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As BioMed e-Series Editor–in-Chief, Aviva Lev-Ari, PhD, RN was responsible for

· All the documentation (Instruction manuals) on Style setting, and for

· Training all team members

· Journal Articles Format

· Journal Comment Exchange Format

· e-Books Production Process:

1. Volume creation from Journal’s Article Archive,

2. Format Translation from HTML to .mobi for Kindle devices,

3. Proof reading process,

4. Title release,

5. Book electronic Upload to Amazon.com Cloud.

6. Connection of all articles and e-Books to Social Media, Ping back generation by mentioning other related articles published in the Journal

Lastly, 6, below

Title	Date of Publication	Number of Pages
Perspectives on Nitric Oxide in Disease Mechanisms	6/21/2013	895
Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation	11/30/2015	11039 KB
Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics	11/29/2015	12333 KB
Regenerative and Translational Medicine: The Therapeutics Promise for Cardiovascular Diseases	12/26/2015	11668 KB
Genomics Orientations for Personalized Medicine	11/23/2015	11724 KB
Cancer Biology & Genomics for Disease Diagnosis	8/11/2015	13744 KB
Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery	5/18/2017	5408 pages
Metabolic Genomics and Pharmaceutics	7/21/2015	13927 KB
The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications	9/4/2017	3747 pages
The VOICES of Patients, Hospitals CEOs, Health Care Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures	10/16/2017	826 pages
Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders	12/9/2017	2862 pages
Milestones in Physiology: Discoveries in Medicine, Genomics and Therapeutics	12/27/2015	11125 KB
Medical 3D BioPrinting – The Revolution in Medicine, Technologies for Patient-centered Medicine: From R&D in Biologics to New Medical Devices	12/30/2017	1005 pages
Pharmacological Agents in Treatment of Cardiovascular Disease	Work-in-Progress, Expected Publishing date in 2018	???
Interventional Cardiology and Cardiac Surgery for Disease Diagnosis and Guidance of Treatment	Work-in-Progress, Expected Publishing date in 2018	???

https://www.nih.gov/news-events/news-releases/human-genome-project-awarded-thai-2017-prince-mahidol-award-field-medicine

Posted in Affordable Care Act, Award Nominations, BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceuticall R&D Informatics, Clinical Genomics, Cancer Informatics, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Medical and Population Genetics, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, tagged 2017 Prince Mahidol Award, advances in the field of medicine, disease diagnosis, Human Genome Project, NHGRI, NIH, prevention, treatment on February 9, 2018| Leave a Comment »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

The Thai royal family awarded its annual prizes in Bangkok, Thailand, in late January 2018 in recognition of advances in public health and medicine – through the Prince Mahidol Award Foundation under the Royal Patronage. This foundation was established in 1992 to honor the late Prince Mahidol of Songkla, the Royal Father of His Majesty King Bhumibol Adulyadej of Thailand and the Royal Grandfather of the present King. Prince Mahidol is celebrated worldwide as the father of modern medicine and public health in Thailand.

The Human Genome Project has been awarded the 2017 Prince Mahidol Award for revolutionary advances in the field of medicine. The Human Genome Project was completed in 2003. It was an international, collaborative research program aimed at the complete mapping and sequencing of the human genome. Its final goal was to provide researchers with fundamental information about the human genome and powerful tools for understanding the genetic factors in human disease, paving the way for new strategies for disease diagnosis, treatment and prevention.

The resulting human genome sequence has provided a foundation on which researchers and clinicians now tackle increasingly complex problems, transforming the study of human biology and disease. Particularly it is satisfying that it has given the researchers the ability to begin using genomics to improve approaches for diagnosing and treating human disease thereby beginning the era of genomic medicine.

National Human Genome Research Institute (NHGRI) is devoted to advancing health through genome research. The institute led National Institutes of Health’s (NIH’s) contribution to the Human Genome Project, which was successfully completed in 2003 ahead of schedule and under budget. NIH, is USA’s national medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases.

Building on the foundation laid by the sequencing of the human genome, NHGRI’s work now encompasses a broad range of research aimed at expanding understanding of human biology and improving human health. In addition, a critical part of NHGRI’s mission continues to be the study of the ethical, legal and social implications of genome research.

References:

http://www.mfa.go.th/main/en/news3/6886/83875-Announcement-of-the-Prince-Mahidol-Laureates-2017.html

http://www.thaiembassy.org/london/en/news/7519/83884-Announcement-of-the-Prince-Mahidol-Laureates-2017.html

http://englishnews.thaipbs.or.th/us-human-genome-project-influenza-researchers-win-prince-mahidol-award-2017/

http://genomesequencing.com/the-human-genome-project-is-awarded-the-thai-2017-prince-mahidol-award-for-the-field-of-medicine-national-institutes-of-health-press-release/

This Pioneering $475,000 Cancer Drug Comes With A Money-Back Guarantee

Posted in Drug Delivery Platform Technology, Drug Development Process, Drug Discovery Chemistry, Patient-centered Medicine, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmaceuticall R&D Informatics, Pharmacogenomics, Value-based Drug Pricing on August 31, 2017| Leave a Comment »

Curator: Aviva Lev-Ari, PhD, RN

UPDATED on 9/1/2017:

Novartis defends the eye-popping price of its pioneering gene therapy with arguments about its $1 billion expenditure—and novel “value-based” pricing.

https://www.fastcompany.com/40461214/how-novartis-is-defending-the-record-475000-price-of-its-pioneering-gene-therapy-cancer-drug-car-t-kymriah

On 8/30/2017 we wrote:

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2017/08/30/fda-has-approved-the-worlds-first-car-t-therapy-novartis-for-kymriah-tisagenlecleucel-and-gileads-12-billion-buy-of-kite-pharma-no-approved-drug-and-canakinumab-for-lung-cancer-may-be/

The Price for the Treatment was published on 8/31/2017, a Value-based Pricing Payment Model of a $475,000 per patient charge for the responding patients after ONE month of treatment. Novartis says it takes an average of 22 days to create the therapy, from the time a patient’s cells are removed to when they are infused back into the patient. Kymriah will initially be available at 20 U.S. hospitals within a month, Novartis says. Eventually, 32 total sites will offer the therapy.

CAR-T gained national attention three years ago when Carl June, a researcher at the University of Pennsylvania, used to put a young girl’s acute lymphoblastic leukemia. Genetically altering the girl’s immune cells had made her deathly ill, but June had used a Roche drug, Actemra, to treat the side effects. She lived, and the results were published in The New England Journal of Medicine. Novartis bought the rights to the Penn treatment for just $20 million up front.

Pharma Buying the right to use from an Academic Institution is a known route to leap frog the R&D lengthy process of Drug discovery.

“I’ve told the team that resources are not an issue. Speed is the issue,” says Novartis’ Chief Executive Joseph Jimenez, told Forbes in a cover story about the work then.

The FDA calls this CAR-T therapy treatment, made by Novartis, the “first gene therapy” in the U.S. The therapy is designed to treat an often-lethal type of blood and bone marrow cancer that affects children and young adults. The FDA defines gene therapy as a medicine that “introduces genetic material into a person’s DNA to replace faulty or missing genetic material” to treat a disease or medical condition. This is the first such therapy to be available in the U.S., according to the FDA.

Two gene therapies for rare, inherited diseases have already been approved in Europe.

To further evaluate the long-term safety, Novartis is also required to conduct a post-marketing observational study involving patients treated with Kymriah.

The FDA granted Kymriah Priority Review and Breakthrough Therapy designations. The Kymriah application was reviewed using a coordinated, cross-agency approach. The clinical review was coordinated by the FDA’s Oncology Center of Excellence, while CBER conducted all other aspects of review and made the final product approval determination.

The FDA granted approval of Kymriah to Novartis Pharmaceuticals Corp. The FDA granted the expanded approval of Actemra to Genentech Inc.

FDA commissioner Scott Gottlieb in a statement.

“We’re entering a new frontier in medical innovation with the ability to reprogram a patient’s own cells to attack a deadly cancer,”

“Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). “Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials.”

https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm

The Protocol

A patient’s T cells are extracted and cryogenically frozen so that they can be transported to Novartis’s manufacturing center in New Jersey. There, the cells are genetically altered to have a new gene that codes for a protein—called a chimeric antigen receptor, or CAR. This protein directs the T cells to target and kill leukemia cells with a specific antigen on their surface. The genetically modified cells are then infused back into the patient.

In a clinical trial of 63 children and young adults with a type of acute lymphoblastic leukemia, 83 percent of patients that received the CAR-T therapy had their cancers go into remission within three months. At six months, 89 percent of patients who received the therapy were still living, and at 12 months, 79 percent had survived.

https://www.technologyreview.com/s/608771/the-fda-has-approved-the-first-gene-therapy-for-cancer/?utm_campaign=add_this&utm_source=email&utm_medium=post

Similar CAR-T treatments were being developed at other institutions including
Memorial Sloan-Kettering Cancer Center,
Seattle Children’s Hospital, and
The National Cancer Institute.
The Memorial and Seattle work was spun off into a startup called Juno Therapeutics, which has fallen behind. Juno Therapeutics ended a CAR-T study earlier this year after patients died from cerebral edema, or swelling in the brain.
The NCI work became the basis for the product being developed by Kite Pharma. Kite Pharma, which is awaiting FDA approval for its CAR-T therapy to treat a form of blood cancer in adults, was this week bought out by Gilead in a deal worth $11.9 billion.

On Cambridge Healthtech Institute’s 4th Annual Adoptive T Cell Therapy, Delivering CAR, TCR, and TIL from Research to Reality, August 29 – 30, 2017 | Sheraton Boston | Boston, MA

TUESDAY, AUGUST 29 – I covered in Real Time the talk on Juno Therapeutics: Building Better T Cell Therapies: The Power of Molecular Profiling by Mark Bonyhadi, Ph.D., Head, Research and Academic Affairs, Juno Therapeutics

https://pharmaceuticalintelligence.com/2017/08/29/live-829-chis-oncolytic-virus-immunotherapy-and-adoptive-cell-therapy-august-28-29-2017-sheraton-boston-hotel-boston-ma/

All of the CAR-T products are expensive to make, and must be manufactured on an individual basis for each new patient from the patient’s own T-cells, a type of white blood cells, a process that takes weeks.

How quickly companies can speed up manufacturing.

Kymriah will be manufactured at a facility in Morris Plains, N.J.

CAR-T technology, which has so far been used only in patients with blood cancers that have not been cured by other treatments, can be used earlier in the disease or for solid tumors: Breast, Prostate, Melanomas.

https://www.forbes.com/sites/matthewherper/2017/08/30/fda-approves-novartis-treatment-that-alters-patients-cells-to-fight-cancer/#2aecb25b4400

https://www.technologyreview.com/s/608666/a-cancer-atlas-to-predict-how-patients-will-fare/?set=

Modeling the cancer transcriptome

Recent initiatives such as The Cancer Genome Atlas have mapped the genome-wide effect of individual genes on tumor growth. By unraveling genomic alterations in tumors, molecular subtypes of cancers have been identified, which is improving patient diagnostics and treatment. Uhlen et al. developed a computer-based modeling approach to examine different cancer types in nearly 8000 patients. They provide an open-access resource for exploring how the expression of specific genes influences patient survival in 17 different types of cancer. More than 900,000 patient survival profiles are available, including for tumors of colon, prostate, lung, and breast origin. This interactive data set can also be used to generate personalized patient models to predict how metabolic changes can influence tumor growth.

https://www.forbes.com/sites/stephenbrozak/2017/08/30/gilead-kite-a-new-transformative-deal-and-maybe-the-new-future-of-healthcare-deals/#fc64fca65d49

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, CAR-T, Drug Development Process, Drug Discovery Chemistry, Immuno-Oncology & Genomics, Immunotherapy, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmacogenomics on August 30, 2017| Leave a Comment »

Curator: Aviva Lev-Ari, PhD, RN

UPDATED on 9/7/2017

Here’s the inside account of Gilead’s 11-week sprint to its $12B Kite buyout – ENDPOINTS NEWS

UPDATED on 8/31/2017

Gilead-Kite: A New Transformative Deal For Biotech, AUG 30, 2017

Gilead has made a big bet on new technology in Kite’s immunotherapy platforms and has reduced the number of credible large players in the space.

With a reputation for intense diligence and dynamism in its business development efforts, Gilead’s management team will only bolster the immunotherapy field as it prepares to face off with Novartis, its immediate competitor, and enters squarely in the province of Merck and Bristol Myers Squibb, two of the leaders in immuno-oncology.

Gilead has reinvented the transformative transaction for the sector.

I attended this week the Cambridge Healthtech Institute’s 4th Annual

Delivering CAR, TCR, and TIL from Research to Reality
August 29 – 30, 2017 | Sheraton Boston | Boston, MA

The following talks on 8/29/2017 presented the frontier of CAR-T Therapies and Technologies from lab to bed side:

Building Better T Cell Therapies: The Power of Molecular Profiling

Mark Bonyhadi, Ph.D., Head, Research and Academic Affairs, Juno Therapeutics

Tricked-Out Cars, the Next Generation of CAR T Cells

Richard Morgan, Ph.D., Vice President, Immunotherapy, Bluebird Bio

The Generation of Lentiviral Vector-Modified CAR-T Cells Using an Automated Process

Boro Dropulic, Ph.D., General Manager and CSO, Lentigen Technology, Inc.

I covered this event in Real Time for the Press

LIVE – 8/29 – CHI’s Oncolytic Virus Immunotherapy and ADOPTIVE CELL THERAPY, August 28-29, 2017 Sheraton Boston Hotel | Boston, MA

https://pharmaceuticalintelligence.com/2017/08/29/live-829-chis-oncolytic-virus-immunotherapy-and-adoptive-cell-therapy-august-28-29-2017-sheraton-boston-hotel-boston-ma/

What does this mean for Immunotherapy? FDA put a temporary hold on Juno’s JCAR015, Three Death of Celebral Edema in CAR-T Clinical Trial and Kite Pharma announced Phase II portion of its CAR-T ZUMA-1 trial

https://pharmaceuticalintelligence.com/2016/07/09/what-does-this-mean-for-immunotherapy-fda-put-a-temporary-hold-on-jcar015-three-death-of-celebral-edema-in-car-t-clinical-trial-and-kite-pharma-announced-phase-ii-portion-of-its-car-t-zuma-1-trial/

Lydia Ramsey reported on Aug. 28, 2017 that Gilead just handed a revolutionary kind of cancer treatment a $12 billion endorsement.

For Gilead, which is known for its HIV and hepatitis C medications, this is an entirely new area of cancer development.

“The field of cell therapy has advanced very quickly, to the point where the science and technology have opened a clear path toward a potential cure for patients,” Gilead CEO John Milligan said in a news release. “We are greatly impressed with the Kite team and what they have accomplished, and share their belief that cell therapy will be the cornerstone of treating cancer.”

In July, a Food and Drug Administration panel voted in favor of approving one of these treatments made by Novartis. One of the panelists called it “most exciting thing I’ve seen in my lifetime.” The FDA is expected to decide whether to approve that therapy, a treatment for pediatric acute lymphoblastic lymphoblastic leukemia, by October.

Gilead won’t have to wait long to see if the FDA will approve Kite’s leading cell therapy, which is called axicabtagene ciloleucel or axi-cel. In November, Kite is expected to get an answer from the FDA regarding its CAR-T treatment for a type of blood cancer called aggressive B-cell non-Hodgkin lymphoma. In data Kite released in February, the company found that out of 101 patients, 36% had a complete response to the treatment after six months.

The one-time treatments won’t come cheap. While companies might price the drug based on how well it works, axi-cel’s price tag could still be $325,000. Analysts expect the therapy to generate $1.7 billion in sales by 2022.

While its axi-cel program is the farthest along, Kite’s also working on another CAR-T cell therapy that’s in clinical trials to treat multiple myeloma, another form of blood cancer. The company’s also working on cell therapies to treat solid tumors that are still in early clinical trials.

On August 30, 2017, John Carroll writes:

[A]pproval marks a major shift in oncology, with a truly revolutionary approach to treating cancer.

The FDA has approved the world’s first CAR-T therapy, giving a green light to Novartis for Kymriah (tisagenlecleucel) in what regulators themselves describe as an historic event.

The accelerated approval — about a month ahead of the PDUFA date — came through for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia

Novartis, the leader in the field, which will set the price on this therapy and likely those to come. Novartis’ investigators registered a game-changing 83% remission rate in its pivotal study.

CAR-T, though, is also associated with severe and potentially deadly side effects, including lethal instances of cytokine release syndrome with some patients dying from brain swelling in separate studies from the Novartis drug.

Regulators noted that they will require special training for anyone involved in delivering this therapy, while expanding the approval of Actemra (tocilizumab) to treat CAR T-cell-induced severe or life-threatening CRS in patients 2 years of age or older. “In clinical trials in patients treated with CAR-T cells,” the FDA reported, “69% of patients had complete resolution of CRS within two weeks following one or two doses of Actemra.”

Said Joseph Jimenez, CEO of Novartis:

“Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care.”

This approval marks a major shift in oncology, with a truly revolutionary approach to treating cancer. That hasn’t escaped the notice of big players and small, with a host of developers looking to do much better, more safely, with new drugs in the pipeline.

SOURCE

From: “John Carroll [Endpoints News]” <john@endpointsnews.com>

Reply-To: <john@endpointsnews.com>

Date: Wednesday, August 30, 2017 at 11:27 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: BREAKING: FDA ushers in a new era in cancer treatment with ‘historic’ CAR-T approval for Novartis

When researchers looked at the safety profile of canakinumab, they found something amazing — a major reduction in the risk of fatal cancers. This was driven by an effect of the highest dose of the drug to prevent lung cancer. The 300 mg dose reduced the occurrence of lung cancer by 67% and death from lung cancer by 77%. It was Viagra all over again.

SOURCE

Is Canakinumab the Next Viagra?

In this Revolution and Revelation, Milton Packer explains how safety data can sometimes trump a primary endpoint

by Milton PackerAugust 30, 2017

https://www.medpagetoday.com/Blogs/RevolutionandRevelation/67605

Posted in DNA repair, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Genomic Testing: Methodology for Diagnosis, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics on July 10, 2017| Leave a Comment »

Guest Author: David Davenport, Office Administrator, Personalized Medicine Coalition

“Health care today is reactive and costly … anything but personalized … but we are now entering a new era where health care is becoming proactive, preventive, highly personalized and most importantly predictive,” said J. Craig Venter, Ph.D., Founder, President, CEO, J. Craig Venter Institute, during his opening keynote at the Personalized Medicine and Diagnostics Track at the 2017 BIO International Convention in San Diego from June 21 – 22. The track, co-organized by PMC, brought together thought leaders to discuss breakthroughs in advancing personalized medicine. From those conversations several themes emerged:

Complex genetic data require a “knowledge network” to translate into personalized care.

During the session titled The Next Frontier: Navigating Clinical Adoption of Personalized Medicine, moderated by PMC Vice President for Science Policy Daryl Pritchard, Ph.D., panelists discussed how to accelerate the clinical adoption of innovative personalized therapies. Jennifer Levin Carter, M.D., Founder and Chief Medical Officer of N-of-One, a clinical diagnostic testing interpretation service company, explained that as data grows in complexity, there is a growing need for partnerships to efficiently analyze the data and develop effective targeted treatment plans. India Hook-Barnard, Ph.D., Director of Research Strategy, Associate Director of Precision Medicine, University of California, San Francisco (UCSF), agreed and discussed the need to build a “knowledge network” that can harness data and expertise to inform provider-patient decision-making.

Discussing how personalized medicine can be integrated into community health centers lacking large research budgets, Lynn Dressler, Dr.P.H., Director of Personalized Medicine and Pharmacogenomics at Mission Health Systems, a rural community health care delivery system in Asheville, North Carolina, discussed the need to better educate physicians and patients as well as the role that a knowledge network could play in providing easy and cost-effective access to diagnostic testing services.

Delivering personalized medicine requires innovative partnerships involving industry, IT companies, providers, payers and the government.

During It’s a Converging World: Innovative Partnerships and Precision Medicine, a panel moderated by Kristin Pothier, Global Head of Life Sciences Strategy, Ernst & Young, discussed the need for “open data” where improved patient care is the shared goal, and how public-private partnerships that address education, evidence development and access to care can help foster personalized medicine.

During a session titled Nevada as a New Model for Population Health Study, Nevada-based health system Renown Health outlined a study in which it partnered with genetic testing company 23andMe to examine whether free access to genetic testing changes participants’ practices in managing their own health and facilitates the utilization of personalized medicine.

In the era of personalized medicine, measuring and delivering value requires a paradigm shift from population-based to individual-based evidence.

Following a discussion on regulatory and reimbursement challenges moderated by Bruce Quinn, M.D., Ph.D., Principal, Bruce Quinn Associates, during which panelists called for the simplification of payment structures to be more consistent, more efficient and more connected to the patient market, a panel moderated by Jennifer Snow, Director of Health Policy at Xcenda, discussed how value assessment frameworks must adapt to consider the value of personalized medicine. During The Whole Picture: Consideration of Personalized Medicine in Value Assessment Frameworks, panelist Mitch Higashi, Ph.D., Vice President, Health Economics and Outcomes Research, U.S., Bristol-Myers Squibb, called for patient-centered definitions of value and advocated for the inclusion of predictive biomarkers in all value frameworks. Donna Cryer, J.D., President, CEO, Global Liver Institute, added that the “patient must be the ultimate ‘arbiter of value’” and urged “transparency” in how value assessment frameworks are used.

Noting that different assessment frameworks have different goals, Roger Longman, CEO, Real Endpoints, called for more dynamic frameworks that allow different stakeholders to “use the same criteria but weigh them differently.” The panel concluded that to advance personalized medicine, value frameworks must be meaningful, practical and predictive for patients; reflect evolving evidence needs like real-world evidence; and consider breakthrough payment structures like bundled payments.

From Promise to Practice: The Way Forward for Personalized Medicine

During the concluding session, Creating a Universal Biomarker Program, moderated by Ian Wright, Owner, Strategic Innovations LLC, on behalf of Cedars-Sinai Precision Health, panelists discussed how to make patients the point of reference for their own care, as opposed to being compared to the “normal” range of population averages in treatment decisions using biomarkers. The speakers concluded that moving in that direction requires providers to establish baselines for each patient, along with tools and metrics to facilitate the approach.

In the words of Donna Cryer, “personalized medicine is the definition of value for a patient.” With the ability to detect diseases before they even express themselves, the promise of personalized medicine has never been greater.

However, changing the health care system to improve patient access to valuable personalized medicines requires innovation and collaboration. As PMC President Edward Abrahams, Ph.D., said during his opening remarks for the track, that change

“doesn’t come easily,” but “breakthrough” discussions like these continue to move us forward.

The complete track agenda can be downloaded here.

SOURCE

From: <pmc@personalizedmedicinecoalition.org>

Date: Monday, July 10, 2017 at 10:51 AM

To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>

Subject: Breakthroughs From the 2017 BIO Convention’s PM & Dx Track

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

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 »

Curator: Aviva Lev-Ari, PhD, RN

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.

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

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

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.

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

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

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

Tracking retractions as a window into the scientific process

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/