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MedNess: bite-size biopharma and medtech news

27th January, 2021
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MedNess This Week
HIGHLIGHTS
Onco-I-Analyse
Merck KGaA and GSK’s bintrafusp alfa to be discontinued in lung cancer
On 20th January, Merck KGaA and GSK suffered a setback as the head-to-head Phase III INTR@PID Lung 037 trial of bintrafusp alfa, TGFβxPD-L1 bispecific antibody, against pembrolizumab as frontline treatment in high PD-L1 expressing advanced NSCLC will be discontinued.
Background: Checkpoint inhibitors (CHKPTis) have been the backbone treatment in non-oncogenic mutation driven locally advanced and metastatic NSCLC with pembrolizumab dominating the space. However, patients progressing on CHKPTis usually have limited treatment options, including rechallenge. Bispecific antibodies like bintrafusp alfa are being developed as a CHKPTi successor class of treatment options.
As part of the 2019 agreement, Merck was to receive €3.7 billion ($4.5 billion) from GSK as upfront payment (€300 million ($363 million)) and in potential milestones. Both companies were to jointly develop and commercialize bintrafusp alfa after it showed promising ORR in a Phase I study.
Details: The decision was made after the Independent Data Monitoring Committee (IDMC) reviewed the data from the clinical study and recommended to stop the trial on 19th January as the study is not likely to meet the co-primary endpoint, especially progression free survival. No additional safety concerns were observed in the trial.
Implications: Bintrafusp alfa is one of the leading assets for GSK and Merck KGaA and therefore, subdues their oncology ambitions. The failure comes as a surprise as last year in October the trial had passed the interim futility analysis. However, both companies plan to utilize the insights for future studies. Merck is determined to evaluate ‘multiple non-correlated parallel hypotheses’ for bintrafusp alfa across several tumors and patient segments as part of the INTR@PID Clinical Trial Program, including biliary tract cancer (2L - INTR@PID BTC 047 with data expected in Q1 21; 1L - INTR@PID BTC 055), cervical cancer (platinum-experienced - INTR@PID CERVICAL 017, INTR@PID CERVICAL 046), NSCLC (INTR@PID LUNG 005, INTR@PID LUNG 024), TNBC (INTR@PID BREAST 020), urothelial cancer (INTR@PID UROTHELIAL 152). Several big players are evaluating standalone TGF-β agents in various combinations, however for now, pembrolizumab continues to dictate the treatment choices for 1L, non-oncogenic mutation driven NSCLC.
Collated by : Shilpa Rawal, PhD
COVID Special
Johnson and Johnson announces publishing of the Phase 1/2a data for their COVID-19 vaccine candidate in the New England Journal of Medicine
Earlier this month, the interim results from the Phase 1/2a of Johnson and Johnson’s candidate COVID-19 vaccine was published in the New England Journal of Medicine. The company’s vaccine candidate, JNJ-78436735, is a single dose investigational candidate vaccine for COVID-19 that is currently being developed by the Janssen Pharmaceutical Companies of Johnson and Johnson. This Phase 1/2a of the study has been funded either in whole or in part with federal funds from BARDA. The company intends to announce topline Phase 3 data from this study in late January 2021. If the vaccine candidate meets the standards of safety and efficacy required for this single dose vaccine, the company intends to submit an emergency use authorization right afterwards to speed up the process of getting the vaccine out in the market.
Regeneron announces the agreement with the federal government that involves the purchase of additional COVID-19 antibody cocktail doses 
The Department of Defense (DoD) and the US Department of Health and Human Services (HHS) have entered into an agreement with Regeneron to purchase additional COVID-19 antibody cocktail doses for the use in non-hospitalized COVID-19 patients. This agreement is a part of the federal government’s operation Warp Speed goals. The antibodies in question are imdevimab and casirivimab. These doses will be free for patients, but healthcare facilities may charge fees related to administration. Following the acquirement of additional doses, the federal government shall continue to coordinate allocation of these doses to states and health departments. Based on a previous agreement, Regeneron is already supplying doses to treat 300,000 people.
"COVID-19 continues to sicken hundreds of thousands of Americans every day and the people of Regeneron are committed to help," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "Tackling the COVID-19 pandemic will require a combination of public health measures, vaccines and therapeutics. We are pleased to work with the U.S. government to supply our antibody cocktail as an important weapon in this fight."
Click here for more COVID news
Collated by : Esha Sehanobish, PhD
Drug Approvals
FDA Approves OPDIVO® (nivolumab) + CABOMETYX® (cabozantinib) Combination as First-line Treatment for Patients with Advanced RCC
“At Bristol Myers Squibb, we are focused on developing transformative medicines that may improve survival for people living with cancer. The role of OPDIVO + YERVOY is well established for intermediate/poor-risk patients with advanced RCC, and today’s achievement extends the potential of an OPDIVO-based combination to even more patients,” says Adam Lenkowsky, general manager and head, U.S., Oncology, Immunology, Cardiovascular, Bristol Myers Squibb.1 “OPDIVO in combination with CABOMETYX brings together the strong heritage of both medicines to now provide physicians a new combination in advanced RCC that may offer improved outcomes to patients for whom an immunotherapy plus tyrosine kinase inhibitor regimen is appropriate.”1
European Commission Approves BAVENCIO® (avelumab) for First-Line Maintenance Treatment of Locally Advanced or Metastatic Urothelial Carcinoma
“Avelumab is the only immunotherapy to demonstrate a significant improvement in overall survival in the first-line setting in a Phase III study in advanced or metastatic bladder cancer. With this approval by the European Commission, we can now offer patients a potential new first-line maintenance standard of care that may help them live longer,” said Professor Thomas Powles, MD, Director of Barts Cancer Centre, London, UK.
Click here for more Drug Approvals
Regulatory News
Acceptance and Priority Review of BLA for Retifanlimab as a Potential Treatment for Patients with Squamous Cell Carcinoma of the Anal Canal (SCAC) announced
“Patients with SCAC who have progressed after first-line chemotherapy treatment currently have no approved treatments available, and we are encouraged that the FDA’s acceptance of this BLA for Priority Review brings us one step closer to addressing this historically neglected, yet important, tumor,” said Lance Leopold, M.D., Group Vice President, Immuno-Oncology Clinical Development, Incyte. “Despite SCAC being a rare disease, its incidence is increasing and its impact is profound. We look forward to working with the FDA to potentially fill an unmet need and advance progress in SCAC for patients.”
FDA Accepts for Priority Review Application for Opdivo® (nivolumab) + Chemotherapy as 1L Treatment in Metastatic Gastric Cancer, Gastroesophageal Junction Cancer and Esophageal Adenocarcinoma
“The FDA’s acceptance of our application marks important progress toward our goal of advancing treatment options for patients with esophageal or gastroesophageal junction cancer, in this case in early-stage disease,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “We look forward to working with the FDA to potentially bring Opdivo to these patients, who face a critical unmet need and remain at high risk for disease recurrence.”
FDA Accepts for Priority Review Application for Opdivo® (nivolumab) as Adjuvant Therapy for Patients with Resected Esophageal or Gastroesophageal Junction Cancer
“The FDA’s acceptance of our application marks important progress toward our goal of advancing treatment options for patients with esophageal or gastroesophageal junction cancer, in this case in early-stage disease,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “We look forward to working with the FDA to potentially bring Opdivo to these patients, who face a critical unmet need and remain at high risk for disease recurrence.”
Trial Results
Calquence met primary efficacy endpoint vs ibrutinib in Ph 3 ELEVATE-RR trial in CLL patients
José Baselga, Executive Vice President, Oncology R&D, said: “With over forty months of follow-up, today’s results confirm that Calquence, a selective BTK inhibitor, displays superior safety in atrial fibrillation without compromising efficacy. The totality of the data confirm our confidence in the favourable benefit-risk profile of Calquence.”
Trial/Program Status
FDA Lifts Partial Clinical Hold on PRS-343 Ph 1 Studies
"It has been rewarding to see the impact of PRS-343 on the lives of patients in these studies. Data continue to be encouraging, and the clinical benefit linked to single-agent activity that we have seen attests to the potential of this therapy and, more broadly, our localized 4-1BB agonism approach," said Stephen S. Yoder, President and Chief Executive Officer of Pieris. "We are excited to advance this program into the proof-of-concept phase and look forward to sharing more details about the study later this quarter."
Ph 1b Clinical Trial of LB-100 to be initiated to Treat Small Cell Lung Cancer
John S. Kovach, M.D., Lixte founder and chief executive officer, said “Small cell lung cancer (SCLC) comprises approximately 15% of all lung cancers worldwide with about 30,000 new cases annually in the US. Although this very aggressive neuroendocrine tumor is much more sensitive to cytotoxic chemotherapy and radiation than the most common type of lung cancer, SCLC patients soon relapse after treatment and have a dismal prognosis. Recently, the addition of an immune blocker, atezolizumab, to carboplatin plus etoposide showed the first significant but modest improvement in median progression free survival from 4.3 to 5.2 months, and in median overall survival from 10.3 to 12.3 months.”
Click here for more Trial Statuses
Collated by : Richa Tewari, PhD
Medness Plus
FDA approves Cabenuva, the first extended-release regimen for the treatment of adults with HIV 
FDA recently approved cabotegravir and rilpivirine (Cabenuva) as the first extended-release injectable drug regimen for the treatment of adult individuals with the immunodeficiency virus type 1 (HIV-1) infection. It will be administered once a month. This treatment will be used for adults with HIV to replace a current antiretroviral regimen in those who are virologically suppressed on a stable antiretroviral regimen. It will also be used for treatment in those with no history of treatment failure or resistance to either of the constituents.
Lynn Baxter, Head of North America, ViiV Healthcare, said: “Today’s FDA approval of Cabenuva represents a shift in the way HIV is treated, offering people living with HIV a completely new approach to care. Cabenuva reduces the treatment dosing days from 365 days to 12 days per year. At ViiV Healthcare, we are dedicated to ensuring no one living with HIV is left behind and adding this first-of-its-kind regimen to our industry-leading portfolio of innovative medicines reinforces our mission.”
Abbvie announces positive results from two Phase 3 induction studies investigating the efficacy of Risankizumab in the treatment of Crohn’s disease 
Abbvie announces positive results from its two Phase 3 induction studies. ADVANCE and MOTIVATE are currently investigating the use of two doses of risankizumab (SKYRIZI®) for the treatment of patients with moderate to severe Crohn’s disease. The two doses under study are 600 and 1200 mg of Risankizumab. Risankizumab is a part of the collaboration between Abbvie and Boehringer Ingelheim, with the former leading development and commercialization, worldwide.
"The progressive nature of Crohn's disease makes it critical that treatment options go beyond symptoms to help patients achieve endoscopic response," said Michael Severino, M.D., vice chairman and president, AbbVie. "Despite the availability of current treatments, many patients still do not achieve disease control. These positive results show how targeting IL-23 can rapidly induce improvements for people living with this condition. We look forward to advancing research showing risankizumab's potential to improve clinical and endoscopic outcomes and minimize the burden of Crohn's disease for patients."
Click here for more MedNess Plus
Collated by : Esha Sehanobish, PhD
Medness Reviews

Researchers Identify a Circadian Clock Gene Linked to Prostrate Cancer Progression
Several studies have shown a link between disruption in circadian rhythm and increased incidence of some cancers. Now, researchers at Sidney Kimmel Cancer - Jefferson Health (SKCC) have identified a circadian clock gene that seems to play a major role in prostate cancer progression.
In the study, published in the journal Nature Communications, the researchers analyzed prostate tissue and found that a protein called CRY1 was elevated in late-stage prostate cancer. They also discovered CRY 1 was induced by the receptor for the male hormone androgen—a major culprit in the development and progression of prostate cancer.
CRY1 is well known for its role in regulating circadian rhythms. Abnormalities in the gene have been linked to sleep-related illnesses like delayed sleep phase disorder, but its role in cancer progression is not well understood.
The researchers then probed the possible role of CRY1 in DNA repair. Using the prostate cancer samples, as well as cultured cells and animal models, they induced DNA damage and then tracked levels of CRY1.
They found that CRY1 was elevated in response to DNA damage, suggesting the gene may shield prostate tumors from DNA-damaging treatments.
The team further aims to explore therapies that can target and block CRY1, including currently marketed cancer drugs. They also plan to study other genes that are involved in circadian rhythm to better understand the role these genes may play in cancer.

Servier and MiNA Therapeutics Partner to develop New Class of Drugs for Neurological Diseases
France based Servier has partnered with UK based MiNA Therapeutics for developing small activating RNA (saRNA) therapies to treat neurological diseases.
First described in 2006, small activating RNAs are short, double-stranded oligonucleotides, similar to siRNAs. They selectively increase gene transcription and studies have shown that in mammals, saRNAs can activate a wide variety of genes.
saRNAs are an entirely new class of drugs. The saRNA technology is MiNa’s focus is based on inventions from the Norwegian University of Science and Technology. The company has also in-licensed fundamental patents from UT Southwestern Medical Center that covers RNA activation therapeutics.
According to the deal, MiNA will leverage its saRNA platform to identify possible treatments to restore normal cell function in neurological diseases. Servier will handle preclinical and clinical development of potential candidates. Servier also will have the option for commercialization of any products coming out of the partnership.
The first target covered by the deal is worth up to €220 million ($267 million) to MiNA in upfront, development and commercial milestone payments. However, no specific neurological indications were disclosed.
MiNA currently has five compounds in its pipeline. Three are in the discovery stage for undisclosed metabolic, immuno-oncology and genetic targets. The other two programs are for the same drug, MTL-CEBPA, which are in Phase I/II trials, one with Bayer and Onyx Pharmaceuticals Nexavar (sorafenib) for hepatocellular carcinoma (HCC) and the other with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) for advanced solid tumors.
Servier is the latest pharma company to see potential in saRNA molecules. MiNA has previously landed deals with AstraZeneca and Boehringer Ingelheim on the strength of its saRNA technology.
Medness Business
Onco-News
Turnstone Biologics Acquires Myst Therapeutics to add proprietary tumor infiltrating lymphocyte (“TIL”) technology and programs to growing portfolio
“Myst has created an industry-best selection strategy for identifying, expanding and stimulating antigen-reactive T-cells in a patient’s tumor,” said Mike Burgess, M.D., Ph.D., President of R&D at Turnstone. “It represents the most straight-line solution for broadening the benefit of TILs to other solid tumor indications while maintaining commercial feasibility. We are excited to advance this technology both independently and in combination with our viral immunotherapies.”
Click here for more on mergers, acquisition and business news
Collated by : Richa Tewari, PhD
Editors' Desk
Richa Tewari, PhD
Oncology News
Esha Sehanobish, PhD
MedNess Plus
Arundithi Ananthanarayanan
MedNess Reviews
Divyaanka Iyer
BioPharma News
Shilpa Rawal, PhD
Onco I-Analyse
Debarati Banik
HealthIT
Rinki Saha
BioPharma News
Abhi Dey
Consulting Editor
Nisha Peter, PhD
Managing Editor
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The editors take care to share authentic information.  In case of any discrepancies please write to medness.newsletter@gmail.com
The sponsors do not have any influence on the nature or kind of the news/analysis reported in MedNess. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of Medness. Examples of analysis performed within this article are only examples. They should not be utilized in real-world analytic products as they are based only on very limited and dated open source information. Assumptions made within the analysis are not reflective of the position of anyone volunteering or working for Medness. This blog is strictly for news and information. It does not provide medical advice, diagnosis or treatment nor investment suggestions. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
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Content Editors: Richa Tewari , Esha Sehanobish , Rinki Saha ,  Shilpa Rawal, PhD ,  Debarati Banik  , Divyaanka Iyer , Arundithi Ananthanarayanan and Abhinav Dey 
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