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MedNess: bite-size biopharma and medtech news

24th March
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MedNess This Week
HIGHLIGHTS
     Onco-I-Analyse
Merck KGaA suffers another setback for bintrafusp alfa
On 16th January, Merck KGaA announced that the Phase II INTR@PID BTC 047 trial of bintrafusp alfa, TGFβxPD-L1 bispecific antibody, as second line treatment in locally advanced or metastatic biliary tract cancer (cholangiocarcinoma and gallbladder cancer) failed to meet its primary endpoint of ORR.
Background: Biliary tract cancers form in the cells of the bile ducts, gallbladder or ampulla of Vater. These are rare, aggressive GI tumors with poor prognosis and 5-year survival rate of only 2% for metastatic cancers. Chemotherapy is the standard of care for frontline BTC with very limited options following progression and low response rates of ~6% with immunotherapies.
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.
Details: The study evaluated bintrafusp alfa monotherapy in 159 BTC patients who had progressed or were intolerant to frontline 1L systemic platinum-based chemotherapy. Although, the asset demonstrated an IRC-adjudicated ORR of 10.1%, the study did not meet the prespecified threshold for regulatory submissions with the authorities.
After >9 months of follow-up, bintrafusp alfa showed efficacy and durability with a tolerable safety profile. Detailed results are expected to be published or presented during an upcoming medical meeting.
Implications: Bintrafusp alfa has been one of the leading assets for GSK and Merck KGaA alliance and therefore, further subdues their oncology ambitions. Almost 2 months ago, Merck KGaA had discontinued the H2H Phase III INTR@PID Lung 037 trial of bintrafusp alfa against pembrolizumab as 1L treatment in high PD-L1 expressing advanced NSCLC for futility in PFS.
Although these results cast further doubts on the asset’s future, Merck continues to evaluate it across several tumors, including 1L BTC as part of the INTR@PID Clinical Trial Program – BTC (Ph II/III - 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).
Collated by : Shilpa Rawal, PhD
COVID Special
FDA authorizes the first machine learning-based non-diagnostic screening device for COVID-19 
FDA recently authorized the first machine learning-based non-diagnostic device that will identify certain biomarkers that may be indicative of COVID-19 infection. For example, it will help in identifying biomarkers for hypercoagulation. The EUA for the device, Tiger Tech COVID Plus Monitor was granted to Tiger Tech Solutions, Inc. It should not be used to diagnose or exclude the COVID-19 infection since underlying conditions of an individual may interfere with the COVID-19 related performance of the device producing incorrect screening results. It can be used on individuals without a fever. The device is not intended to be used in those with symptoms of COVID-19 and is not a substitute for a diagnostic test for determining COVID-19. 
The Tiger Tech COVID-19 Plus Monitor can identify certain biomarkers that may indicate COVID-19 as well as some other hyper-inflammatory states caused by allergic reactions and hypercoagulable conditions such as cancer or sepsis. Hypercoagulation is a common abnormality in COVID-19 patients. It can detect these in asymptomatic subjects who are over the age of 5 years. The Tiger Tech COVID-19 Plus Monitor includes an arm band with embedded light sensors and a small computer processor. The arm band is wrapped around the left arm below the elbow. The sensors obtain signals from blood flow over a period of three to five minutes. After the measurement, the processor obtains information such as pulse rates which are then fed into probabilistic machine learning model trained to make predictions on whether the signals are representative of hypercoagulation in blood. Different colored lights indicate if an individual is demonstrating biomarkers or if the results are inconclusive. The EUA was granted based on data from a validation study conducted in hospital and school settings. 467 asymptomatic individuals including 69 confirmed positive cases were enrolled in the study. Tiger Tech COVID-19 Plus monitor had a positive percent agreement of 98.6% and a negative percent agreement of 94.5%. This was the data from the hospital study. The data from the school study also showed similar results. 
“The FDA is committed to continuing to support innovative methods to fight the COVID-19 pandemic through new screening tools,” said Jeff Shuren, M.D., J.D., director of FDA’s Center for Devices and Radiological Health. “Combining use of this new screening device, that can indicate the presence of certain biomarkers, with temperature checks could help identify individuals who may be infected with the virus, thus helping to reduce the spread of COVID-19 in a wide variety of public settings, including healthcare facilities, schools, workplaces, theme parks, stadiums and airports.” 
Sanofi and Translate Bio announce the initiation of the Phase 1/2 clinical trial for their COVID-19 mRNA candidate vaccine
 Translate Bio and Sanofi Pasteur recently announced the initiation of the Phase 1/2 clinical trial of their COVID-19 candidate mRNA vaccine, MRT5500. Interim results from this trial will be available in the third quarter of this year. The preclinical studies to determine the effectiveness of the vaccine in inducing neutralizing antibodies, is still ongoing. The data so far has shown that two immunization of the mRNA vaccine induced high antibody levels comparable to the upper range of those seen in humans. Following the preclinical data, the Phase 1/2 clinical trial will be a double blind, randomized, placebo-controlled trial that will determine the safety, tolerability and immunogenicity of the candidate vaccine. A total of 415 healthy adults, 18 years and older will be recruited for this study. The study will be conducted across 13 sites. The recruited participants will receive a dose of the MRT5500 vaccine or two doses in 21 days. Dose levels of 15, 45, or 135-microgram will be investigated. The companies are aiming at a temperature of -20 degree Celsius for storage. They will also try to store it a 2-8 degree Celsius. 
“We have made important progress towards developing mRNA vaccine candidates for infectious diseases through our collaboration with our partner Sanofi Pasteur,” said Ronald Renaud, Chief Executive Officer of Translate Bio. “With the impact of mRNA vaccines demonstrated during the pandemic, our joint development team remains steadfast in our commitment to advancing MRT5500 as part of the collaborative effort to overcome this global health crisis.” “Our mRNA vaccine candidate is the result of our expertise in infectious diseases coupled with the innovative technologies of our partner,” said Thomas Triomphe, Executive Vice President and Global Head of Sanofi Pasteur. “Initiating the Phase 1/2 trial represents an important step forward in our goal of bringing another effective vaccine to the ongoing fight against the COVID-19 pandemic.”
Click here for more COVID news
Collated by : Esha Sehanobish, PhD
    Drug Approvals
European Commission Approves Expanded Indication for KEYTRUDA® in Adult and Pediatric Patients With R/R Classical Hodgkin Lymphoma (cHL)
“The European Commission’s approval of an expanded use of KEYTRUDA provides another option for adult and pediatric patients with classical Hodgkin lymphoma who have disease progression after earlier lines of therapy or relapse after transplantation,” said Dr. Vicki Goodman, vice president, clinical research, Merck Research Laboratories. “We are driven to advance therapies to help improve outcomes for patients with blood cancers, including those with relapsed or refractory classical Hodgkin lymphoma, through our broad clinical program.”
FDA Approves radioembolization treatment TheraSphere™ Y-90 Glass Microspheres for HCC patients
"I am honored to have spearheaded the LEGACY trial in which we found that patients with early and advanced HCC exhibited very high response rates as well as clinically meaningful durations of response and survival, establishing TheraSphere as a standard treatment for this patient population," said Riad Salem, M.D., M.B.A, interventional radiologist at Northwestern Memorial Hospital and principal investigator of the LEGACY trial. "The trial results, which have been accepted for publication in Hepatology, produced one of the most comprehensive databases for TheraSphere, empowering physicians to make informed, data-driven decisions for their patients."
Regulatory News
Priority Review From FDA for New Drug Application for HIF-2α Inhibitor Belzutifan (MK-6482) in Patients With Von Hippel-Lindau Disease-Associated RCC
“Von Hippel-Lindau disease is a rare genetic condition for which there is no systemic treatment option available and is associated with a high risk of cancer development in multiple organs. In fact, up to 70% of patients with VHL develop renal cell carcinoma during their lifetime,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “This priority review validates the important progress we have made to expand and diversify Merck’s oncology pipeline with innovative, new therapeutic approaches. We look forward to working closely with the FDA to bring belzutifan to patients in need.”
Trial Results
IDMC announces early stopping of Ph 3 trial of Libtayo® (cemiplimab) monotherapy vs chemotherapy in chemotherapy-treated recurrent or metastatic cervical cancer patients based on OS benefit
"Libtayo monotherapy is the first medicine to demonstrate an improvement in overall survival in women with recurrent or metastatic cervical cancer following progression on platinum-based chemotherapy in a Phase 3 trial," said Krishnansu S. Tewari, M.D., Professor and Director of the Division of Gynecologic Oncology at the University of California, Irvine and a trial investigator. "This landmark clinical achievement will bring hope to women with advanced cervical cancer who are often younger than patients with other cancers. This is reflected in this trial where the average age was 51."
FAILED TRIAL: Ph 3 ILLUMINATE-301 trial of tilsotolimod + ipilimumab vs ipilimumab alone in anti-PD-1 refractory advanced melanoma patients did not meet its primary endpoint of ORR
 “We are surprised and disappointed that the response data from ILLUMINATE-301 do not lead us to an accelerated path to a new and much-needed treatment option for these patients,” stated Vincent Milano, Idera’s Chief Executive Officer. “We would like to extend our deepest gratitude to everyone involved in this study, especially the many courageous patients who participated and continue in follow up.”
Click here for more Trial Results
Trial/Program Status
Durvalumab immunotherapy proceeds to Ph 3 DREAM3R trial for malignant pleural mesothelioma in the US, Australia, and New Zealand
“DREAM3R will determine if concurrent chemo-immunotherapy can improve outcomes in malignant pleural mesothelioma, especially for the majority of patients with the epithelioid subtype,” said lead US investigator Patrick Forde, MD, of Johns Hopkins University. “Both the DREAM and PrE0505 phase 2 trials showed remarkable results in MPM with the combination of chemotherapy and durvalumab, and warrant confirmation in a randomized phase 3 trial.”
Ph 1b Trial of Relacorilant + Keytruda® Initiated in Patients with Adrenal Cancer with Cortisol Excess
“Cortisol activity blunts the cancer-killing attributes of immunotherapeutic agents such as checkpoint inhibitors,” said Andreas Grauer, MD, Corcept’s Chief Medical Officer, “which may be why pembrolizumab is rarely effective as monotherapy in patients with adrenal cancer with cortisol excess. Our trial will examine whether adding relacorilant to pembrolizumab therapy will reduce cortisol-activated immune suppression sufficiently to help pembrolizumab achieve its intended tumor-killing effect, while relacorilant treats the Cushing’s syndrome caused by excess cortisol activity.”
Click here for more Trial Statuses
Collated by : Richa Tewari, PhD
MedNess Plus
FDA accepts the supplemental Biologics License Application (sBLA) for Dupixent as an add-on treatment for children with moderate-to-severe asthma 
FDA accepted for review the sBLA for Dupixent (dupilumab) as an add-on treatment for children with uncontrolled moderate-to-severe asthma. The target age-group is six to 11 years. It has so far been approved as an add-on treatment for patients with the same condition but those who are aged 12 years or older with increased levels of eosinophils. These patients also have an increased dependence on oral corticosteroids for asthma treatment. The target action date for the current new sBLA is planned for the first quarter of 2021. 
Dupixent (dupilumab) is a fully human monoclonal antibody that functions by inhibiting the signalling of both interleukin-4 (IL-4) and interleukin-13 (IL-13) that are key drivers of type-2 inflammation. Type 2-inflammation is a major factor in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis and eosinophilic esophagitis. The sBLA submission was based on data from a pivotal Phase 3 study. This Phase 3 study was evaluating the safety and efficacy of Dupixent in addition to the standard-of-care maintenance therapy in children with mild-to-moderate asthma with type 2 inflammation. It is usually characterized by increased fractional exhaled nitric oxide and eosinophil levels. Dupixent was able to significantly reduce severe asthma attacks and also rapidly improved lung function within a period of two weeks in children belonging to the age group of six to 11 years. The safety profile is similar to that established for Dupixent in the approved indication for those who are 12 years and older. Some of the adverse effects associated with the administration of Dupixent included viral upper respiratory tract infections and eosinophilia. Sanofi and Regeneron are currently studying Dupixent in a variety of diseases driven by type 2 inflammation.
FDA accepts for Priority Review Pfizer’s Biologic License Application for TicoVacTM, its tick-borne encephalitis vaccine 
FDA recently accepted for Priority Review, Pfizer’s Biologics License Application (BLA) for their tick-borne encephalitis (TBE) vaccine, TicoVacTM. This vaccine is used for active immunization to prevent TBE in individuals one year and older. The FDA will target an action date within six months of the date of application. The Prescription Drug User Fee Act (PDUFA) is anticipated for August 2021. If approved, the vaccine will be the first one to be approved in the US to protect children and adults who are prone to being infected by TBE. 
Tick-borne encephalitis (TBE) is an infection that affects the spine and the brain. It is transmitted via the bite of an infected tick. Under certain circumstances it can be mistaken as flu. But it may have possible long-term effects. It is less frequently transmitted by ingestion of unpasteurized milk or milk products from infected animals. Some of the long-term effects include paralysis, muscle weakness and cognitive changes. TBE can affect individuals of all ages. TBE has been reported in more than 35 countries throughout the world. Currently, there is no cure for TBE. It can be managed only by managing the symptoms of the infection. TicoVacTM is an inactivated whole virus vaccine that uses a seed virus similar to TBE found in nature. The vaccine is therefore capable of inducing neutralizing antibodies against the natural TBE virus since the inactivated virus incorporated is similar in sequence and structure. The current BLA application is based on results from more experience and also from clinical trials that have been designed to determine the safety and immunogenicity of the vaccine across age groups 1-15 years and 16-65 years. The pooled seropositivity rates were 99-100% in 1-15 years group and 94-99% in the 16-65 years group following three doses. The vaccine was also well-tolerated with no serious adverse effects. In those who have had at least two doses, the vaccine has been shown to be 96-99% effective. Two to three doses of the vaccine have been shown to be enough to generate a long-lasting immune memory. 
“For many years, our TBE vaccine has helped protect millions of people in Europe from this potentially serious disease. We are proud that today's US FDA priority review acceptance acknowledges the potential value that our vaccine candidate can bring,” said Nanette Cocero, PhD, Global President, Vaccines, Pfizer Inc. “If approved in the US, we hope this vaccine will help protect those traveling to or residing temporarily in at-risk locations, potentially including military personnel who are serving overseas.”
Click here for more MedNess Plus
Collated by : Esha Sehanobish, PhD
MedNess @ HealthIT
 
Eye-tracking technology is gaining traction in healthcare
We have had the long-established technology of using eye-tracking for personal identification in security systems, with hardware and software systems continuously evolving to progress into other industries. A common use in the healthcare industry has been assistive technology solutions through eye tracking to support the communication and computing needs of severely handicapped individuals. More recently, the complexity and how it can offer a rare window into brain functions is being revealed to the scientists. This has led them to test eye-tracking as a non-invasive method of diagnosis for brain injury, autism, and other learning/developmental, as well as use it as a diagnostic tool for neurodegenerative conditions such as Alzheimer’s, dementia, Huntington’s, and Parkinson’s. Recent impact of this technology includes alternative and augmentative communication (AAC) platforms and speech generating devices (SGD): utilizing eye tracking in non-verbal patients with conditions such as cerebral palsy, autism, ALS, muscular dystrophy, stroke, traumatic brain injuries, spinal cord injuries, and Rett syndrome. By gazing through a virtual keyboard, these patients can generate speech. The technology has come in handy to establish communication with the intubated patients during the most recent COVID-19 era. In summary, by measuring how the eyes move, track, and focus, precision eye-tracking technology is now able to combine AI algorithms to detect and identify underlying conditions, as well as facilitating patient communication.
Genetic testing used successfully to prescribe safe blood-thinner
Blood thinners, anti-platelet drugs are used to prevent complications from blood clotting after a procedure to open clogged arteries. Moreover, clinicians often prescribe patients with coronary artery disease clopidogrel to reduce the risk of ischemic events, including blood clots, stroke, heart attack, recurrent chest pain, and death following a percutaneous coronary intervention or stent placement. The other major agents used in this respect are ticagrelor and prasugrel. In a recent study published in JACC: Cardiovascular Interventions, researchers compared people who were treated with the newer anti-platelet agents ticagrelor or prasugrel against clopidogrel treated patients. The team evaluated data about the effect of the CYP2C19 gene on ischemic events in nearly 16,000 people. The meta-analysis involved 1,000+ research studies, including several randomized clinical trials. One of the trials was TAILOR-PCI, a large study funded by the Mayo Center for Individualized Medicine and the National Heart, Lung, and Blood Institute (NHLBI). According to this study, genetic variants of CYP2C19, which leads to its functional loss, may interfere with the body’s ability to metabolize, and activate clopidogrel, meaning patients with these variants would better tolerate and benefit from the other anti-platelet medications. According to Naveen Pereira, MD, a Mayo Clinic cardiologist, and the first and corresponding author of the mentioned study, clopidogrel can safely be given to approximately 70 percent of patients with coronary artery disease following percutaneous coronary intervention, as their data suggests. Given the fact that Clopidogrel is less costly, accepted by most insurance companies in the US, and carries fewer side effects like shortness of breath and bleeding, the study linking genetic testing to the application of blood thinner can be useful, and pave the way to similar studies in the future.
MedNess Business
Exelixis, Merck and Pfizer to Evaluate XL092 and Avelumab in Various Forms of Locally Advanced or Metastatic Urothelial Carcinoma
“We are pleased to collaborate with Merck KGaA, Darmstadt, Germany and Pfizer to study the potential of XL092 in combination with avelumab as part of the broad development program evaluating our novel next generation tyrosine kinase inhibitor across a wide variety of cancers,” said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. “Although several therapies are now available to treat bladder cancers, the prognosis for patients with advanced disease remains poor and more options are needed. Evaluating how XL092 may positively impact care when paired with immunotherapy is central to our goal of improving therapeutic outcomes for patients with this and other difficult-to-treat cancers.”
Bicara Therapeutics launched today with a $40 million investment from Biocon Limited
“Immune checkpoint inhibitors and targeted therapies have been important advances in cancer care — but unfortunately, far too many patients either fail to respond or stop responding as their tumors grow resistant. Our dual-action biologics have the potential to bring new hope to these patients,” said Claire Mazumdar, Ph.D., MBA, Chief Executive Officer of Bicara Therapeutics. “We have brought together a team with deep experience in engineering complex biologics and a successful track record of developing FDA-approved drugs, and we’re thrilled to be advancing through the clinic so quickly as we move with urgency to address the significant need for more effective cancer treatments.”
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
Managing Editor
Shalini Roy Choudhury
Managing Editor
Nisha Peter, PhD
Consulting Editor
Abhi Dey
Consulting 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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