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MedNess: bite-size biopharma and medtech news

12th May, 2021
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MedNess This Week
HIGHLIGHTS
Onco-I-Analyse
Merck’s Keytruda receives accelerated approval for frontline, HER2+ gastric cancer
On 5th May, the US FDA granted accelerated approval to Keytruda in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy as a frontline treatment option for locally advanced unresectable or metastatic HER2+ gastric or gastroesophageal junction (GEJ) adenocarcinoma. The approval was based on interim results from the Phase 3 KEYNOTE-811 study.
Background: Gastric cancer (GC) is aggressive cancer, with a 5-year survival rate of only 5.5% for metastatic GC. It is the third most common cause if death by cancer worldwide. Evidence suggests that PD-1 and PD-L1 are highly expressed in gastric cancer cells thereby representing promising targets for the treatment of gastric cancer.
Details: The approval was based on data of key secondary endpoints from the Phase 3 KEYNOTE-811 study evaluating Keytruda + trastuzumab + chemotherapy (FP or CAPOX) vs. trastuzumab + chemotherapy as first-line therapy in HER2+ GC or GEJ adenocarcinoma. Prespecified interim analysis included initial 264 randomized patients.
Keytruda arm demonstrated significantly superior ORR of 74% (CR: 11%, PR: 63%) vs. 52% (CR: 3.1%, PR: 49%) in patients not receiving Keytruda (P<0.0001). The median duration of response was 10.6 vs. 9.5 months in Keytruda versus the control arm, respectively. 65% vs. 53% showed response for ≥6 months in Keytruda versus the control arm, respectively. Both arms showed no clinically meaningful differences in grade 3-4 adverse events.
The application was granted priority review and was being evaluated under the FDA’s Real-Time Oncology Review (RTOR) pilot program and the Assessment Aid.
The trial is still enrolling patients for a target of 732 patients and evaluating primary endpoints of PFS and OS.
Implications: The accelerated approval is contingent based on sustained clinical benefit in the confirmatory trials. The approval comes somewhat surprisingly after FDA’s ODAC voted against maintaining the accelerated approval for Keytruda as 3rd line treatment for PD-L1+ GC or GEJ adenocarcinoma patients.
Last month, the FDA approved Opdivo + chemotherapy as the first immuno-oncology regimen in 1L GC. Although the trial excluded HER2+ patients, both PD-1 inhibitors stand to compete against each other based on physician preference.
As per an analyst “About 10,000 newly diagnosed gastric/GEJ cancer patients are treated each year in the US, with about a quarter being HER2+. That represents a $300 million opportunity.”
 
Collated by : Shilpa Rawal, PhD
Drug Approvals
Tecentriq approved by European Commission as a first-line monotherapy treatment for people with ALK/EGFR WT, PD-L1+ve mNSCLC
“We are delighted to bring Tecentriq to people in the EU with this specific type of lung cancer,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “Tecentriq monotherapy has been shown to improve overall survival in people with high PD-L1 expression, when compared to chemotherapy, and therefore represents a new treatment option for people living with this difficult-to-treat disease.”
XTANDI™ (enzalutamide) Approved by European Commission for Men with Metastatic Hormone-Sensitive Prostate Cancer
"Metastatic hormone-sensitive prostate cancer patients have limited options and, unfortunately, there is a poor prognosis for many men," said Andrew Armstrong, M.D., Professor of Medicine, Surgery, Pharmacology and Cancer Biology, Director of Research in the Duke Cancer Institute's Center for Prostate and Urologic Cancers and lead investigator of ARCHES. "The research supporting this approval provides clinical evidence showing how enzalutamide can help improve outcomes for men with mHSPC, which gives healthcare professionals in Europe the option to offer the treatment across the advanced prostate cancer disease continuum."
Click here for more Drug Approvals
Regulatory News

Ph 2 CERPASS clinical trial protocol amended to include complete response (CR) rate as a primary endpoint in addition to ORR, and to reduce target enrollment to 180 patients
“Based on the depth and durability of responses and the manageable safety profile we have seen in patients with non-melanoma skin cancers treated with RP1 in combination with Opdivo to date, we are amending the clinical trial protocol for our Phase 2 CERPASS clinical trial to include complete response (CR) rate as a primary endpoint in addition to overall response rate (ORR), and to reduce target enrollment to 180 patients,” said Robert Coffin, Ph.D., President and Chief Research and Development Officer of Replimune. “Incorporating CR as an independent additional primary endpoint should ensure a robust assessment of the clinical meaningfulness of adding RP1 to Libtayo in the primary data analysis upon which a BLA submission and FDA’s assessment for approval will be based.”
FDA Approves IND Application to Develop KRAS G12C Inhibitor JAB21822
"KRAS G12D and KRAS G12V are two exciting programs that cement our position in the top tier of global biotech companies," said Dr. Steve Zhou, Chief Biologist and Senior Vice President of Jacobio. "The R&D of KRAS G12D inhibitors draws on our experience and expertise of the KRAS G12C inhibitor. The combination of various advantages including development experience, coupled with our in-house chemical library and focused library design, as well as small molecule drug development capabilities based on the allosteric inhibitor platform, puts us in a favorable position in the global R&D landscape of KRAS inhibitors."
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Trial Results
Imfinzi and tremelimumab with chemotherapy demonstrated overall survival benefit in POSEIDON trial for 1st-line Stage IV NSCLC
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: “We are pleased to see the POSEIDON Phase III trial demonstrate, for the first time, a significant and clinically meaningful overall survival benefit for Imfinzi plus tremelimumab with chemotherapy in metastatic non-small cell lung cancer. We were particularly pleased by the safety profile. We’ve seen encouraging uptake of novel combinations in this setting and believe this new approach will add a further option for patients with high unmet medical needs. We look forward to discussing the next steps with regulatory authorities.”
Trial/Program Status
Centralized Institutional Review Board Approval Announced for Acclaim-1 Clinical Trial in NSCLC
“The purpose of IRB review is to assure that appropriate steps are taken to protect the rights and welfare of individuals participating as subjects in clinical research,” said Rodney Varner, President and Chief Executive Officer of Genprex. “With this centralized IRB approval, we have achieved another significant clinical milestone. We remain focused on completing our preparations for the Acclaim-1 clinical trial, and look forward to its commencement.”
First Patient Treated in Ph 1/2 Clinical Trial of MCLA-129 in Advanced Lung Cancer and Other Solid Tumors
“The initiation of our phase 1/2 trial of MCLA-129 is an important step in our goal to provide meaningful treatments to patients with cancer, including NSCLC,” said Dr. Andrew Joe, Chief Medical Officer of Merus. “Despite the successes with targeted therapies, patients will often develop resistance to currently approved treatments. Based on our preclinical data and other data, we are excited to investigate MCLA-129 as a potential new treatment option for patients with lung and other cancers, especially those that do not respond to EGFR inhibitors.”
Click here for more Trial Statuses
       MedNess @ HealthIT
Time-efficient COVID test is now aided by AI
The University of Utah (the U) is collaborating with ARUP Laboratories and Techcyte Inc. to forge a rapid  COVID-19 antibody test, aided by artificial intelligence; a five minutes test called NanoSpot.AI. The workflow for the test includes simple steps, such as, a finger prick to collect blood drops into a micro-collection tube, which are then spaced out to three spots on a ready-to-use embossed card. One of the spots displays the test result, while the other two spots are positive and negative controls for the test. Mixing blood spots with a pre-dispensed, dried reagent on the test card, the blood spot undergoes agglutination that indicates COVID-19 antibodies are present. The picture taken by the end user is then sent to NanoSpot.AI’s site, where AI based image analysis tool is used to analyze and confirm the results, promptly conveying the result to the user on their cellphones.
While clinical studies for the kit is underway, the researchers are excited about the large implication of the invention for travelling and immigration purposes. According to Hans Haecker, MD, PhD, a codeveloper of NanoSpot.AI and a professor in the U Pathology Department Division of Microbiology and Immunology, the invention checks the boxes of faster turnaround, inexpensive to use, and simpler portability. According to Mark Astill, ARUP director of Research and Development, “The expertise and experience we bring enabled what may be the first instance of combining seemingly disparate elements to produce a rapid, economical, QR-code-curated, consistent, point-of-care result.” Ben Cahoon, the CEO of Techcyte confirms: “Our platform breaks each blood spot into thousands of features that the AI uses to statistically determine which specimens are positive for SARS-CoV-2 antibodies”.
Alzheimer’s Mouse model shows success of Gene therapy in preserving memory
Alzheimer’s is characterized by misfolded proteins called amyloid plaques and neurofibrillary tau tangles, which impair cell signaling and promote neuronal death. A team from University of California San Diego School of Medicine has used gene therapy to preserve learning and memory in a mouse model of Alzheimer’s. In this approach of gene therapy, researchers used a harmless adeno-associated viral vector to introduce synapsin-Caveolin-1 cDNA (AAV-SynCav1) into the hippocampus region of three-month-old transgenic Alzheimer’s mice, which are genetically modified to exhibit learning deficits at 9 months and memory deficits at 11 months, also molecularly marked by a deficit of Caveolin-1, a scaffolding protein for neuronal membranes.
According to Brian P. Head, PhD, adjunct professor in the Department of Anesthesiology at UC San Diego School of Medicine and research health scientist at the VA San Diego Healthcare System, “Our goal was to test whether SynCav1 gene therapy in these AD mouse models might preserve neuronal and synaptic plasticity in targeted parts of the membrane and improve higher brain function.” The researchers found that hippocampal learning and memory in mice were preserved in 9- and 11-months old mice, as well as the membrane scaffolding protein level, correlated with a reduction in amyloid plaque formation. The team confirms: “These results suggest SynCav1 gene therapy is an attractive approach to restore brain plasticity and improve brain function in AD and potentially in other forms of neurodegeneration caused by unknown etiology”. They are also proceeding on the way of testing SynCav1 gene delivery in other Alzheimer’s models at symptomatic stages as well as in a mouse model of amyotrophic lateral sclerosis, or Lou Gehrig’s disease.
Collated by: Debarati Banik, PhD
Genes and Therapy
CSL Behring acquires uniQure’s investigational gene therapy for haemophilia B
CSL Behring closed an agreement giving it the global commercialization and licensing rights on uniQure’s AMT-06, an investigational gene therapy for haemophilia B. uniQure is presently undertaking the Phase 3 clinical trial which is expected to conclude in March 2025. As part of the deal, uniQure will receive an upfront cash payment of $450 million from CSL Behring and will be eligible for additional royalty payments, as well as up to $1.6 billion if certain regulatory and commercial milestones are met.
Orchard Therapeutics announces positive outcomes for ADA-SCID gene therapy
Orchard Therapeutics announces positive results for their investigational gene therapy OTL-101 for adenosine deaminase severe combined immunodeficiency (ADA-SCID). There was 100% overall survival and ≥95% event-free survival observed at two and three years following one-time treatment with lentiviral hematopoietic stem cell gene therapy.

No accelerated approval for Avrobio’s gene therapy for Fabry Disease
Gene therapy developer, Avrobio no longer plans to seek early approval for their investigational lentiviral gene therapy AVR-RD-01 for Fabry Disease. This is because, very recently the FDA granted full approval for Sanofi’s Fabrazyme, an enzyme replacement therapy for Fabry Disease. This has set limits on accelerated approval of new therapies to treat Fabry Disease unless Avrobio undertakes a larger clinical trial. The company plans to start that trial mid-next year.
  MedNess Reviews

Airway-on-a-chip technology enables COVID-19 drug repurposing
Screening drug molecules in in-vitro cell culture for their efficacy against the SARS-CoV-2 is a challenge as this doesn’t accurately predict how effective the drugs will be in the human respiratory tract. To offer a potential solution to this problem, a team at Harvard University has developed new lung-on-a-chip models and one of the models has already uncovered an existing drug that might be repurposed in fighting COVID-19.
The lung-on-a-chip model created by a team led by Harvard’s Wyss Institute for Biologically Inspired Engineering uses a microfluidic device designed to mimic the human lung airway. Dubbed as the Lung Airway Chip, the device contains two channels: one is filled with air and the other contains human blood vessel cells and liquid that mimics blood flow. The model, which is about the size of a memory stick, grows airway cells types and develops traits similar to the human lung.  Using the device, the team discovered that the antimalarial drug amodiaquine prevented the SARS-CoV-2 virus that causes COVID-19 from entering lung cells. The researchers validated the results in a small-animal model of the virus, they reported their findings in the journal Nature Biomedical Engineering.
For testing their device, the researchers designed a SARS-CoV-2 pseudovirus that expressed the SARS-CoV-2 spike protein, so that they could identify drugs that interfere with the spike protein's ability to bind to human lung cells' ACE2 receptors.
They found that that two antimalarial drugs that generated enthusiasm in the early days of the pandemic—hydroxychloroquine and chloroquine—did not prevent the COVID-19 virus from entering the lungs. But amodiaquine did, as did breast cancer drug toremifene, and infertility drug clomiphene.
The researchers have teamed up with scientists at the Icahn School of Medicine at Mount Sinai to test amodiaquine against hydroxychloroquine in animal models of COVID-19. In addition to reducing viral load by 70%, amodiaquine prevented transmission of the virus 90% of the time, they reported. The drug is now being tested in COVID-19 patients in Africa.
Vikram Sarabhai Space Center Develops Devices to Battle COVID-19
Indian Space Research Organisation’s Vikram Sarabhai Space Centre (VSSC) has developed three different types of mechanical ventilators and an oxygen concentrator to aid COVID-19 care in the battle against the pandemic that is ravaging the country. The devices are expected to be ready for technology transfer by the end of the month for commercial production.
The development of the cost-effective ventilators named Prana, VAU and Svasta based on designs and features started during the first wave in March 2020 and was expedited for the second wave of infections.
SVASTA – short for ‘Space Ventilator Aided System for Trauma Assistance,’ is designed to work without electric power. According to a concept note on the model, the system operates on compressed air and achieves different modes of ventilation through mechanical settings alone.
'PRANA' - standing for ‘Programmable Respiratory Assistance for the Needy Aid’ is based on an Ambu bag (a commercial manual respirator bag). PRANA delivers oxygen-rich air to the patient by automated compression of the Ambu bag using an actuator.
VaU, expanded as 'Ventilation assist Unit, is a dual-mode ventilator that can work with either medical oxygen from the hospital or with ambient air.  The system, based on pneumatic circuit eyes a low-cost, state-of-the art ventilator which can match the high-end, expensive ones in the market.
The VSSC has also developed a portable medical oxygen concentrator called Shwaas. “It is capable of supplying 10 liter enriched oxygen per minute, adequate for two patients at a time,” he said. It enhances the oxygen gas content by selectively separating the nitrogen gas from ambient air through Pressure Swing Adsorption (PSA) which is commonly used for production of oxygen from air, he said.
The Medical Oxygen Concentrator ‘Shwaas' is a portable device capable of continuously delivering enriched levels of oxygen than that present in air to patients with respiratory problems or those requiring oxygen therapy. The device enhances the oxygen content by selectively separating nitrogen gas from ambient air through PSA.
MedNess Business
Onco-News
Exelixis Expands its Biotherapeutics Portfolio with Acquisition of GamaMabs Pharma’s First-in-Class Humanized Antibody Program Against a Novel Oncology Target
“GamaMabs has generated a compelling body of preclinical data supporting the potential of AMHR2 as a target for novel oncology therapies and demonstrated the safety of an anti-AMHR2 monoclonal antibody in human clinical trials,” said Peter Lamb, Ph.D., Executive Vice President, Scientific Strategy and Chief Scientific Officer of Exelixis. “Based on these data, we believe that applying our ADC capabilities to GamaMabs’ panel of antibodies against AMHR2 could yield a promising new addition to our biotherapeutics portfolio. Acquiring GamaMabs’ extensive know-how related to this target, as well as existing drug product and related manufacturing cell lines, will allow us to reduce significantly the development timeline compared with starting an AMHR2 program de novo. This is consistent with our strategy of advancing novel cancer therapies as rapidly as possible in order to enable new treatment options that may provide improved patient benefit.”
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
Managing Editor
Shalini Roy Choudhury
Genes and Therapy
Managing Editor
Nisha Peter, PhD
Managing Editor
Abhi Dey
Consulting Editor
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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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