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19 of the 49 New Therapeutic Molecular Entities FDA approved in 2020 — as well as a new Cell-based therapy — are Personalized Medicines

Reporter: Aviva Lev-Ari, PhD, RN

 

2020 DRUG APPROVALS

19 of the 49 new therapeutic molecular entities FDA approved in 2020 — as well as a new cell-based therapy — are personalized medicines.

Newly Approved Therapeutic Molecular Entities

1. Ayvakit (avapritinib) — for the treatment of metastatic gastrointestinal stromal tumor (GIST). The decision to use this product is informed by the PDGFRA exon 18 biomarker status in the tumors of patients.

2. Nexletol (bempedoic acid) — for the treatment of adults with familial hypercholesterolemia who require additional lowering of LDL-C. The use of this product can be informed by the FH biomarker (LOLR, APOB, PCSK9) status in patients.

3. Tukysa (tucatinib) — for the treatment of metastatic breast cancer. The decision to use this product is informed by the HER2 biomarker status in the tumors of patients.

4. Pemazyre (pemigatinib) — for the treatment of cholangiocarcinoma. The decision to use this product is informed by the FGFR2 biomarker status in the tumors of patients.

5. Trodelvy (sacituzumab govitecan-hziy) — for the treatment of metastatic triple-negative breast cancer. The decision to use this product is informed by the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) biomarker statuses in the tumors of patients. Personalized Medicine at FDA 7

6. Tabrecta (capmatinib) — for the treatment of non-small cell lung cancer (NSCLC). The decision to use this product is informed by the MET exon 14 biomarker status in the tumors of patients.

7. Retevmo (selpercatinib) — for the treatment of lung and thyroid cancers. The decision to use this product is informed by the RET fusion biomarker status in the tumors of patients.

8. Uplizna (inebilizumab-cdon) — for the treatment of neuromyelitis optica spectrum disorder. The decision to use this product is informed by the AQP4 biomarker status in patients.

9. Rukobia (fostemsavir) — for the treatment of human immunodeficiency virus (HIV) infection in adults with multidrug-resistant HIV-1 infection. The use of this product can be informed by the HIV-1 expression levels in patients.

10. Evrysdi (risdiplam) — for the treatment of spinal muscular atrophy. This product selectively targets the SMN2 biomarker in patients.

11. Olinvyk (oliceridine) — for the management of acute pain. The use of this product can be informed by the CYP2D6 biomarker status in patients.

12. Viltepso (viltolarsen) — for the treatment of Duchenne muscular dystrophy. This product selectively targets, and its use is informed by, the DMD gene exon 53 biomarker in patients.

13. Enspryng (satralizumab-mwge) — for the treatment of neuromyelitis optica spectrum disorder. The decision to use this product is informed by the AQP4 biomarker status in patients.

14. Gavreto (pralsetinib) — for the treatment of non-small cell lung cancer (NSCLC). The decision to use this product is informed by the RET fusion biomarker status in the tumors of patients.

15. Zokinvy (lonafarnib) — for the treatment of progeroid laminopathies. The decision to use this product is informed by the LMN4 and/or ZMPSTE24 biomarker statuses in patients. 8 Personalized Medicine at FDA Methodology: When evaluating new molecular entities, PMC defined personalized medicines as those therapeutic products for which the label includes reference to specific biological markers, often identified by diagnostic tools, that help guide decisions and/or procedures for their use in individual patients.

16. Oxlumo (lumasiran) — for the treatment of hyperoxaluria type 1. This product selectively targets the hydroxy acid oxidase 1 (HAO1) biomarker in patients.

17. Imcivree (setmelanotide) — for the treatment of obesity due to pro-opiomelanocortin (POMC) deficiency. The decision to use this product is informed by the POMC, PCSK1, or LEPR biomarker statuses in patients.

18. Orladeyo (berotralstat) — for the treatment of hereditary angioedema types I and II. The use of this product can be informed by the C1-INH biomarker status in patients.

19. Margenza (margetuximab-cmkb) — for the treatment of breast cancer. The decision to use this product is informed by the human epidermal growth factor receptor 2 (HER2) biomarker status in the tumors of patients. Newly Approved Cell-Based Therapy

20. Tecartus (brexucabtagene autoleucel) — for the treatment of mantle cell lymphoma (MCL). The treatment is a fully integrated CD19-directed genetically modified autologous T-cell immunotherapy indicated for the treatment of adult patients with refractory MCL.

 

SOURCE

https://mma.prnewswire.com/media/1436855/PM_at_FDA_The_Scope_Significance_of_Progress_in_2020.pdf?p=pdf


Happy 80th Birthday: Radioiodine (RAI) Theranostics: Collaboration between Physics and Medicine, the Utilization of Radionuclides to Diagnose and Treat: Radiation Dosimetry by Discoverer Dr. Saul Hertz, the early history of RAI in diagnosing and treating Thyroid diseases and Theranostics

 

Guest Author: Barbara Hertz

 203-661-0777

htziev@aol.com

Celebrating eighty years of radionuclide therapy and the work of Saul Hertz

First published: 03 February 2021

Both authors contributed to the development, drafting and final editing of this manuscript and are responsible for its content.

Abstract

March 2021 will mark the eightieth anniversary of targeted radionuclide therapy, recognizing the first use of radioactive iodine to treat thyroid disease by Dr. Saul Hertz on March 31, 1941. The breakthrough of Dr. Hertz and collaborator physicist Arthur Roberts was made possible by rapid developments in the fields of physics and medicine in the early twentieth century. Although diseases of the thyroid gland had been described for centuries, the role of iodine in thyroid physiology had been elucidated only in the prior few decades. After the discovery of radioactivity by Henri Becquerel in 1897, rapid advancements in the field, including artificial production of radioactive isotopes, were made in the subsequent decades. Finally, the diagnostic and therapeutic use of radioactive iodine was based on the tracer principal that was developed by George de Hevesy. In the context of these advancements, Hertz was able to conceive the potential of using of radioactive iodine to treat thyroid diseases. Working with Dr. Roberts, he obtained the experimental data and implemented it in the clinical setting. Radioiodine therapy continues to be a mainstay of therapy for hyperthyroidism and thyroid cancer. However, Hertz struggled to gain recognition for his accomplishments and to continue his work and, with his early death in 1950, his contributions have often been overlooked until recently. The work of Hertz and others provided a foundation for the introduction of other radionuclide therapies and for the development of the concept of theranostics.

SOURCE

https://aapm.onlinelibrary.wiley.com/doi/full/10.1002/acm2.13175

 

 

SOURCE

https://www.youtube.com/watch?v=34Qhm8CeMuc

 

http://www.wjnm.org/article.asp?issn=1450-1147;year=…

http://www.wjnm.org/text.asp?2019/18/1/8/250309

Abstract

Dr. Saul Hertz was Director of The Massachusetts General Hospital’s Thyroid Unit, when he heard about the development of artificial radioactivity. He conceived and brought from bench to bedside the successful use of radioiodine (RAI) to diagnose and treat thyroid diseases. Thus was born the science of theragnostics used today for neuroendocrine tumors and prostate cancer. Dr. Hertz’s work set the foundation of targeted precision medicine.

Keywords: Dr. Saul Hertz, nuclear medicine, radioiodine

 

How to cite this article:
Hertz B. A tribute to Dr. Saul Hertz: The discovery of the medical uses of radioiodine. World J Nucl Med 2019;18:8-12

 

How to cite this URL:
Hertz B. A tribute to Dr. Saul Hertz: The discovery of the medical uses of radioiodine. World J Nucl Med [serial online] 2019 [cited 2021 Mar 2];18:8-12. Available from: http://www.wjnm.org/text.asp?2019/18/1/8/250309

 

 

  • Dr Saul Hertz (1905-1950) discovers the medical uses of radioiodine

Barbara Hertz, Pushan Bharadwaj, Bennett Greenspan»

Abstract » PDF» doi: 10.24911/PJNMed.175-1582813482

 

SOURCE

http://saulhertzmd.com/home

 

  • Happy 80th Birthday: Radioiodine (RAI) Theranostics

Thyroid practitioners and patients are acutely aware of the enormous benefit nuclear medicine has made to mankind. This month we celebrate the 80th anniversary of the early use of radioiodine(RAI).

Dr. Saul Hertz predicted that radionuclides “…would hold the key to the larger problem of cancer in general,” and may just be the best hope for diagnosing and treating cancer successfully.  Yes, RAI has been used for decades to diagnose and treat disease.  Today’s “theranostics,” a term that is a combination of “therapy” and “diagnosis” is utilized in the treatment of thyroid disease and cancer. 

            This short note is to celebrate Dr. Saul Hertz who conceived and brought from bench to bedside the medical uses of RAI; then in the form of 25 minute iodine-128.  

On March 31st 1941, Massachusetts General Hospital’s Dr. Saul Hertz (1905-1950) administered the first therapeutic use of Massachusetts Institute of Technology (MIT) cyclotron produced RAI.  This landmark case was the first in Hertz’s clinical studies conducted with MIT, physicist Arthur Roberts, Ph.D.

[Photo – Courtesy of Dr Saul Hertz Archives ]

Dr Saul Hertz demonstrating RAI Uptake Testing

            Dr. Hertz’s research and successful utilization of radionuclides to diagnose and treat diseases and conditions, established the use of radiation dosimetry and the collaboration between physics and medicine and other significant practices.   Sadly, Saul Hertz (a WWII veteran) died at a very young age.  

 

About Dr. Saul Hertz

Dr. Saul Hertz (1905 – 1950) discovered the medical uses of radionuclides.  His breakthrough work with radioactive iodine (RAI) created a dynamic paradigym change integrating the sciences.  Radioactive iodine (RAI) is the first and Gold Standard of targeted cancer therapies.  Saul Hertz’s research documents Hertz as the first and foremost person to conceive and develop the experimental data on RAI and apply it in the clinical setting.

Dr. Hertz was born to Orthodox Jewish immigrant parents in Cleveland, Ohio on April 20, 1905. He received his A.B. from the University of Michigan in 1925 with Phi Beta Kappa honors. He graduated from Harvard Medical School in 1929 at a time of quotas for outsiders. He fulfilled his internship and residency at Mt. Sinai Hospital in Cleveland. He came back to Boston in 1931 as a volunteer to join The Massachusetts General Hospital serving as the Chief of the Thyroid Unit from 1931 – 1943.

Two years after the discovery of artifically radioactivity, on November 12, 1936 Dr. Karl Compton, president of the Massachusetts Institute of Technology (MIT), spoke at Harvard Medical School.  President Compton’s topic was What Physics can do for Biology and Medicine. After the presentation Dr. Hertz spontaneously asked Dr. Compton this seminal question, “Could iodine be made radioactive artificially?” Dr. Compton responded in writing on December 15, 1936 that in fact “iodine can be made artificially radioactive.”

Shortly thereafter, a collaboration between Dr. Hertz (MGH) and Dr. Arthur Roberts, a physicist of MIT, was established. In late 1937, Hertz and Roberts created and produced animal studies  involving 48 rabbits that demonstrated that the normal thyroid gland concentrated Iodine 128 (non cyclotron produced), and the hyperplastic thyroid gland took up even more Iodine.  This was a GIANT step for Nuclear Medicine.

In early 1941, Dr. Hertz administer the first therapeutic treatment of MIT Markle Cyclotron produced radioactive iodine (RAI) at the Massachusetts General Hospital.  This  led to the first series of twenty-nine patients with hyperthyroidism being treated successfully with RAI. ( see “Research” RADIOACTIVE IODINE IN THE STUDY OF THYROID PHYSIOLOGY VII The use of Radioactive Iodine Therapy in Hyperthyroidism, Saul Hertz and Arthur Roberts, JAMA Vol. 31 Number 2).

In 1937, at the time of the rabbit studies Dr Hertz conceived of RAI in therapeutic treatment of thyroid carsonoma.  In 1942 Dr Hertz gave clinical trials of RAI to patients with thyroid carcinoma.

After serving in the Navy during World War II, Dr. Hertz wrote to the director of the Mass General Hospital in Boston, Dr. Paxon on March 12, 1946, “it is a coincidence that my new research project is in Cancer of the Thyroid, which I believe holds the key to the larger problem of cancer in general.”

Dr. Hertz established the Radioactive Isotope Research Institute, in September, 1946 with a major focus on the use of fission products for the treatment of thyroid cancer, goiter, and other malignant tumors. Dr Samuel Seidlin was the Associate Director and managed the New York City facilities. Hertz also researched the influence of hormones on cancer.

Dr. Hertz’s use of radioactive iodine as a tracer in the diagnostic process, as a treatment for Graves’ disease and in the treatment of cancer of the thyroid remain preferred practices. Saul Hertz is the Father of Theranostics.

Saul Hertz passed at 45 years old from a sudden death heart attack as documented by an autopsy. He leaves an enduring legacy impacting countless generations of patients, numerous institutions worldwide and setting the cornerstone for the field of Nuclear Medicine. A cancer survivor emailed, The cure delivered on the wings of prayer was Dr Saul Hertz’s discovery, the miracle of radioactive iodine. Few can equal such a powerful and precious gift. 

To read and hear more about Dr. Hertz and the early history of RAI in diagnosing and treating thyroid diseases and theranostics see –

http://saulhertzmd.com/home

 

   References in https://www.wjnm.org/article.asp?issn=1450-1147;year=2019;volume=18;issue=1;spage=8;epage=12;aulast=Hertz

 

Top

 

1.
Hertz S, Roberts A. Radioactive iodine in the study of thyroid physiology. VII The use of radioactive iodine therapy in hyperthyroidism. J Am Med Assoc 1946;131:81-6.  Back to cited text no. 1
2.
Hertz S. A plan for analysis of the biologic factors involved in experimental carcinogenesis of the thyroid by means of radioactive isotopes. Bull New Engl Med Cent 1946;8:220-4.  Back to cited text no. 2
3.
Thrall J. The Story of Saul Hertz, Radioiodine and the Origins of Nuclear Medicine. Available from: http://www.youtube.com/watch?v=34Qhm8CeMuc. [Last accessed on 2018 Dec 01].  Back to cited text no. 3
4.
Braverman L. 131 Iodine Therapy: A Brief History. Available from: http://www.am2016.aace.com/presentations/friday/F12/hertz_braverman.pdf. [Last accessed on 2018 Dec 01].  Back to cited text no. 4
5.
Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): A single-centre, single-arm, phase 2 study. Lancet Oncol 2018;19:825-33.  Back to cited text no. 5
6.
Krolicki L, Morgenstern A, Kunikowska J, Koiziar H, Krolicki B, Jackaniski M, et al. Glioma Tumors Grade II/III-Local Alpha Emitters Targeted Therapy with 213 Bi-DOTA-Substance P, Endocrine Abstracts. Vol. 57. Society of Nuclear Medicine and Molecular Imaging; 2016. p. 632.  Back to cited text no. 6
7.
Baum RP, Kulkarni HP. Duo PRRT of neuroendocrine tumours using concurrent and sequential administration of Y-90- and Lu-177-labeled somatostatin analogues. In: Hubalewska-Dydejczyk A, Signore A, de Jong M, Dierckx RA, Buscombe J, Van de Wiel CJ, editors. Somatostatin Analogues from Research to Clinical Practice. New York: Wiley; 2015.  Back to cited text no. 7

 

SOURCE

From: htziev@aol.com” <htziev@aol.com>

Reply-To: htziev@aol.com” <htziev@aol.com>

Date: Tuesday, March 2, 2021 at 11:04 AM

To: “Aviva Lev-Ari, PhD, RN” <AvivaLev-Ari@alum.berkeley.edu>

Subject: Dr Saul Hertz : Discovery for the Medical Uses of RADIOIODINE (RAI) MARCH 31ST: 80 Years

 

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2.0 LPBI is a Very Unique Organization

Author: Aviva Lev-Ari, PhD, RN

 

Leaders in Pharmaceutical Business Intelligence aka LPBI is a Registered Domain Name on WordPress.com.

  • LPBI is a Cloud-based Internet Business.

LPBI s not a manufacturing plant or a brick and mortar chain with Assets and Liabilities and AMORTIZATION and the discount rate that is chosen for the present value calculation (NPV) – these are terms not used for Intellectual Property portfolios and not used for MEDIA ventures.

Our Content is updated daily, it growth daily. We enjoy +20,000 e-Readers a month and the planned Medical Text Analysis with machine learning (Natural Language Processing) will general ~10 new digital artifacts per each existing article [N = +6,000].

Mission

  • Addressing Information Market needs for Text Analysis with NLP in Medicine, Life Sciences and Health Care
  • Development and application of a Content monetization system of the cutting edge Blockchain IT platform of a Transactions Network customized to implement NLP an several API layers of the Blockchain architecture as featured in https://pharmaceuticalintelligence.com/blockchain-transactions-network/

Venture Type

  • LPBI is an Internet-based Media e-Scientific Publisher and Medical Text Analysis with Machine Learning and Content Monetization of existing digital products and of to be produced digital products by Natural Language Processing (NLP)
  • NLP and Blockchain are cutting edge technologies [full flag implementation Blockchain is 5 years old!!].
  • When these two are combined together as LPBI 2.0 strategy states – a technological frontier for content monetization is born and could be applied to any content, not only pharmaceutical & medical, the LPBI pioneering case.
  • NOVELTY in methodologies, practice and digital artifacts in 3.3 GIGA BYTES.

2012-2020 – Milestones accomplished by 1.0 LPBI

  1. Multi-authoring system not in use by any other website on WordPress.com – World LARGEST hosting company of independent websites. It was Dr. Lev-Ari’s idea to augment the functionality and usage of the infrastructure from single to a multi-author system.
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  5. IP asset class X: Luminary Podcasts with Life Sciences Scholars
  6. IP asset class II: BioMed e-Series of 18 Volumes in Medicine and Life Sciences featuring +50,000 pages of thematic selections and expert interpretations FRONTIERS of the scientific inquiry in five specialties in Medicine and in several disciplines in the Life Sciences, Pharmaceutics and Health Care. LPBI’s e-Books pioneered the entrance in e-Scientific Publishing. In 6/2013 when we published the 1st book, Elsevier and John Wiley – DID NOT YET HAVE ANY e-BOOKS. Page downloads from books is 135,000. All Books on Amazon.com https://lnkd.in/ekWGNqA
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  10. IP asset class VIII: 2,500 subscribers to the website
  11. IP asset class VI: The Team of Experts in the Organization Chart, below 

LPBI’s corporate structure is presented in the Organization Chart, below

Dr. Lev-Ari is the Founder of 1.0 LPBI, 2012-2020 and 2.0 LPBI, 2021-2025

Aviva Lev-Ari, PhD, RN is the

  • Inventor of the curation methodology for clinical interpretation of scientific findings
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  • Inventor of One click e-Proceedings generation and the Tweeting template system
  • Inventor of the fusion of NLP and Blockchain
  • Of 6,068, under her name are 3,516 articles [Dashboard read on 3/1/2021]

Twelve Economic Segments for LPBI Group’s IP – Prospects for Transfer of Ownership

https://pharmaceuticalintelligence.com/2019-vista/opportunities-map-in-the-acquisition-arena/

  1.     Holding Companies, Investment Bankers and Private Equity
  2.     Information Technology Companies – Health Care
  3.     Scientific Publishers
  4.     Big Pharma
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  6.     Online Education
  7.     Health Insurance Companies & HMOs
  8.     Medical and Pharma Associations
  9.     Medical Education
  10.     Information Syndicators
  11.     Global Biotech & Pharmaceutical Conference Organizer
  12.     CRO & CRA

LPBI is Open Access and Equity Sharing

  • The Open Access status will change when we will migrate all the four classes of content relevant for Text Analysis with NLP to the Blockchain Transactions Network, IT platform is currently under design.
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Financial Projections are in an Excel file with three spreadsheets:

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Potential opportunities for ownership transfer needs to consider the Portfolio of TEN IP Asset Classes, SIX strategies for 2021-2025 and the TEAM

Inclusive Plan

  • A Portfolio of IP, 1.0 LPBI 
  • The 2.0 LPBI Vision [NLP Proof-of-Concept to be followed by scaling up to all content of four IP asset classes & Blockchain Transactions Network for B2B & B2C. Status: design phase and
  • The Team of Experts

Under development

  • IP Valuation Model per IP asset class is needed to be compared with Master_Financials
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Huffington Post sold to AOL for $319MM while ZERO revenues on the books and NO INVOLVEMENT of IB/VC/PE. AOL CEO was the decision maker.

Go Direct – find an interested CEO


FDA emergency use authorization would bring the public a third vaccine for the novel coronavirus – J&J single vaccine – Authorized on 2/28/2021

 

Reporter: Aviva Lev-Ari, PhD, RN

 

J&J’s Covid-19 vaccine gets vote of confidence from FDA advisory panel

The committee voted 22-0 on the question of whether the benefits of Johnson & Johnson’s Covid-19 vaccine outweigh its risks. FDA emergency use authorization would bring the public a third vaccine for the novel coronavirus.

The U.S. is one step closer to making available another Covid-19 vaccine after a panel of experts voted unanimously Friday to recommend emergency use authorization for a shot developed by Johnson & Johnson.

The independent panel, comprised of mostly physicians, voted 22-0 to support the vaccine with no one abstaining. These votes aren’t binding on the FDA, but the agency often follows the recommendations of its panels. A decision could come as early as this weekend. The two Covid vaccines currently cleared for emergency use received their authorizations the day after their respective advisory panel meetings.

Top ArticlesFDA authorizes third Covid-19 vaccine; J&J pledges 20M shots by month’s end

The Johnson & Johnson vaccine would offer an alternative to the ones currently available from the Pfizer and BioNtech alliance, and Moderna. Those messenger RNA vaccines must be distributed and stored at ultra-cold temperatures, then thawed before use. Those shots are given as two doses, weeks apart. The J&J vaccine can be kept at refrigerator temperatures. Another key difference is that the J&J jab requires a single shot. Together, those features will make the J&J vaccine easier to distribute to more people in more places through distribution channels that are already in place.

Panel members expressed support for the J&J vaccine, saying that the safety and efficacy data supported its authorization. But panelists also cautioned the public against picking vaccine favorites.

“It’s important that people do not think one vaccine is better than another,” said Cody Meissner, an infectious disease expert and professor of pediatrics at the Tufts University School of Medicine. “There is no preference for one vaccine over another and all vaccines work with what appears to be equal safety and equal efficacy as of this time.”

 

GUIDANCE DOCUMENT

Emergency Use Authorization for Vaccines to Prevent COVID-19 Guidance for Industry FEBRUARY 2021

Final
Docket Number:
FDA-2020-D-1137
Issued by:
Center for Biologics Evaluation and Research

FDA plays a critical role in protecting the United States (U.S.) from threats such as emerging infectious diseases, including the Coronavirus Disease 2019 (COVID-19) pandemic.  FDA is committed to providing timely guidance to support response efforts to this pandemic.

FDA is issuing this guidance to provide sponsors of requests for Emergency Use Authorization (EUA) for COVID-19 vaccines with recommendations regarding the data and information needed to support the issuance of an EUA under section 564 of the FD&C Act (21 U.S.C. 360bbb-3) for an investigational vaccine to prevent COVID-19 for the duration of the COVID-19 public health emergency.

SOURCE

 

FDA Statement on Vaccines and Related Biological Products Advisory Committee Meeting

The following is attributed to Acting Commissioner Janet Woodcock, M.D. and Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research


NEWS PROVIDED BY

U.S. Food and Drug Administration 

Feb 26, 2021, 18:50 ET


SILVER SPRING, Md.Feb. 26, 2021 /PRNewswire/ — Following today’s positive advisory committee meeting outcome regarding the Janssen Biotech Inc. COVID-19 Vaccine, the U.S. Food and Drug Administration has informed the sponsor that it will rapidly work toward finalization and issuance of an emergency use authorization. The agency has also notified our federal partners involved in vaccine allocation and distribution so they can execute their plans for timely vaccine distribution.

Additional Resources:

Media Contact: FDA Office of Media Affairs, 301-796-4540
Consumer InquiriesEmail or 888-INFO-FDA

SOURCE


Medical Device Representatives coach Surgeons in the Operating Rooms

Reporter: Aviva Lev-Ari, PhD, RN
Medical Device Representatives: The Untold Story

What Reps Don’t Do

As a surgeon and a healthcare executive, I’ve learned that the best device representatives are defined by what they won’t do: push a physician to use their product when it’s inappropriate. Villa says she sometimes sees patients who have blood clots in their arteries. “I will never recommend our product when there’s a clot because you can do more harm than good,” she says. “Ultimately, it’s up to the doctor’s discretion, but I’ll come right out and tell them, ‘I don’t know if CSI is the right product for that.’”

Just like physicians, device sales representatives have reputations to protect. A physician will recommend a helpful and knowledgeable sales representative to a colleague; but if the sales representative is clearly only interested in their bottom line — as opposed to the patient’s well-being — they’ll soon find that their calls go unanswered. For this reason, Nasser says he often finds himself advising physicians that his product isn’t appropriate for a patient. “You might not get the case,” he says, “but you’ll earn the trust of the physician.”

There’s a second — and more important — explanation for why these device representatives won’t push their products to boost sales. Simply put, that’s not why they’re in business. Nasser, for example, got into device sales after his father died of a heart attack. “I approach every case as if that were my family member and I ask what would be best for them,” he says.

“You can’t fake the passion and the caring you have,” adds Staub. “People see through if it’s just a business transaction.” Instead, he attributes his longevity to “engaging physicians in an educational way and getting across that you can be a partner in the care of their patients.”

When asked why she does her job, Villa thinks about the 77-year old woman she helped the day she drove to the hospital early in the morning. When the woman’s foot, which initially had turned grey, started to turn pink after the procedure, Villa says she was overcome with “a wonderful feeling. That patient had a fear of losing her limb and woke up knowing that her leg was still there. Saving limbs and saving lives. That’s the beauty of our job.”

¹ O’Connor B, Pollner F, Fugh-Berman A (2016) Salespeople in the Surgical Suite: Relationships between Surgeons and Medical Device Representatives. PLoS ONE 11(8): e0158510. https://doi.org/10.1371/journal.pone.0158510

² White, T. Stanford Medicine Magazine, 2006, Fall Issue. Father of invention – Stanford Medicine Magazine – Stanford University School of Medicine

³ Gawande, A. The New Yorker, October 3, 2011. The Coach in the Operating Room | The New Yorker

 

SOURCE

 

https://www.cardiovascularbusiness.com/sponsored/2052/medical-device-representatives-untold-story

From: Cardiovascular Business <announcements@mail.cardiovascularbusiness.com>

Reply-To: Cardiovascular Business <announcements@mail.cardiovascularbusiness.com>

Date: Monday, March 1, 2021 at 10:30 AM

To: “Aviva Lev-Ari, PhD, RN” <AvivaLev-Ari@alum.berkeley.edu>

Subject: The Untold Story of Medical Device Reps: A Physician’s Perspective


2021 Virtual World Medical Innovation Forum, Mass General Brigham, Gene and Cell Therapy, VIRTUAL May 19–21, 2021

 

The 2021 Virtual World Medical Innovation Forum will focus on the growing impact of gene and cell therapy.
Senior healthcare leaders from all over look to shape and debate the area of gene and cell therapy. Our shared belief: no matter the magnitude of change, responsible healthcare is centered on a shared commitment to collaborative innovation–industry, academia, and practitioners working together to improve patients’ lives.

https://worldmedicalinnovation.org/agenda/

Virtual | May 19–21, 2021

 

 

Leaders in Pharmaceutical Business Intelligence (LPBI) Group

will cover the event in Real Time

 

Aviva Lev-Ari, PhD, RN

Founder LPBI 1.0 & LPBI 2.0

will be in attendance producing the e-Proceedings

and the Tweet Collection of this Global event expecting +15,000 attendees

 

 

LPBI’s Eighteen Books in Medicine

https://lnkd.in/ekWGNqA

Among them, books on Gene and Cell Therapy include the following:

 

 

Topics

The 2021 Forum will be held virtually and focus on gene and cell therapy.

AAV | Ophthalmology, Otology and Neurology

Gene Therapy | Oncolytic Viruses

CAR- T | Cellular Therapies

Stem Cells | Neurodegenerative Diseases, Regenerative Medicine

GCT | Infectious Disease, Hematology and Diabetes

Gene Editing | RNA Technologies

GCT Manufacturing | Supply Chain

Equity and Access | Emerging GCT Environment

GCT Investor Priorities

Putting GCT to Work | Payers, Providers | Regulatory

*Our agenda is currently under formation and is subject to change. Please continue checking for a more up to date agenda.


Inhibitory CD161 receptor recognized as a potential immunotherapy target in glioma-infiltrating T cells by single-cell analysis

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

 

Brain tumors, especially the diffused Gliomas are of the most devastating forms of cancer and have so-far been resistant to immunotherapy. It is comprehended that T cells can penetrate the glioma cells, but it still remains unknown why infiltrating cells miscarry to mount a resistant reaction or stop the tumor development.

Gliomas are brain tumors that begin from neuroglial begetter cells. The conventional therapeutic methods including, surgery, chemotherapy, and radiotherapy, have accomplished restricted changes inside glioma patients. Immunotherapy, a compliance in cancer treatment, has introduced a promising strategy with the capacity to penetrate the blood-brain barrier. This has been recognized since the spearheading revelation of lymphatics within the central nervous system. Glioma is not generally carcinogenic. As observed in a number of cases, the tumor cells viably reproduce and assault the adjoining tissues, by and large, gliomas are malignant in nature and tend to metastasize. There are four grades in glioma, and each grade has distinctive cell features and different treatment strategies. Glioblastoma is a grade IV glioma, which is the crucial aggravated form. This infers that all glioblastomas are gliomas, however, not all gliomas are glioblastomas.

Decades of investigations on infiltrating gliomas still take off vital questions with respect to the etiology, cellular lineage, and function of various cell types inside glial malignancies. In spite of the available treatment options such as surgical resection, radiotherapy, and chemotherapy, the average survival rate for high-grade glioma patients remains 1–3 years (1).

A recent in vitro study performed by the researchers of Dana-Farber Cancer Institute, Massachusetts General Hospital, and the Broad Institute of MIT and Harvard, USA, has recognized that CD161 is identified as a potential new target for immunotherapy of malignant brain tumors. The scientific team depicted their work in the Cell Journal, in a paper entitled, “Inhibitory CD161 receptor recognized in glioma-infiltrating T cells by single-cell analysis.” on 15th February 2021.

To further expand their research and findings, Dr. Kai Wucherpfennig, MD, PhD, Chief of the Center for Cancer Immunotherapy, at Dana-Farber stated that their research is additionally important in a number of other major human cancer types such as 

  • melanoma,
  • lung,
  • colon, and
  • liver cancer.

Dr. Wucherpfennig has praised the other authors of the report Mario Suva, MD, PhD, of Massachusetts Common Clinic; Aviv Regev, PhD, of the Klarman Cell Observatory at Broad Institute of MIT and Harvard, and David Reardon, MD, clinical executive of the Center for Neuro-Oncology at Dana-Farber.

Hence, this new study elaborates the effectiveness of the potential effectors of anti-tumor immunity in subsets of T cells that co-express cytotoxic programs and several natural killer (NK) cell genes.

The Study-

IMAGE SOURCE: Experimental Strategy (Mathewson et al., 2021)

 

The group utilized single-cell RNA sequencing (RNA-seq) to mull over gene expression and the clonal picture of tumor-infiltrating T cells. It involved the participation of 31 patients suffering from diffused gliomas and glioblastoma. Their work illustrated that the ligand molecule CLEC2D activates CD161, which is an immune cell surface receptor that restrains the development of cancer combating activity of immune T cells and tumor cells in the brain. The study reveals that the activation of CD161 weakens the T cell response against tumor cells.

Based on the study, the facts suggest that the analysis of clonally expanded tumor-infiltrating T cells further identifies the NK gene KLRB1 that codes for CD161 as a candidate inhibitory receptor. This was followed by the use of 

  • CRISPR/Cas9 gene-editing technology to inactivate the KLRB1 gene in T cells and showed that CD161 inhibits the tumor cell-killing function of T cells. Accordingly,
  • genetic inactivation of KLRB1 or
  • antibody-mediated CD161 blockade

enhances T cell-mediated killing of glioma cells in vitro and their anti-tumor function in vivo. KLRB1 and its associated transcriptional program are also expressed by substantial T cell populations in other forms of human cancers. The work provides an atlas of T cells in gliomas and highlights CD161 and other NK cell receptors as immune checkpoint targets.

Further, it has been identified that many cancer patients are being treated with immunotherapy drugs that disable their “immune checkpoints” and their molecular brakes are exploited by the cancer cells to suppress the body’s defensive response induced by T cells against tumors. Disabling these checkpoints lead the immune system to attack the cancer cells. One of the most frequently targeted checkpoints is PD-1. However, recent trials of drugs that target PD-1 in glioblastomas have failed to benefit the patients.

In the current study, the researchers found that fewer T cells from gliomas contained PD-1 than CD161. As a result, they said, “CD161 may represent an attractive target, as it is a cell surface molecule expressed by both CD8 and CD4 T cell subsets [the two types of T cells engaged in response against tumor cells] and a larger fraction of T cells express CD161 than the PD-1 protein.”

However, potential side effects of antibody-mediated blockade of the CLEC2D-CD161 pathway remain unknown and will need to be examined in a non-human primate model. The group hopes to use this finding in their future work by

utilizing their outline by expression of KLRB1 gene in tumor-infiltrating T cells in diffuse gliomas to make a remarkable contribution in therapeutics related to immunosuppression in brain tumors along with four other common human cancers ( Viz. melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma, and colorectal cancer) and how this may be manipulated for prevalent survival of the patients.

References

(1) Anders I. Persson, QiWen Fan, Joanna J. Phillips, William A. Weiss, 39 – Glioma, Editor(s): Sid Gilman, Neurobiology of Disease, Academic Press, 2007, Pages 433-444, ISBN 9780120885923, https://doi.org/10.1016/B978-012088592-3/50041-4.

Main Source

Mathewson ND, Ashenberg O, Tirosh I, Gritsch S, Perez EM, Marx S, et al. 2021. Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis. Cell.https://www.cell.com/cell/fulltext/S0092-8674(21)00065-9?elqTrackId=c3dd8ff1d51f4aea87edd0153b4f2dc7

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First single-course ‘curative’ CRISPR Shot by Intellia rivals Alnylam, Ionis and Pfizer

Reporter: Aviva Lev-Ari, PhD, RN

 

Intellia to kick-start first single-course ‘curative’ CRISPR shot, as it hopes to beat rivals Alnylam, Ionis and Pfizer

It’s been a good year for Intellia: One of its founders, Jennifer Doudna, Ph.D., nabbed the Nobel Prize in Chemistry for her CRISPR research.

Now, the biotech she helped build is putting that to work, saying it now plans the world’s first clinical trial for a single-course therapy that “potentially halts and reverses” a condition known as hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN).

This genetic disorder occurs when a person is born with a specific DNA mutation in the TTR gene, which causes the liver to produce a protein called transthyretin (TTR) in a misfolded form and build up in the body.

hATTR can manifest as polyneuropathy (hATTR-PN), which can lead to nerve damage, or cardiomyopathy (hATTR-CM), which involves heart muscle disease that can lead to heart failure.

This disorder has seen a lot of interest in recent years, with an RNAi approach from Alnylam seeing an approval for Onpattro a few years back, specifically for hATTR in adults with damage to peripheral nerves.

Ionis Pharmaceuticals and its rival RNAi drug Tegsedi also saw an approval in 2018 for a similar indication.

They both battle with Pfizer’s older med tafamidis, which has been approved in Europe for years in polyneuropathy, and the fight could spread to the U.S. soon.

The drug, now marketed as Vyndaqel and Vyndamax, snatched up an FDA nod last May to treat both hereditary and wild-type ATTR patients with a heart condition called cardiomyopathy.

While coming into an increasingly crowed R&D area, Intellia is looking for a next-gen approach, and has been given the go-ahead by regulators ion the U.K, to start a phase 1 this year.

The idea is for Intellia’s candidate NTLA-2001, which is also partnered with Regeneron, to go beyond its rivals and be the first curative treatment for ATTR.

By applying the company’s in vivo liver knockout technology, NTLA-2001 allows for the possibility of lifelong transthyretin (TTR) protein reduction after a single course of treatment. If this works, this could in essence cure patients of the their disease.

The 38-patient is set to start by year’s end.

“Starting our global NTLA-2001 Phase 1 trial for ATTR patients is a major milestone in Intellia’s mission to develop medicines to cure severe and life-threatening diseases,” said Intellia’s president and chief John Leonard, M.D.

“Our trial is the first step toward demonstrating that our therapeutic approach could have a permanent effect, potentially halting and reversing all forms of ATTR. Once we have established safety and the optimal dose, our goal is to expand this study and rapidly move to pivotal studies, in which we aim to enroll both polyneuropathy and cardiomyopathy patients.”

SOURCE

https://www.fiercebiotech.com/biotech/intellia-to-kickstart-first-single-course-curative-crispr-shot-as-it-hopes-to-beat-rivals

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Contribution of Nervous System Functional Deterioration to late-life Mortality: The Role Neurofilament light chain (NfL) a Blood Biomarker for the Progression of Neurological Diseases and its Correlation to Age and Life Expectancy

 

Reporter: Aviva Lev-Ati, PhD, RN

 

A neuronal blood marker is associated with mortality in old age

Abstract

Neurofilament light chain (NfL) has emerged as a promising blood biomarker for the progression of various neurological diseases. NfL is a structural protein of nerve cells, and elevated NfL levels in blood are thought to mirror damage to the nervous system. We find that plasma NfL levels increase in humans with age (n = 122; 21–107 years of age) and correlate with changes in other plasma proteins linked to neural pathways. In centenarians (n = 135), plasma NfL levels are associated with mortality equally or better than previously described multi-item scales of cognitive or physical functioning, and this observation was replicated in an independent cohort of nonagenarians (n = 180). Plasma NfL levels also increase in aging mice (n = 114; 2–30 months of age), and dietary restriction, a paradigm that extends lifespan in mice, attenuates the age-related increase in plasma NfL levels. These observations suggest a contribution of nervous system functional deterioration to late-life mortality.

SOURCE

How long will a healthy older person live? A substance in blood may provide a clue

Levels of a substance in nonagenerians’ and centenarians’ blood accurately predict how much longer they’re going to live. The substance comes from the brain.

The findings, in a study published in Nature Aging, could prove useful in developing life-extending drugs. They also raise questions about the brain’s role in aging and longevity.

The study, conducted by Stanford investigators including neuroscientist Tony Wyss-Coray, PhD, in collaboration with researchers in Denmark and Germany, zeroed in on a substance whose technical name is neurofilament light chain (abbreviated NfL). A structural protein produced in the brain, NfL is found in trace amounts in cerebrospinal fluids and blood, where it’s an indicator of damage to long extensions of nerve cells called axons.

Axons convey signals from one nerve cell to the next and are critical to all brain function. You’d rather they remain intact.

Too much NfL (different from the NFL)

High NfL levels in the blood have previously been associated with Alzheimer’s disease, multiple sclerosis, Huntington’s disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease) and other neurological disorders. But the people monitored in the new study were generally pretty healthy for their age.

The researchers first looked at 122 people whose ages ranged from 21 to 107, and found increasing blood levels of NfL — as well as increasing variation among individuals — with increasing age.

Next, the scientists followed the fates of 135 people age 100 or over for a four-year period. Most of those centenarians were in good shape to begin with, as shown by their performance on standard tests of mental ability and by a measure of their capacity to meet the routine demands of daily living.

Not unexpectedly, those whose mental tests indicated impairment had more NfL in their blood than those with the sharpest minds did. And those with low levels were substantially likelier to live longer than those with high levels.

A look at people in their 90s confirmed the findings in the over-100 group. Blood NfL levels among 180 93-year-olds not only predicted the duration of these folks’ survival, but did so better than mental or daily-coping test scores did.

The investigators showed that mice’s blood NfL levels, too, increase with age. But cutting their caloric intake, beginning in young adulthood — already known to prolong the lives of mice and numerous other species — chopped the little creatures’ blood levels of this substance in half in old age. (This new finding doesn’t prove that lowering NfL blood levels causes increased longevity, but it’s consistent with it.)

Tie to life expectancy?

At a minimum, NfL appears to accurately flag mortality’s approach. That means it might be possible to monitor it as a surrogate marker for remaining life expectancy, much as blood cholesterol levels are used as proxies for cardiovascular health. If so, it could someday help drug developers assess life-extending interventions’ efficacy.

Clinical trials of interventions believed to enhance longevity have been impractical, because it would almost certainly take so long to get a statistically significant result that such trials would be hugely expensive — a major hang-up for pharmas considering investment in longevity drugs. But monitoring a proxy such as NfL could cut years off of such trials’ duration, perhaps encouraging drug developers to dive into the clinical arena with life-prolonging pharmacological candidates.

Possibly most intriguing of all: The new findings hint that maintaining a healthy brain in old age is the best route to a long life.

“It will be interesting to see how and why the brain might be so important in counting down our final years and months,” Wyss-Coray told me.

Photo by Pablo Bendandi


COVID-19-vaccine rollout risks and challenges

Reporter : Irina Robu, PhD

BioNTech and Pfizer and Moderna COVID-19 vaccines received Emergency Use Authorization in January 2021 in Canada, European Union, United Kingdom and United States. However, in certain places COVID-19 has hit a few hindrances such as stockpiles have accumulated, deployment to vulnerable countries and at-risk groups has been slower than expected.  Yet, experts can see the light at the end of the tunnel of the pandemic. In United States, hundred of organization take a vital role in vaccine deployment, adapting their operations to meet the demands for volume, speed and better technology. Tens of thousands of transporters, vaccine handlers, medical and pharmacy staff, and frontline workers have mandatory training on the specific characteristics of each manufacturer’s distinct vaccines.

The common operating model provides the details of end-to-end vaccine deployment. Possible areas of risk to the rapid delivery of COVID-19 vaccines in the United States include:

Raw-materials constraints in production scaling

Scaling access to material and boosting production levels can cause logistical, contractual and even diplomatic challenges, requiring new forms of collaboration. The top two US manufacturers, for example, can produce 280 million vials per year, capable of holding up to 2.8 billion doses.

Quality-assurance challenges in manufacturing

Generating yields to produce a new class of vaccines—such as those based on mRNA or viral vectors—at an unprecedented scale (1.8 billion to 2.3 billion doses by mid-2021), manufacturers have required massive volumes of inputs, a larger technical workforce.

Cold-chain logistics and storage-management challenges

Manufacturers and distributors are preparing to maintain cold-chain requirements for distribution and long-term storage of mRNA-based vaccines. Large amounts of dry ice may be needed at various locations before administration.

Increased labor requirements

Complex protocols for handling and preparing COVID-19 vaccines have the potential to strain labor capacities or divert workers from other critical roles.

Wastage at points of care

Errors in storing, preparing, or scheduling administration of doses at points of care will have significant consequences and proper on-site storage conditions are also of critical importance.

IT challenges

IT systems, including vaccine-tracking systems and immunization information systems will be vital for allocating, distributing, recording, and monitoring the deployment of vaccines.

There are several possible approaches to help mitigate each of the six risks discussed, each with practical steps for organization to take across the common operating model.

Building resilient raw-materials supplies

  • Resilience planning.Producers can partner with global suppliers of raw materials and ancillary-product manufacturers to create redundancies.
  • Collaboration between industry and government.Ongoing industry engagement with government is essential for ramping-up production and maintaining high levels of production.

 Scaling manufacturing within quality guidelines

  • Scale manufacturing in new and existing facilities.  Various digital and analytics tools can help expand capacity and scale more quickly.
  • Assure quality and yield in current facilities. By continuing to coordinate with regulators, manufacturers and authorities can certify that procedures and dosage quality meet both long-established and newly issued guidelines.
  • Establish predictable supplier plans. Each manufacturing stakeholder can follow a clearly defined plan and they can also conduct regular cross-functional risk reviews to ensure that quality.

Optimizing the cold chain

  • Build redundancy into distribution.Manufacturers, distributers should quickly identify points of failure and creating redundancies at each stage.
  • Leverage feedback loops.Reporting systems could be set up to capture supply-chain disruption events as soon as they happen, with data used to refine best practices and procedures and avoid further losses.
  • Use point-of-care stock management.Vaccine inventories can be redistributed to locations with greater demand. Strategies to avoid over stockpiling must confirm maintenance of the cold chain to prevent risks to the receiving administration site.

Addressing labor shortages

  • Use several types of point-of-care facilities.Rely on hospitals and primary-care locations for vaccine administration, in addition to retail pharmacies.
  • Streamline administration across sites.Deploying vaccines at larger, streamlined vaccination sites can be more efficient and improve patient safety, labor utilization, and speed of vaccination.

 Reducing spoilage at points of care

  • Track and monitor spoilage at points of care.Manufacturers and distributors can collaborate to establish the means to identify and trace instances of spoilage. They can learn from experience and refine guidance, training, certification, and allocation to optimize utilization of doses.
  • Pace first-dose allocation.Allocation of first doses to populations and locations where the need is greatest and the confidence in the availability of second doses is high (such as healthcare professionals and vulnerable populations in nursing homes).
  • Prioritize second doses.Authorities can help ensure that the recommended two-dose course schedule for such vaccines as the Pfizer-BioNTech, Moderna, and AstraZeneca vaccines are duly completed.
  • Establish recipient commitment.Vaccine recipients could be asked to commit to second-dose appointments at their point of care before first-dose administration.
  • Manage certification.National and local government institutions can collaborate to ensure that vaccination certifications are withheld until recipients receive their second dose.

Meeting IT challenges

  • Balance IT upgrades and resilience.Stakeholders should identify IT systems that can be relied upon in the deployment of COVID-19 vaccines and assess their ability to perform at scale.
  • Share cyberthreat intelligence.COVID-19-vaccine stakeholders should agree upon common requirements and processes for generating and sharing threat intelligence.
  • Establish means of demonstrating immunity.Manufacturers and distributers can commission systems to track and verify that vaccine recipients have demonstrated immunity. if it will release them from travel limits and other pandemic-related restrictions.

Although not one organization is involved for managing vaccine deployment, but the risks can be fully address if organizations align on lead organization to build scenarios to test responses to emerging crises. The groups could align on lead organizations to manage issues while building scenarios to test responses to emerging crises. The benefits in managing each of these risks could be demonstrated with compelling metrics and communications.  As COVID-19-vaccine rollouts commence, the steps mentioned above can be undertaken by manufactures, distributors and governments.

SOURCE

https://www.mckinsey.com/business-functions/risk/our-insights/the-risks-and-challenges-of-the-global-covid-19-vaccine-rollout?cid=other-eml-nsl-mip-mck&hlkid=19a51f848bee4d00806d2da81315f70d&hctky=2071733&hdpid=062f1841-f911-48f3-ab14-a9f92e30721f#