic Datasets

5.8 Modeling Targeted Therapy

5.9 Transphosphorylation of E-coli Proteins and Kinase Specificity

5.10 Genomics of Bacterial and Archaeal Viruses

Chapter 6

6.1 Directions for Genomics in Personalized Medicine

6.2 Ubiquinin-Proteosome pathway, Autophagy, the Mitochondrion, Proteolysis and Cell Apoptosis: Part III

6.3 Mitochondrial Damage and Repair under Oxidative Stress

6.4 Mitochondria: More than just the “Powerhouse of the Cell”

6.5 Mechanism of Variegation in Immutans

6.6 Impact of Evolutionary Selection on Functional Regions: The imprint of Evolutionary Selection on ENCODE Regulatory Elements is Manifested between Species and within Human Populations

6.7 Cardiac Ca2+ Signaling: Transcriptional Control

6.8 Unraveling Retrograde Signaling Pathways

6.9 Reprogramming Cell Fate

6.10 How Genes Function

6.11 TALENs and ZFNs

6.12 Zebrafish—Susceptible to Cancer

6.13 RNA Virus Genome as Bacterial Chromosome

6.14 Cloning the Vaccinia Virus Genome as a Bacterial Artificial Chromosome

6.15 Telling NO to Cardiac Risk- DDAH Says NO to ADMA(1); The DDAH/ADMA/NOS Pathway(2)

6.16 Transphosphorylation of E-coli proteins and kinase specificity

6.17 Genomics of Bacterial and Archaeal Viruses

6.18 Diagnosing Diseases & Gene Therapy: Precision Genome Editing and Cost-effective microRNA Profiling

Chapter 7

7.1 Harnessing Personalized Medicine for Cancer Management, Prospects of Prevention and Cure: Opinions of Cancer Scientific Leaders @ http://pharmaceuticalintelligence.com

7.2 Consumer Market for Personal DNA Sequencing: Part 4

7.3 GSK for Personalized Medicine using Cancer Drugs Needs Alacris Systems Biology Model to Determine the In Silico Effect of the Inhibitor in its “Virtual Clinical Trial”

7.4 Drugging the Epigenome

7.5 Nation’s Biobanks: Academic institutions, Research institutes and Hospitals – vary by Collections Size, Types of Specimens and Applications: Regulations are Needed

7.6 Personalized Medicine: Clinical Aspiration of Microarrays

Chapter 8

8.1 Personalized Medicine as Key Area for Future Pharmaceutical Growth

8.2 Inaugural Genomics in Medicine – The Conference Program, 2/11-12/2013, San Francisco, CA

8.3 The Way With Personalized Medicine: Reporters’ Voice at the 8th Annual Personalized Medicine Conference, 11/28-29, 2012, Harvard Medical School, Boston, MA

8.4 Nanotechnology, Personalized Medicine and DNA Sequencing

8.5 Targeted Nucleases

8.6 Transcript Dynamics of Proinflammatory Genes

8.7 Helping Physicians identify Gene-Drug Interactions for Treatment Decisions: New ‘CLIPMERGE’ program – Personalized Medicine @ The Mount Sinai Medical Center

8.8 Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing[1]

8.9 Diagnosing Diseases & Gene Therapy: Precision Genome Editing and Cost-effective microRNA Profiling

Chapter 9

9.1 Personal Tale of JL’s Whole Genome Sequencing

9.2 Inspiration From Dr. Maureen Cronin’s Achievements in Applying Genomic Sequencing to Cancer Diagnostics

9.3 Inform Genomics Developing SNP Test to Predict Side Effects, Help MDs Choose among Chemo Regimens

9.4 SNAP: Predict Effect of Non-synonymous Polymorphisms: How Well Genome Interpretation Tools could Translate to the Clinic

9.5 LEADERS in Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment: Part 2

9.6 The Initiation and Growth of Molecular Biology and Genomics – Part I

9.7 Personalized Medicine-based Cure for Cancer Might Not Be Far Away

9.8 Personalized Medicine: Cancer Cell Biology and Minimally Invasive Surgery (MIS)

Chapter 10

10.1 Pfizer’s Kidney Cancer Drug Sutent Effectively caused REMISSION to Adult Acute Lymphoblastic Leukemia (ALL)

10.2 Imatinib (Gleevec) May Help Treat Aggressive Lymphoma: Chronic Lymphocytic Leukemia (CLL)

10.3 Winning Over Cancer Progression: New Oncology Drugs to Suppress Passengers Mutations vs. Driver Mutations

10.4 Treatment for Metastatic HER2 Breast Cancer

10.5 Personalized Medicine in NSCLC

10.6 Gene Sequencing – to the Bedside

10.7 DNA Sequencing Technology

10.8 Nobel Laureate Jack Szostak Previews his Plenary Keynote for Drug Discovery Chemistry

Chapter 11

11.1 mRNA Interference with Cancer Expression

11.2 Angiogenic Disease Research Utilizing microRNA Technology: UCSD and Regulus Therapeutics

11.3 Sunitinib brings Adult acute lymphoblastic leukemia (ALL) to Remission – RNA Sequencing – FLT3 Receptor Blockade

11.4 A microRNA Prognostic Marker Identified in Acute Leukemia

11.5 MIT Team: Microfluidic-based approach – A Vectorless delivery of Functional siRNAs into Cells.

11.6 Targeted Tumor-Penetrating siRNA Nanocomplexes for Credentialing the Ovarian Cancer Oncogene ID4

11.7 When Clinical Application of miRNAs?

11.8 How mobile elements in “Junk” DNA promote cancer. Part 1: Transposon-mediated tumorigenesis,

11.9 Potential Drug Target: Glycolysis Regulation – Oxidative Stress-responsive microRNA-320

11.10 MicroRNA Molecule May Serve as Biomarker

11.11 What about Circular RNAs?

Chapter 12

12.1 The “Cancer Establishments” Examined by James Watson, Co-discoverer of DNA w/Crick, 4/1953

12.2 Otto Warburg, A Giant of Modern Cellular Biology

12.3 Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?

12.4 Hypothesis – Following on James Watson

12.5 AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo

12.6 AKT signaling variable effects

12.7 Rewriting the Mathematics of Tumor Growth; Teams Use Math Models to Sort Drivers from Passengers

12.8 Phosphatidyl-5-Inositol signaling by Pin1

Chapter 13

13.1 Nanotech Therapy for Breast Cancer

13.2 BRCA1 a tumour suppressor in breast and ovarian cancer – functions in transcription, ubiquitination and DNA repair

13.3 Exome sequencing of serous endometrial tumors shows recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes

13.4 Recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes in serous endometrial tumors

13.5 Prostate Cancer: Androgen-driven “Pathomechanism” in Early onset Forms of the Disease

13.6 In focus: Melanoma Genetics

13.7 Head and Neck Cancer Studies Suggest Alternative Markers More Prognostically Useful than HPV DNA Testing

13.8 Breast Cancer and Mitochondrial Mutations

13.9 Long noncoding RNA network regulates PTEN transcription

Chapter 14

14.1 HBV and HCV-associated Liver Cancer: Important Insights from the Genome

14.2 Nanotechnology and HIV/AIDS treatment

14.3 IRF-1 Deficiency Skews the Differentiation of Dendritic Cells

14.4 Sepsis, Multi-organ Dysfunction Syndrome, and Septic Shock: A Conundrum of Signaling Pathways Cascading Out of Control

14.5 Five Malaria Genomes Sequenced

14.6 Rheumatoid Arthritis Risk

14.7 Approach to Controlling Pathogenic Inflammation in Arthritis

14.8 RNA Virus Genome as Bacterial Chromosome

14.9 Cloning the Vaccinia Virus Genome as a Bacterial Artificial Chromosome

Chapter 15

15.1 Personalized Cardiovascular Genetic Medicine at Partners HealthCare and Harvard Medical School

15.2 Congestive Heart Failure & Personalized Medicine: Two-gene Test predicts response to Beta Blocker Bucindolol

15.3 DDAH Says NO to ADMA(1); The DDAH/ADMA/NOS Pathway(2)

15.4 Peroxisome Proliferator-Activated Receptor (PPAR-gamma) Receptors Activation: PPARγ Transrepression for Angiogenesis in Cardiovascular Disease and PPARγ Transactivation for Treatment of Diabetes

15.5 BARI 2D Trial Outcomes

15.6 Gene Therapy Into Healthy Heart Muscle: Reprogramming Scar Tissue In Damaged Hearts

15.7 Obstructive coronary artery disease diagnosed by RNA levels of 23 genes – CardioDx, a Pioneer in the Field of Cardiovascular Genomic Diagnostics

15.8 Ca2+ signaling: transcriptional control

15.9 Lp(a) Gene Variant Association

15.9.1 Two Mutations, in the PCSK9 Gene: Eliminates a Protein involved in Controlling LDL Cholesterol

15.9.2. Genomics & Genetics of Cardiovascular Disease Diagnoses: A Literature Survey of AHA’s Circulation Cardiovascular Genetics, 3/2010 – 3/2013

15.9.3 Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

15.9.4 The Implications of a Newly Discovered CYP2J2 Gene Polymorphism Associated with Coronary Vascular Disease in the Uygur Chinese Population

15.9.5 Gene, Meis1, Regulates the Heart’s Ability to Regenerate after Injuries.

15.10 Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

15.11 How Might Sleep Apnea Lead to Serious Health Concerns like Cardiac and Cancers?

Chapter 16

16.1 Can Resolvins Suppress Acute Lung Injury?

16.2 Lipoxin A4 Regulates Natural Killer Cell in Asthma

16.3 Biological Therapeutics for Asthma

16.4 Genomics of Bronchial Epithelial Dysplasia

16.5 Progression in Bronchial Dysplasia

Chapter 17

17.1 Breakthrough Digestive Disorders Research: Conditions Affecting the Gastrointestinal Tract.

17.2 Liver Endoplasmic Reticulum Stress and Hepatosteatosis

17.3 Biomarkers-identified-for-recurrence-in-hbv-related-hcc-patients-post-surgery

17.4 Usp9x: Promising Therapeutic Target for Pancreatic Cancer

17.5 Battle of Steve Jobs and Ralph Steinman with Pancreatic cancer: How We Lost

Chapter 18

18.1 Ubiquitin Pathway Involved in Neurodegenerative Disease

18.2 Genomic Promise for Neurodegenerative Diseases, Dementias, Autism Spectrum, Schizophrenia, and Serious Depression

18.3 Neuroprotective Therapies: Pharmacogenomics vs Psychotropic Drugs and Cholinesterase Inhibitors

18.4 Ustekinumab New Drug Therapy for Cognitive Decline Resulting from Neuroinflammatory Cytokine Signaling and Alzheimer’s Disease

18.5 Cell Transplantation in Brain Repair

18.6 Alzheimer’s Disease Conundrum – Are We Near the End of the Puzzle?

Chapter 19

19.1 Genetics and Male Endocrinology

19.2 Genomic Endocrinology and its Future

19.3 Commentary on Dr. Baker’s post “Junk DNA Codes for Valuable miRNAs: Non-coding DNA Controls Diabetes”

19.4 Therapeutic Targets for Diabetes and Related Metabolic Disorders

19.5 Secondary Hypertension caused by Aldosterone-producing Adenomas caused by Somatic Mutations in ATP1A1 and ATP2B3 (adrenal cortical; medullary or Organ of Zuckerkandl is pheochromocytoma)

19.6 Personal Recombination Map from Individual’s Sperm Cell and its Importance

19.7 Gene Trap Mutagenesis in Reproductive Research

19.8 Pregnancy with a Leptin-Receptor Mutation

19.9 Whole-genome Sequencing in Probing the Meiotic Recombination and Aneuploidy of Single Sperm Cells

19.10 Reproductive Genetic Testing

Chapter 20

20.1 Genomics & Ethics: DNA Fragments are Products of Nature or Patentable Genes?

20.2 Understanding the Role of Personalized Medicine

20.3 Attitudes of Patients about Personalized Medicine

20.4 Genome Sequencing of the Healthy

20.5 Genomics in Medicine – Tomorrow’s Promise

20.6 The Promise of Personalized Medicine

20.7 Ethical Concerns in Personalized Medicine: BRCA1/2 Testing in Minors and Communication of Breast Cancer Risk

20.8 Genomic Liberty of Ownership, Genome Medicine and Patenting the Human Genome

Chapter 21

Recent Advances in Gene Editing Technology Adds New Therapeutic Potential for the Genomic Era: Medical Interpretation of the Genomics Frontier – CRISPR – Cas9

Introduction

21.1 Introducing CRISPR/Cas9 Gene Editing Technology – Works by Jennifer A. Doudna

21.1.1 Ribozymes and RNA Machines – Work of Jennifer A. Doudna

21.1.2 Evaluate your Cas9 gene editing vectors: CRISPR/Cas Mediated Genome Engineering – Is your CRISPR gRNA optimized for your cell lines?

21.1.3 2:15 – 2:45, 6/13/2014, Jennifer Doudna “The biology of CRISPRs: from genome defense to genetic engineering”

21.1.4 Prediction of the Winner RNA Technology, the FRONTIER of SCIENCE on RNA Biology, Cancer and Therapeutics & The Start Up Landscape in BostonGene Editing – New Technology The Missing link for Gene Therapy?

21.2 CRISPR in Other Labs

21.2.1 CRISPR @MIT – Genome Surgery

21.2.2 The CRISPR-Cas9 System: A Powerful Tool for Genome Engineering and Regulation

Yongmin Yan and Department of Gastroenterology, Hepatology & Nutrition, University of Texas M.D. Anderson Cancer, Houston, USADaoyan Wei^*

21.2.3 New Frontiers in Gene Editing: Transitioning From the Lab to the Clinic, February 19-20, 2015 | The InterContinental San Francisco | San Francisco, CA

21.2.4 Gene Therapy and the Genetic Study of Disease: @Berkeley and @UCSF – New DNA-editing technology spawns bold UC initiative as Crispr Goes Global

21.2.5 CRISPR & MAGE @ George Church’s Lab @ Harvard

21.3 Patents Awarded and Pending for CRISPR

21.3.1 Litigation on the Way: Broad Institute Gets Patent on Revolutionary Gene-Editing Method

21.3.2 The Patents for CRISPR, the DNA editing technology as the Biggest Biotech Discovery of the Century

2.4 CRISPR/Cas9 Applications

21.4.1 Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells using a bacterial CRISPR/Cas

21.4.2 CRISPR: Applications for Autoimmune Diseases @UCSF

21.4.3 In vivo validated mRNAs

21.4.4 Delineating a Role for CRISPR-Cas9 in Pharmaceutical Targeting

21.4.5 Where is the most promising avenue to success in Pharmaceuticals with CRISPR-Cas9?

21.4.6 Level of Comfort with Making Changes to the DNA of an Organism

21.4.7 Who will be the the First to IPO: Novartis bought in to Intellia (UC, Berkeley) as well as Caribou (UC, Berkeley) vs Editas (MIT)??

21.4.8 CRISPR/Cas9 Finds Its Way As an Important Tool For Drug Discovery & Development

Summary

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Thriving Three Groups on LinkedIn

Posted in 3D Printing for Medical Application, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, BioTechnology - Venture Creation, Venture Capital, CANCER BIOLOGY & Innovations in Cancer Therapy, Cardiac and Cardiovascular Surgical Procedures, Cardiovascular Research, Computational Biology/Systems and Bioinformatics, CRISPR/Cas9 & Gene Editing, DNA repair, Drug Delivery Platform Technology, Epigenetics and Environmental Factors, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Genomic Testing: Methodology for Diagnosis, Global Partnering & Biotech Investment, Health Law & Patient Safety, HealthCare IT, Human Immune System in Health and in Disease, Immuno-Oncology & Genomics, Immunodiagnostics, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, International Global Work in Pharmaceutical, Interventional Oncology: Radiofrequency Ablation, Transarterial Chemoembolization, Microwave Ablation and Irreversible Electroporation (IRE), Interviews with Scientific Leaders, Investment in Technological Breakthrough, Medical Devices R&D and Inventions, Origins of Cardiovascular Disease, Pharmacotherapy of Cardiovascular Disease on July 20, 2016| Leave a Comment »

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Groups Launcher and Group Manager: Aviva Lev-Ari, PhD, RN

CRISPR’s Unwanted off-target effects: Need for safety study designs with Gene-Editing

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, FDA, FDA Regulatory Affairs, Genome Biology, Genomic Expression, tagged adverse events, CRISPR, CRISPR –Cas9 system for genetic engineering, CRISPR-based gene editing, gene editing on July 20, 2016| Leave a Comment »

CRISPR’s Unwanted off-target effects: Need for safety study designs with Gene-Editing

Reporter: Stephen J. Williams, Ph.D.

From CafePharma at https://www.statnews.com/2016/07/18/crispr-off-target-effects/

Do CRISPR enthusiasts have their head in the sand about the safety of gene editing?

BySHARON BEGLEY @sxbegle

JULY 18, 2016

WASHINGTON — At scientific meetings on genome-editing, you’d expect researchers to show pretty slides of the ribbony 3-D structure of the CRISPR-Cas9 molecules neatly snipping out disease-causing genes in order to, everyone hopes, cure illnesses from cancer to muscular dystrophy. Less expected: slides of someone kneeling on a beach with his head in the sand.

Yet that is what Dr. J. Keith Joung of Massachusetts General Hospital showed at the American Society of Hematology’s workshop on genome-editing last week in Washington. While the 150 experts from industry, academia, the National Institutes of Health, and the Food and Drug Administration were upbeat about the possibility of using genome-editing to treat and even cure sickle cell disease, leukemia, HIV/AIDS, and other blood disorders, there was a skunk at the picnic: an emerging concern that some enthusiastic CRISPR-ers are ignoring growing evidence that CRISPR might inadvertently alter regions of the genome other than the intended ones.

“In the early days of this field, algorithms were generated to predict off-target effects and [made] available on the web,” Joung said. Further research has shown, however, that such algorithms, including one from MIT and one calledE-CRISP, “miss a fair number” of off-target effects. “These tools are used in a lot of papers, but they really aren’t very good at predicting where there will be off-target effects,” he said. “We think we can get off-target effects to less than 1 percent, but we need to do better,” especially if genome-editing is to be safely used to treat patients.

Off-target effects occur because of how CRISPR works. It has two parts. RNA makes a beeline for the site in a genome specified by the RNA’s string of nucleotides, and an enzyme cuts the genome there. Trouble is, more than one site in a genome can have the same string of nucleotides. Scientists might address CRISPR to the genome version of 123 Main Street, aiming for 123 Main on chromosome 9, only to find CRISPR has instead gone to 123 Main on chromosome 14.

In one example Joung showed, CRISPR is supposed to edit a gene called VEGFA (which stimulates production of blood vessels, including those used by cancerous tumors) on chromosome 6. But, studies show, this CRISPR can also hit genes on virtually every one of the other 22 human chromosomes. The same is true for CRISPRs aimed at other genes. Although each CRISPR has zero to a dozen or so “known” off-target sites (where “known” means predicted by those web-based algorithms), Joung said, there can be as many as 150 “novel” off-target sites, meaning scientists had no idea those errors were possible.

One reason for concern about off-target effects is that genome-editing might disable a tumor-suppressor gene or activate a cancer-causing one. It might also allow pieces of two different chromosomes to get together, a phenomenon called translocation, which is the cause of chronic myeloid leukemia, among other problems.

Many researchers, including those planning clinical trials, are using web-based algorithms to predict which regions of the genome might get accidentally CRISPR’d. They include the scientists whose proposal to use CRISPR in patients was the first to be approved by an NIH committee. When scientists assure regulators that they looked for off-target effects in CRISPR’d cells growing in lab dishes, what they usually mean is that they looked for CRISPR’ing of genes that the algorithms flagged.

As a result, off-target effects might be occurring but, because scientists are doing the equivalent of the drunk searching for their lost keys only under the lamppost, they’re not being found.

FDA Cellular & Gene Therapy Guidances: Implications for CRSPR/Cas9 Trials

CRISPR/Cas9 Finds Its Way As an Important Tool For Drug Discovery & Development

CRISPR, the Genome Editing Technology is Nearing Human Trials: Human T cells will soon be modified using the CRISPR technique in a clinical trial to attack cancer cells

Use of CRISPR & RNAi for Drug Discovery, CHI’s World PreClinical Congress – Europe, November 14-15, 2016, Lisbon, Portugal

CRISPR: A Podcast from Nature.com on Gene Editing

AND Please See Our Following ebooks available on Amazon containing interviews with Dr. Jennifer Duodna

Volume One: Genomics Orientations for Personalized Medicine

Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS & BioInformatics, Simulations and the Genome Ontology

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Juno Therapeutics to Resume JCAR015 Phase II ROCKET Trial AND Acquires privately held Boston, MA-based RedoxTherapies

Posted in BioTechnology - Venture Creation, Venture Capital, Clinical & Translational, Clinical Genomics, FDA Regulatory Affairs, Immuno-Oncology & Genomics, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, Regulated Clinical Trials: Design, Methods, Components and IRB related issues on July 14, 2016| Leave a Comment »

Juno Therapeutics to Resume JCAR015 Phase II ROCKET Trial AND Acquires privately held Boston, MA-based RedoxTherapies

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 2/5/2018

Anatomy of a $9B buyout: Celgene’s quick turn from Juno’s close collaborator to new owner

john carroll — on February 5, 2018 05:50 AM EST

https://endpts.com/anatomy-of-a-9b-buyout-celgenes-quick-turn-from-junos-close-collaborator-to-new-owner/?utm_medium=email&utm_campaign=Monday%20February%205%202018&utm_content=Monday%20February%205%202018+CID_aecea465e79bcafc58b92d3615dfacda&utm_source=ENDPOINTS%20emails&utm_term=Anatomy%20of%20a%209B%20buyout%20Celgenes%20quick%20turn%20from%20Junos%20close%20collaborator%20to%20new%20owner

PDATED on 11/13/2017

Juno analysis of shuttered study offers clues for CAR-T

https://www.biopharmadive.com/news/juno-analysis-of-shuttered-study-offers-clues-for-car-t/510634/

UPDATED on 11/28/2016

Latest deaths in Juno trial underscore the need for greater transparency in clinical trials

quote

In recent years, numerous states have passed so-called “right-to-try” laws that encourage patients to seek access to experimental drugs outside of the clinical trial framework. In addition, libertarian activists and even some individuals associated with the incoming Trump administration continue to propose moving new medicines out into widespread use after only scant safety testing. That would increase the number of patients at risk for adverse outcomes, like the ones observed in the Juno trials, before we even know whether the drugs work.

Right-to-try laws could curtail the development of innovative new therapies

The best way to identify transformative new medicines, protect patients from unexpectedly dangerous drugs, and avoid wasting health care resources is by subjecting experimental products to well-designed clinical trials that enroll sufficient numbers of patients and test relevant clinical outcomes that can then be independently reviewed by the experts at the FDA. When severe, unanticipated problems arise, the FDA needs a transparent and systematic evaluation process that can provide public insight into what happened and why. That would contribute to the progress of science and the development of the next generation of safer, better therapies.

https://www.statnews.com/2016/11/24/deaths-juno-trial-transparency-fda/

Juno Therapeutics to Resume JCAR015 Phase II ROCKET Trial

SEATTLE–(BUSINESS WIRE)–Jul. 12, 2016– Juno Therapeutics, Inc. (Nasdaq: JUNO), a biopharmaceutical company focused on re-engaging the body’s immune system to revolutionize the treatment of cancer, today announced that the U.S. Food and Drug Administration has removed the clinical hold on the Phase II clinical trial of JCAR015 (known as the “ROCKET” trial) in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia (r/r ALL).

Under the revised protocol, the ROCKET trial will continue enrollment using JCAR015 with cyclophosphamide pre-conditioning only.

SOURCE

http://ir.junotherapeutics.com/phoenix.zhtml?c=253828&p=irol-newsArticle&ID=2184987

Juno buys early-stage biotech for access to immuno-oncology candidate

Jul 14 2016, 16:32 ET | About: Juno Therapeutics (JUNO) | By: Douglas W. House, SA News Editor

Juno Therapeutics (NASDAQ:JUNO) acquires privately held Boston, MA-based RedoxTherapies. Juno’s primary aim of the deal was to secure an exclusive license to vipadenant, a small molecule adenosine A2a receptor antagonist that may disrupt key immunosuppressive pathways in the tumor microenvironment in certain cancers.

Redox licensed vipadenant from London-based Vernalis in October 2014. It was under development for the treatment of Parkinson’s disease by Biogen (NASDAQ:BIIB) but safety concerns scuppered the effort in 2010 despite encouraging efficacy in mid-stage studies. Biogen returned the rights to Vernalis in 2011.

Under the terms of the transaction, Juno will pay $10M in upfront cash plus undisclosed milestones.

SOURCE

http://seekingalpha.com/news/3193337-juno-buys-early-stage-biotech-access-immuno-oncology-candidate?source=email_rt_mc_readmore&app=1&uprof=46#email_link

Entire Family of Impella Abiomed Impella® Therapy Left Side Heart Pumps: FDA Approved To Enable Heart Recovery

Posted in Acute Myocardial Infarction, Assist Devices: LV, CABG, Cardiac and Cardiovascular Surgical Procedures, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, congestive heart failure, FDA Regulatory Affairs, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Frontiers in Cardiology and Cardiovascular Disorders, Heart Failure (HF), Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart, Medical Devices R&D and Inventions, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, RV, tagged Cardiogenic Shock, post-cardiotomy cardiogenic shock (PCCS) on July 6, 2016| Leave a Comment »

Entire Family of Impella Abiomed Impella® Therapy Left Side Heart Pumps: FDA Approved To Enable Heart Recovery

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 11/1/2022

Johnson & Johnson to acquire Abiomed in $16.6B deal

Michael Walter | November 01, 2022 | Economics

Johnson & Johnson has entered into a definitive agreement to acquire Abiomed in a deal valued at approximately $16.6 billion. The boards of directors of both companies have unanimously approved the transaction.

Johnson & Johnson agreed to an upfront payment of $380 per share. Abiomed shareholders will also receive a non-tradeable contingent value of up to $35 per share if certain milestones are met. For example, if the company receives FDA premarket application approval for the use of its Impella heart pumps to treat ST-elevation myocardial infarction (STEMI) patients without cardiogenic shock by Jan. 1, 2028, each shareholder will receive $7.50 per share. If Impella devices receive a Class 1 recommendation for the treatment of high-risk percutaneous coronary intervention or STEMI patients with or without cardiogenic shock by Dec. 31, 2029, shareholders will receive an additional $10 per share.

“The addition of Abiomed is an important step in the execution of our strategic priorities and our vision for the new Johnson & Johnson focused on pharmaceutical and MedTech,” Johnson & Johnson CEO Joaquin Duato said in a prepared statement. “We have committed to enhancing our position in MedTech by entering high-growth segments. The addition of Abiomed provides a strategic platform to advance breakthrough treatments in cardiovascular disease and helps more patients around the world while driving value for our shareholders.”

Michael R. Minogue, Abiomed’s chairman, president and CEO, said in the same statement. “It will enable us to leverage Johnson & Johnson’s global scale, commercial strength and clinical expertise to accelerate our mission of making heart recovery the global standard of care.”

This acquisition is expected to be finalized by the end of the first quarter of 2023.

SOURCE

https://cardiovascularbusiness.com/topics/healthcare-management/healthcare-economics/johnson-johnson-acquire-abiomed-166b-deal?utm_source=newsletter&utm_medium=cvb_breaking

Abiomed Impella® Therapy Receives FDA Approval for Cardiogenic Shock After Heart Attack or Heart Surgery

Entire Family of Impella Left Side Heart Pumps FDA Approved To Enable Heart Recovery

DANVERS, Mass., April 07, 2016 (GLOBE NEWSWIRE) — Abiomed, Inc. (NASDAQ:ABMD), a leading provider of breakthrough heart support technologies, today announced that it has received U.S. Food and Drug Administration (FDA) Pre-Market Approval (PMA) for its Impella 2.5™, Impella CP®, Impella 5.0™ and Impella LD™ heart pumps to provide treatment of ongoing cardiogenic shock. In this setting, the Impella heart pumps stabilize the patient’s hemodynamics, unload the left ventricle, perfuse the end organs and allow for recovery of the native heart. This latest approval adds to the prior FDA indication of Impella 2.5 for high risk percutaneous coronary intervention (PCI), or Protected PCI™, received in March 2015.

With this approval, these are the first and only percutaneous temporary ventricular support devices that are FDA-approved as safe and effective for the cardiogenic shock indication, as stated below:

The Impella 2.5, Impella CP, Impella 5.0 and Impella LD catheters, in conjunction with the Automated Impella Controller console, are intended for short-term use (<4 days for the Impella 2.5 and Impella CP and <6 days for the Impella 5.0 and Impella LD) and indicated for the treatment of ongoing cardiogenic shock that occurs immediately (<48 hours) following acute myocardial infarction (AMI) or open heart surgery as a result of isolated left ventricular failure that is not responsive to optimal medical management and conventional treatment measures with or without an intra-aortic balloon pump. The intent of the Impella system therapy is to reduce ventricular work and to provide the circulatory support necessary to allow heart recovery and early assessment of residual myocardial function.

The product labeling also allows for the clinical decision to leave Impella 2.5, Impella CP, Impella 5.0 and Impella LD in place beyond the intended duration of four to six days due to unforeseen circumstances.

The Impella products offer the unique ability to both stabilize the patient’s hemodynamics before or during a PCI procedure and unload the heart, which allows the muscle to rest and potentially recover its native function. Heart recovery is the ideal option for a patient’s quality of life and as documented in several clinical papers, has the ability to save costs for the healthcare system^1,2,3.

Cardiogenic shock is a life-threatening condition in which the heart is suddenly unable to pump enough blood and oxygen to support the body’s vital organs. For this approval, it typically occurs during or after a heart attack or acute myocardial infarction (AMI) or cardiopulmonary bypass surgery as a result of a weakened or damaged heart muscle. Despite advancements in medical technology, critical care guidelines and interventional techniques, AMI cardiogenic shock and post-cardiotomy cardiogenic shock (PCCS) carry a high mortality risk and has shown an incremental but consistent increase in occurrence in recent years in the United States.

“This approval sets a new standard for the entire cardiovascular community as clinicians continue to seek education and new approaches to effectively treat severely ill cardiac patients with limited options and high mortality risk,” said William O’Neill, M.D., medical director of the Center for Structural Heart Disease at Henry Ford Hospital. “The Impella heart pumps offer the ability to provide percutaneous hemodynamic stability to high-risk patients in need of rapid and effective treatment by unloading the heart, perfusing the end organs and ultimately, allowing for the opportunity to recover native heart function.”

“Abiomed would like to recognize our customers, physicians, nurses, scientists, regulators and employees for their last fifteen years of circulatory support research and clinical applications. This FDA approval marks a significant milestone in the treatment of heart disease. The new medical field of heart muscle recovery has begun,” said Michael R. Minogue, President, Chairman and Chief Executive Officer of Abiomed. “Today, Abiomed only treats around 5% of this AMI cardiogenic shock patient population, which suffers one of the highest mortality risks of any patient in the heart hospital. Tomorrow, Abiomed will be able to educate and directly partner with our customers and establish appropriate protocols to improve the patient outcomes focused on native heart recovery.”

Abiomed Data Supporting FDA Approval

The data submitted to the FDA in support of the PMA included an analysis of 415 patients from the RECOVER 1 study and the U.S. Impella registry (cVAD Registry™), as well as an Impella literature review including 692 patients treated with Impella from 17 clinical studies. A safety analysis reviewed over 24,000 Impella treated patients using the FDA medical device reporting (“MDR”) database, which draws from seven years of U.S. experience with Impella.

In addition, the Company also provided a benchmark analysis of Impella patients in the real-world Impella cVAD registry vs. these same patient groups in the Abiomed AB5000/BVS 5000 Registry. The Abiomed BVS 5000 product was the first ventricular assist device (VAD) ever approved by the FDA in 1991 based on 83 patient PMA study. In 2003, the AB5000 Ventricle received FDA approval and this also included a PMA study with 60 patients.

For this approval, the data source for this benchmark analysis was a registry (“AB/BVS Registry”) that contained 2,152 patients that received the AB5000 and BVS 5000 devices, which were originally approved for heart recovery. The analysis examined by the FDA used 204 patients that received the AB5000 device for the same indications. This analysis demonstrated significantly better outcomes with Impella in these patients.

The Company believes this is the most comprehensive review ever submitted to the FDA for circulatory support in the cardiogenic shock population.

Maini B, Gregory D, Scotti DJ, Buyantseva L. Percutaneous cardiac assist devices compared with surgical hemodynamic support alternatives: Cost-Effectiveness in the Emergent Setting.Catheter Cardiovasc Interv. 2014 May 1;83(6):E183-92.
Cheung A, Danter M, Gregory D. TCT-385 Comparative Economic Outcomes in Cardiogenic Shock Patients Managed with the Minimally Invasive Impella or Extracorporeal Life Support. J Am Coll Cardiol. 2012;60(17_S):. doi:10.1016/j.jacc.2012.08.413.
Gregory D, Scotti DJ, de Lissovoy G, Palacios I, Dixon, Maini B, O’Neill W. A value-based analysis of hemodynamic support strategies for high-risk heart failure patients undergoing a percutaneous coronary intervention. Am Health Drug Benefits. 2013 Mar;6(2):88-99

ABOUT IMPELLA
Impella 2.5 received FDA PMA approval for high risk PCI in March 2015, is supported by clinical guidelines, and is reimbursed by the Centers for Medicare & Medicaid Services (CMS) under ICD-9-CM code 37.68 for multiple indications. The Impella RP® device received Humanitarian Device Exemption (HDE) approval in January 2015. The Impella product portfolio, which is comprised of Impella 2.5, Impella CP, Impella 5.0, Impella LD, and Impella RP, has supported over 35,000 patients in the United States.

The ABIOMED logo, ABIOMED, Impella, Impella CP, and Impella RP are registered trademarks of Abiomed, Inc. in the U.S.A. and certain foreign countries. Impella 2.5, Impella 5.0, Impella LD, and Protected PCI are trademarks of Abiomed, Inc.

ABOUT ABIOMED
Based in Danvers, Massachusetts, Abiomed, Inc. is a leading provider of medical devices that provide circulatory support. Our products are designed to enable the heart to rest by improving blood flow and/or performing the pumping of the heart. For additional information, please visit: www.abiomed.com

FORWARD-LOOKING STATEMENTS
This release includes forward-looking statements. These forward-looking statements generally can be identified by the use of words such as “anticipate,” “expect,” “plan,” “could,” “may,” “will,” “believe,” “estimate,” “forecast,” “goal,” “project,” and other words of similar meaning. These forward-looking statements address various matters including, the Company’s guidance for fiscal 2016 revenue. Each forward-looking statement contained in this press release is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others, uncertainties associated with development, testing and related regulatory approvals, including the potential for future losses, complex manufacturing, high quality requirements, dependence on limited sources of supply, competition, technological change, government regulation, litigation matters, future capital needs and uncertainty of additional financing, and the risks identified under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended March 31, 2015 and the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2015, each filed with the Securities and Exchange Commission, as well as other information the Company files with the SEC. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at www.sec.gov, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this release and the Company undertakes no obligation to update or revise any of these statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.

For more information, please contact: Aimee Genzler Director, Corporate Communications 978-646-1553 agenzler@abiomed.com Ingrid Goldberg Director, Investor Relations igoldberg@abiomed.com

SOURCE
http://investors.abiomed.com/releasedetail.cfm?ReleaseID=964113

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Archive for the ‘FDA Regulatory Affairs’ Category

21st Century Cures Act reforms to the Food and Drug Administration’s (FDA) regulation of the medical device and pharmaceutical industries – Medical Device Overview: Major FDA Reform Bill Becomes Law

A copy of the act can be found here.

Other related articles published in this Open Access Online Scientific Journal include the following:

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Artificial Pancreas – Medtronic Receives FDA Approval for World’s First Hybrid Closed Loop System for People with Type 1 Diabetes

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UPDATED Postmarketing Safety or Effectiveness Data Needed: The 2013 paper was funded by the firm Sarepta Therapeutics, sellers of eteplirsen, a surge in its shares seen after the approval. Eteplirsen will cost patients around $300,000 a year.

FDA advisers narrowly vote in favor of Sarepta’s DMD gene therapy

Sarepta Duchenne drug rejected by FDA in surprise setback

Dive Brief:

Factors at play for FDA Approval of eteplirsen

FDA grants accelerated approval to first drug for Duchenne muscular dystrophy

The viability of this drug approval depends on “to be gathered” Postmarketing safety or effectiveness data, aka follow-up confirmatory trials.

Sarepta CEO Ed Kaye on FDA courage, NICE and resilience

Need for follow-up confirmatory trials remains outstanding

FDA’s Postmarketing Surveillance Programs

FDA’s Regulations and Policies and Procedures for Postmarketing Surveillance Programs

Positions on Sarepta’s eteplirsen Scientific Approach

Gene Editing for Exon 51: Why CRISPR Snipping might be better than Exon Skipping for DMD

Related Resources on FDA’s Policies on Drugs:

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“I’m expecting a flood of trials to get registered,” FDA Commissioner Robert Califf

Biden threatens funding cuts for researchers who fail to report clinical trial results

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Roche’s I-O drug Tecentriq picks up key first-in-class breast cancer nod

Dive Insight:

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Merck increases grip on its lead in lung cancer, winning approval for Keytruda/chemo combo as first-line therapy

Roche’s shocking Tecentriq fail raises red flag for bladder cancer rivals

World’s Top Ten Cancer Drugs by 2020 (million USD)

For a review of all the complexities involved in the emerging market for BioMarkers in Immuno-Therapy, see

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Genomics Orientations for Personalized Medicine

Volume One

electronic Table of Contents

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Thriving Three Groups on LinkedIn

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CRISPR’s Unwanted off-target effects: Need for safety study designs with Gene-Editing

Do CRISPR enthusiasts have their head in the sand about the safety of gene editing?

Other articles on CRISPR and Gene Editing on this Open Access Journal Include:

AND Please See Our Following ebooks available on Amazon containing interviews with Dr. Jennifer Duodna

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Juno Therapeutics to Resume JCAR015 Phase II ROCKET Trial AND Acquires privately held Boston, MA-based RedoxTherapies

Juno analysis of shuttered study offers clues for CAR-T

Latest deaths in Juno trial underscore the need for greater transparency in clinical trials

Juno Therapeutics to Resume JCAR015 Phase II ROCKET Trial

Juno buys early-stage biotech for access to immuno-oncology candidate

Other related articles published in this open Access Online Scientific Journal include the following:

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Entire Family of Impella Abiomed Impella® Therapy Left Side Heart Pumps: FDA Approved To Enable Heart Recovery

Johnson & Johnson to acquire Abiomed in $16.6B deal

Abiomed Impella® Therapy Receives FDA Approval for Cardiogenic Shock After Heart Attack or Heart Surgery

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