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MedNess: bite-size biopharma and medtech news

7th October, 2020
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HIGHLIGHTS
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Onco I-Analyse
BMS’ Opdivo + Yervoy approved by the FDA as the first and only immunotherapy for previously untreated MPM
On October 02, US FDA granted approval to Opdivo + Yervoy combination for 1L treatment of adult patients with unresectable malignant pleural mesothelioma (MPM). The approval was based on the pre-specific interim analysis of the Ph III CHECKMATE-743 trial, which evaluated the combination against the platinum-based standard of care (SoC) chemotherapy. The interim analysis demonstrated significantly superior OS of 18.1 vs. 14.1 months for the Opdivo + Yervoy arm vs. SoC (HR: 0.74; p=0.002); while OS @ 2-years was 41% vs. 27%. Although, OS benefit was observed across various subgroups, no improvements were observed in key secondary endpoints of PFS (BICR review) and ORR.
The sBLA was reviewed under the FDA’s Real-Time Oncology Review (RTOR) pilot program and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The approval was granted within 6 weeks of submissions, which was nearly 5 months ahead of the goal date. The application was also conducted under the FDA’s Project Orbis, which enables simultaneous review of application by additional regulatory authorities - Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Switzerland’s Swissmedic.
Mesothelioma is a rare and aggressive cancer with poor prognosis. Chemotherapy is the backbone SoC with np other approved therapies till date. Although, NCCN does recommend Avastin for frontline and Keytruda, Opdivo + Yervoy as treatment options for subsequent lines. This approval is hallmark as it marks the first approval in MPM in over 15 years in this patient population. FDA’s last approval was in 2004 for pemetrexed + cisplatin in 1L-MPM. Additionally, this is the 3rd indication for Opdivo + Yervoy-based treatments in thoracic cancers.
All other three key immunotherapy agents (Imfinzi, Keytruda and Tecentriq) are also being evaluated in various combinations as treatment options for frontline MPM.
Collated by :Shilpa Rawal, PhD
COVID Special
The antibody cocktail from Regeneron showed improved symptoms and reduced viral levels in non-hospitalized patients with COVID-19
Regeneron Pharmaceuticals recently released data from their ongoing seamless Phase 1/2/3 trial of the investigational antibody cocktail, REGN-COV2. The data showed positive results in reducing the viral levels and showed improvements in symptoms in non-hospitalized COVID-19 patients. It also showed a reduction in medical visits in such patients. This is a subsection of a larger ongoing program that will investigate the effectiveness of REGN-COV2 in the prevention of COVID-19 infection in people with possible exposure to the virus and will also determine its effectiveness in the treatment of hospitalized patients.
"After months of incredibly hard work by our talented team, we are extremely gratified to see that Regeneron's antibody cocktail REGN-COV2 rapidly reduced viral load and associated symptoms in infected COVID-19 patients," said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron. "The greatest treatment benefit was in patients who had not mounted their own effective immune response, suggesting that REGN-COV2 could provide a therapeutic substitute for the naturally-occurring immune response. These patients were less likely to clear the virus on their own, and were at greater risk for prolonged symptoms. We are highly encouraged by the robust and consistent nature of these initial data, as well as the emerging well-tolerated safety profile, and we have begun discussing our findings with regulatory authorities while continuing our ongoing trials. In addition to having positive implications for REGN-COV2 trials and those of other antibody therapies, these data also support the promise of vaccines targeting the SARS-CoV-2 spike protein."
Johnson and Johnson announce the initiation of the global Phase 3 clinical trial of Janssen’s COVID-19 vaccine candidate, JNJ-78436735
Based on the results from the Phase 1/2a trial, Johnson and Johnson recently announced the initiation of their pivotal, multi-center Phase 3 trial, ENSEMBLE, for Janssen Pharmaceutical’s vaccine candidate, JNJ-78436735. The vaccine candidate makes use of the company’s AdVac® technology platforms which has previously been used for the development of vaccines and candidate vaccines against other viruses. The vaccine developed based on this technology should be stable for two years if kept at -20 deg Celsius and for at least three months at 2-8 degree Celsius.
“As COVID-19 continues to impact the daily lives of people around the world, our goal remains the same – leveraging the global reach and scientific innovation of our company to help bring an end to this pandemic,” said Alex Gorsky, Chairman and Chief Executive Officer, Johnson & Johnson. “As the world’s largest healthcare company, we are bringing to bear our best scientific minds, and rigorous standards of safety, in collaboration with regulators, to accelerate the fight against this pandemic. This pivotal milestone demonstrates our focused efforts toward a COVID-19 vaccine that are built on collaboration and deep commitment to a robust scientific process. We are committed to clinical trial transparency and to sharing information related to our study, including details of our study protocol.”
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Collated by : Esha Sehanobish, PhD
Regulatory News
FDA places IND for live-cell encapsulation technology, Cell-in-a-Box®, on hold
PharmaCyte’s Chief Executive Officer, Kenneth L. Waggoner, said, “The decision by the FDA to place our IND application on hold was a deep disappointment to all of us at PharmaCyte; however, we are grateful that the FDA didn’t reject our IND application and we will have an opportunity to address their concerns. I know our many colleagues, who have worked so hard over the years to try to get our treatment ready for clinical use in patients with locally advanced inoperable pancreatic cancer in the hope that we can fulfill an unmet clinical need for such patients, are also disappointed, but we all welcome the opportunity to continue to engage with the FDA to further our treatment.
Fast Track Designation granted to Eganelisib in Combination with a Checkpoint Inhibitor and Chemotherapy for 1L mTNBC
“Fast Track designation is an exciting regulatory milestone that bolsters our momentum in TNBC,” said Adelene Perkins, Chief Executive Officer and Chair of Infinity Pharmaceuticals. “TNBC remains the deadliest form of breast cancer, and there is tremendous need to expedite the development of new treatments that have the potential to improve outcomes in these patients. We believe that adding eganelisib on top of standard of care in a novel triple combination front-line regimen with Tecentriq® and Abraxane® has the potential to provide meaningful benefits to patients and are particularly encouraged by the early signals of clinical activity we have seen in MARIO-3 to date. We look forward to presenting these important data later this year.”
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Trial Results
Failed trial: Ph 3 CheckMate-915 trial of Opdivo + Yervoy versus Opdivo in resected stage IIIb/c/d/IV melanoma patients did not meet co-primary endpoint of significant RFS improvement
“We are proud of our legacy in melanoma with both Opdivo and Yervoy. They have each brought significant benefit as monotherapies for appropriate melanoma patients in the adjuvant setting, and as a dual immunotherapy regimen in the metastatic setting. In CheckMate -915, we evaluated adding Yervoy to Opdivo against Opdivo – an established, active comparator and current standard of care in the adjuvant setting. We designed this study to determine if dual immunotherapy has the potential to bring additional benefits to patients in this setting, understanding the high benchmark we would need to exceed with this trial,” said Sabine Maier, M.D., vice president, Head of Oncology Clinical Development, Bristol Myers Squibb. “We remain committed to continued research in melanoma, both to further understand the potential benefit of Yervoy in combination with Opdivo to treat high-risk melanoma patients in the earlier stages of disease, as well as to study additional novel combinations in various settings.”
Results of Additional Secondary Endpoint of Castration Resistance-Free Survival from Ph 3 HERO Study of Relugolix in Advanced Prostate Cancer Announced; Key Secondary endpoint not met
“These new data from the Phase 3 HERO study show that three out of four men with metastatic prostate cancer remained castration resistance-free through 48 weeks while on oral relugolix, in-line with leuprolide acetate injections, the current standard of care,” said Dan George, M.D., a professor of medicine and surgery at the Duke University School of Medicine and HERO program steering committee member. “I continue to be excited by relugolix as a potential new and differentiated treatment option for men with prostate cancer given its robust clinical and safety data, including the lower risk of major adverse cardiovascular events compared to leuprolide acetate.”
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Trial/Program Status
First patient dosed in Ph 3 study of xevinapant (Debio 1143) + CRT vs placebo in high-risk patients with LA-SCCHN
“The launch of the TrilynX trial follows several key 2020 milestones in the development of xevinapant including the FDA Breakthrough Designation in February and the recent presentation this fall of our clinically meaningful 3-year, phase II data at the ESMO (European Society of Medical Oncology) virtual congress. We expect that this large-scale trial will confirm the strong outcomes observed in phase II, bring us a step further towards positively impacting the lives of high-risk head & neck cancer patients.” – Bertrand Ducrey, CEO of Debiopharm.
Click here for more Trial Status
Collated by : Richa Tewari, PhD
Medness Plus
FDA approves Nucala for the treatment of hypereosinophilic syndrome in children 12 years or older in nearly 14 years
FDA recently approved meplizumab (Nucala) for the treatment of hypereosinophilic syndrome (HES) in children 12 years and older. The treatment is deemed to be safe for six months or longer without another identifiable non-blood related cause of the disease. Nucala received a fast track designation and a priority review based on which FDA will have to take an action within a short period of time. It was also granted an orphan drug designation that provides incentives for the development of drugs for the treatment of rare diseases. Nucala has already been approved for the treatment of patients with severe eosinophilic asthma in patients 6 years and older and for the treatment of adults with eosinophilic granulomatosis with polyangiitis.
“Today’s approval marks the first time in over a decade that there is a new FDA-approved treatment option for patients with hypereosinophilic syndrome,” said Ann Farrell, M.D., director of the Division of Nonmalignant Hematology in the FDA’s Center for Drug Evaluation and Research. “FDA is committed to helping develop safe and effective treatment options for this group of rare and debilitating blood diseases and other rare conditions.”
FDA approves SIMPONI ARIA® for the treatment of an active form of juvenile idiopathic arthritis and extends the indication for Psoriatic Arthritis in patients 2 years and older
FDA recently approved SIMPONI ARIA® (golimumab) for the treatment of patients two years and older with active polyarticular juvenile idiopathic arthritis (pJIA) and has extended the psoriatic arthritis (PsA) indications in the patient population of the same age group. SIMPONI ARIA® has already been approved in the US for the treatment of adults with moderate to severe active rheumatoid arthritis, active PsA and ankylosing spondylitis. For pediatric patients, SIMPONI ARIA® will be used on a body surface (BSA)- based dosage regimen of 80 mg/m2 and will be administered intravenously over 30 minutes at week 0, 4 and every 8 weeks thereafter.
“This latest FDA approval of SIMPONI ARIA for pediatric use in active pJIA and active PsA not only brings a new option to young patients living with these diseases but also adds to the growing body of evidence for this treatment,” said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. “For more than 20 years, we at Janssen have been committed to researching anti-TNF biologic agents for immune-mediated diseases and are encouraged to expand treatment options for these patients.”
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Collated by : Esha Sehanobish, PhD
Medness @ HealthIT
PTSD assessment made simpler through machine learning
Machine learning has helped researchers to make the assessment for post-traumatic stress disorder (PTSD) less complicated by cutting down some of the questions that are diagnostic of the condition. Although prevalently experienced by the war veterans, the cases of PTSD within the general population is also in the rise, totaling almost 8 million within the US alone. Researchers from VA Boston Healthcare System and the Boston University School of Public Health (BUSPH) set out to streamline the process through machine learning to cut down on the existing assessment time of 30 minutes, and used the data source of Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (SCID-5) containing assessments of 1,265 war veterans serving in Iraq and Afghanistan. They were able to cut 6 items from the list of assessment, while identifying detachment or estrangement from others to be one of the common elements within both men and women suffering from PTSD. Curiously, the machine learning tools also revealed that different items are important when diagnosing men and women. In addition, the researchers admit that despite providing companion tools for PTSD assessment, machine learning is not going to replace human providers by any capacity. 
Improving cardiovascular health through machine learning
Researchers from MIT (CSAIL: Computer Science and Artificial Intelligence Laboratory) have developed a machine learning tool to detect a common warning sign of acute heart failure, that is, the severity of accumulation of excess fluid in patients’ lungs (pulmonary edema). The main framework of the assessment was to build a scale from 0 to 3 (0 being healthy, 3 being the worst) and training the system with 300,000 X-ray images and corresponding notes from radiologists. Because of the variability of tones and elaborations in the radiologists’ notes from different sources, the researchers also had to build a set of linguistic rules and substitutions to maintain consistently across reports. The outcome from the system was efficient enough to diagnose the right level of excess fluid with accuracy in more than 50% cases, and also correctly diagnosed level 3 cases in almost 90% cases. According to the team, ability for the system to extract the information from both image-data and texts of the reports was a win. The system will be integrated in Beth Israel Deaconess Medical Center’s emergency room workflow this fall. 
Medness Reviews

Focused ultrasound wave induces targeted drug delivery inside the brain with millimeter precision
Most clinically available small-molecule neurological drugs (400 to 500-Da) reach the brain via passive diffusion across the blood-brain barrier (BBB). This absorption can often lead to significant off-target effects as most of the drugs binds to the receptor binding sites in other brain regions apart from the affected area. On the other hand, deep-brain stimulation and transcranial magnetic stimulation do not provide cellular or molecular specificity. To address this long-term challenge, scientists from the Switzerland Neuroscience Center, have developed a unique drug delivery system by utilizing Aggregation and Uncaging Focused Ultrasound Sequence (AU-FUS) at the specific target area within the brain. In short, they injected drug-encapsulated liposomes tethered to ultrasound-sensitive microbubbles (with perfluorocarbon gas core) into the bloodstream.
The focal drug delivery method is comprised of two steps. The researcher used the low energy ultrasound waves to create the drug aggregates at the desired brain location. Next, a higher level of ultrasound energy to get the drug carriers to vibrate at this site. Shear forces destroy the lipid membranes around the drugs, releasing the drugs to the target site where it could be absorbed by the nerve tissue. The team has also successfully tested this delivery method in vivo in rat brains by injecting the lipid encapsulated drug into the tail vein. The small molecule drug was released in the affected area without affecting the BBB. 
The advantages of this new drug delivery technique are multifaceted as it does not impact BBB and causes no substantial tissue inflammation because of the usage of lower energy levels. The researcher also claimed that this delivery system only needs 1,300 times smaller dose than the typically approved drug dose. Right now, this technique is being standardized so that it could become the most useful therapeutic strategy to treat a neurological disorder.
Collated by :  Rinki Saha 
Medness Business
Onco-News

Celyad Oncology and Merck to Evaluate CYAD-101 + KEYTRUDA® (pembrolizumab) in Microsatellite Stable mCRC patients
“We are extremely pleased to enter into this clinical collaboration with MSD, as we believe the mechanism of actions of CYAD-101 and KEYTRUDA are highly complementary and could help to drive meaningful clinical benefit in patients with advanced metastatic colorectal cancer, in particular with microsatellite stable disease where a high unmet medical need exists” said Filippo Petti, Chief Executive Officer of Celyad Oncology. “In addition, the collaboration with MSD adds an important dimension to our clinical program for CYAD-101 for the treatment of mCRC and provides us with the opportunity to build upon the encouraging clinical activity we’ve reported to date from the ongoing alloSHRINK trial.”
Pfizer to invest $200 million in CStone shares and license sugemalimab (CS1001, PD-L1 antibody) in mainland China
“Pfizer’s investment in CStone is a statement of its confidence in the potential of our anti-PD-L1 treatment and recognition of our research and development capabilities,” said Frank Jiang, M.D., Ph.D., Chairman and Chief Executive Officer of CStone. “By joining forces with Pfizer and leveraging its commercialization infrastructure, we will ensure that patients across a vastly expanded number of markets in China have quicker access to our highly differentiated PD-L1 treatment. In addition, we have advanced our transformation into a full-fledged biopharmaceutical company by forging a collaboration that will enable us to accelerate development and commercialization of globally innovative therapies for Chinese patients.”
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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 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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