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MedNess: bite-size biopharma and medtech news

2nd December, 2020
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HIGHLIGHTS
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Onco-I-Analyse
The US FDA granted accelerated approval to Y-mAbs’ DANYELZA® (naxitamab-gqgk) for the treatment of Neuroblastoma 
On November 25, Y-mabs announced that the US FDA has granted accelerated approval to Danyelza (naxitamab-gqgk), in combination with GM-CSF, for the treatment of relapsed or refractory high-risk neuroblastoma in the bone or bone marrow. The approval is granted for pediatric (1 year of age and older) and adult patients with partial response, minor response, or stable disease to prior treatment.
The approval was based on ORR and duration of response (DoR) data from two pivotal studies - Study 201 and Study 12-230. Study 201 evaluated 22 patients and demonstrated an ORR of 45%. 30% of responders showed DoR of ≥6 months. Study 12-230 evaluated 38 patients showing an ORR of 34%. 23% of patients showed DoR of ≥6 months
The FDA has added a black box warning of “Serious Infusion-related reactions and neurotoxicity” on the Danyelza label which can affect utilization. However, Danyelza was generally well-tolerated with few discontinuations and clinically manageable AEs.
The continued approval is contingent upon clinical benefits seen in confirmatory trials. Study 201 plans to enroll 80 patients, evaluate ORR as the primary endpoint, DoR as secondary endpoint and PFS and OS as secondary endpoints in long-term follow up. Y-mabs will also initiate a Phase III study of Danyelza in combination with GM-CSF and chemotherapy in pediatric and adults patients with high-risk neuroblastoma and primary refractory disease or in first relapse.
Y-mabs also has another humanized bispecific anti-GD2 antibody, Nivatrotamab, in Phase I evaluation in patients with relapsed/refractory neuroblastoma, high grade osteosarcoma and GD2+ solid tumors. The drug was granted Orphan Drug Designation and Rare Pediatric Disease Designation by the US FDA
Danyelza is expected to be available in the US in coming weeks.
Neuroblastoma is the most common extracranial solid tumor in childhood with >650 cases diagnosed each year in the US. Danyelza had earlier received Priority Review, Breakthrough Therapy Designation, and Rare Pediatric Disease designation from the FDA for neuroblastoma.
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COVID Special
AstraZeneca in collaboration with the University of Oxford announce positive results for their candidate COVID-19 vaccine 
AstraZeneca announces positive results from the interim analysis of the COVID-19 vaccine AZD 1222 that they have developed in collaboration with the Oxford University. The results were from clinical trials that are currently being conducted in the UK and Brazil. Based on the interim analysis conducted on a total of 131 COVID-19 cases, the vaccine was able to reach the primary endpoint that is prevention of COVID-19 with no hospitalization or severe cases related to COVID-19 among those who were vaccinated. The interim analysis was performed by an independent data safety monitoring board. The company aims to manufacture up to 3 billion doses of the vaccine in 2021 post-approval and on a rolling basis. The vaccine can be stored and transported in 2-8 degree Celsius for at least six months and can be administered in a clinical setting.
Professor Andrew Pollard, Chief Investigator of the Oxford Vaccine Trial at Oxford said, “These findings show that we have an effective vaccine that will save many lives. Excitingly, we’ve found that one of our dosing regimens may be around 90% effective and it this dosing regime is used, more people could be vaccinated with planned vaccine supply. Today’s announcement is only thanks to the many volunteers in our trial, and the hard working and talented team of researchers around the world.”
FDA issued an Emergency Use Authorization for baricitinib in combination with remdesivir for the treatment of COVID-19
FDA recently issued an EUA for the combination use of baricitinib with remdesivir for the treatment of suspected and laboratory confirmed COVID-19 hospitalization in adult patients and those two years and older requiring extracorporeal membrane oxygenation (ECMO), invasive mechanical ventilation or supplemental oxygen. The EUA was granted to Eli Lilly. The use of the combination treatment under the EUA will only be authorized for the duration of the declaration that circumstances exist that justify the authorization of the emergency use unless the authorization is revoked or terminated sooner. Based on the EUA, the fact sheets with information on the usage of the combination drugs must be made available to COVID-19 patients and to healthcare providers and care givers. The fact sheets contain information about doses, potential side effects and drug interferences and interactions.
“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, M.D. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
Click here for more COVID news
Collated by : Esha Sehanobish, PhD
Drug Approvals
EU Approves Opdivo (nivolumab) as 2L Treatment for Unresectable Advanced, Recurrent or mESCC
“Today’s approval marks a critically important milestone for those living with esophageal squamous cell carcinoma, as this is the first time an immunotherapy treatment option has been approved in the European Union for this patient population,” said Ian M. Waxman, M.D., development lead, gastrointestinal cancers, Bristol Myers Squibb. “We are proud of our work in advancing treatment options for people living with upper gastrointestinal cancers, and we look forward to working with European stakeholders to bring Opdivo to more eligible patients who may benefit.”
MHLW approves CABOMETYX® (cabozantinib) for the treatment of unresectable, previously treated HCC in Japan based on Ph 3 CELESTIAL (XL184-309) and Ph 2 Cabozantinib-2003 trials data
“Hepatocellular carcinoma causes approximately 30,000 deaths in Japan each year and is a leading cause of cancer-related death worldwide,” said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. “The approval of CABOMETYX in Japan is an exciting next step toward bringing this treatment to liver cancer patients who otherwise have limited treatment options following prior systemic therapy. We’re proud to collaborate with Takeda as we work to bring this treatment to patients in Japan.”
Regulatory News
FDA grants Fast Track Designation for Eprenetapopt in the Treatment of TP53 Mutant AML
“We are pleased to have received Fast Track designation for eprenetapopt in the treatment of TP53 mutant AML, a cancer for which outcomes are poor and there are no current therapeutic options specifically for these patients,” said Eyal C. Attar, M.D., Chief Medical Officer of Aprea. “Emerging data from our AML trials evaluating eprenetapopt with azacitidine, and with eprenetapopt, azacitidine and venetoclax, are promising and we continue to enroll patients to identify the best treatment regimen. As these data mature in 2021, we look forward to continued interaction with FDA as we map out opportunities for an accelerated pathway to potential approval.”
FDA grants Breakthrough Therapy Designation to Zanidatamab in Biliary Tract Cancer Patients
“This Breakthrough Therapy designation from the FDA, based on data generated in BTC patients treated in the initial Phase 1 trial, is recognition of the potential of zanidatamab to provide a new approach to cancer treatment,” said Diana Hausman, M.D., Chief Medical Officer at Zymeworks. “This milestone supports our strategy for accelerated approval and will help make zanidatamab available for patients as quickly as possible.”
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Trial Results
Ph 3 SIENDO Study of XPOVIO® (Selinexor) in Endometrial Cancer Patients Passes Planned Interim Futility Analysis: DSMB Recommends the Study Should Proceed as Planned Without Any Modifications
"We are very excited that the SIENDO study has passed its planned futility analysis and that the study will continue as planned," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We believe this is an encouraging development for the study, and more importantly, for patients and families in need of novel treatment options for advanced or recurrent endometrial cancer. There are currently no approved therapies in the maintenance setting for patients with advanced endometrial cancer, making the future trial results from the SIENDO study, particularly important. We expect to report top-line data from this study in the second half of 2021."
Positive Data from Ph 2 CAPTIVE (KEYNOTE-192) Study with DNX-2401 in rGBM Patients announced
“We are excited by the promising activity seen in patients with recurrent GBM, which is a notoriously difficult-to-treat cancer with a high mortality rate,” said Jeffrey Knapp, chief executive officer of DNAtrix. “The median overall survival of 12.5 months achieved with DNX-2401 and pembrolizumab compares very favorably against historical benchmarks for standard of care agents, lomustine and temozolomide, where our meta-analysis indicates the median overall survival achieved with either of these therapies is on the order of 7.2 months. We look forward to advancing this treatment regimen into a global, randomized Phase 3 study. Additionally, we are also evaluating DNX-2401 in a Phase 1 study for the treatment of diffuse intrinsic pontine glioma, where we have received FDA Fast Track and Rare Pediatric Disease designations. Beyond DNX-2401, we are poised to begin a Phase 1 study in patients with colorectal and other cancers with liver metastases with our second product candidate, DNX-2440, an armed oncolytic virus that induces the expression of OX40 ligand on tumor cells.”
Click here for more Trial Results
Trial/Program Status
Enapotamab vedotin program to be shelved
“We are committed to developing innovative antibody products for patients with cancer, however the data from the enapotamab vedotin expansion cohorts unfortunately does not support moving this product candidate forward. This decision will allow us to focus more of our resources and energy on other programs in our robust next-generation antibody therapeutics pipeline,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
First Patient Dosed in Ph 2 LUMINOS-101 Trial of PVSRIPO + Pembrolizumab for rGBM Patients
“The initiation of this Phase 2 trial represents a significant milestone in the advancement of PVSRIPO and our quest to treat this formidable opponent,” said Matt Stober, President and Chief Executive Officer at Istari Oncology. “Currently the treatment options for patients with rGBM are limited and outcomes are grim, so following the encouraging results of our Phase 1 trial, we are eager to see the effectiveness of PVSRIPO in combination with pembrolizumab.”
Click here for more Trial Status
Collated by : Richa Tewari, PhD
Medness Plus
FDA expands the use of Xofluza to include post-exposure prevention of influenza
FDA expanded the approved indication for Xofluza (baloxavir marboxil) to include post-exposure prevention of influenza. The approval is indicated for patients 12 years and older who have come directly in contact with an individual infected with flu. Xofluza’s prior approval in 2018 was for the treatment of uncomplicated flu in patients 12 years and older who have not been symptomatic for more than 48 hours. It was initially available only as tablets. But currently, it is also available as granules that can be mixed with water. The expansion of the approval was granted to Genentech USA, Inc.
“This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic,” said Debra Birnkrant, M.D., director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research. “Americans will have to be more vigilant than ever as these viruses spread concurrently.” “With today’s approval, Xofluza is now available as the first single-dose, post-exposure preventive treatment for influenza,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We’re hopeful that reducing the burden of influenza may help to mitigate the strain on our healthcare system amid the COVID-19 pandemic.”
Click here for more MedNess Plus
Collated by : Esha Sehanobish, PhD
Medness Reviews

*Data compiled from public source as of 29th November 2020
The COVID-19 Vaccine Race – The technology behind Pfizer and Moderna’s Vaccine and AstraZeneca’s Trial Results
The recent release of the interim analyses results of both Pfizer/BioNTech’s and Moderna’s COVID-19 vaccine candidates has spurred optimism of probably having an effective vaccine on the market very soon. Both vaccines use mRNA technology and differ from traditional vaccines technologies previously approved for clinical use for other infectious diseases. Either or both vaccine candidates if approved by FDA, will be the first of its kind vaccine approved for the treatment of COVID-19. Let’s take look into the technology behind both vaccines and see how they compare.

The mRNA Vaccine Technology
Traditional vaccines contain either weakened viruses or purified signature proteins of the virus to evoke an immune response. In mRNA vaccines, the mRNA that encodes the viral protein is injected instead of the protein. The intramuscularly injected mRNAs are then translated by muscle cells to make the viral proteins directly in the body. This gives the immune system a preview of the virus to design powerful antibodies that can neutralize the virus albeit without causing the disease. After injection, the mRNA guides the protein production inside muscle cells , which reaches peak levels or 24 to 48 hours and can last for a few more days.
The mRNA vaccine development is faster than traditional vaccine development and has thus far shown to be able to respond quickly against novel pandemics like COVID-19. This is because mRNAs can be synthesized chemically and can circumvent the longer time and onerous process needed for the development of weakened viruses or production of viral proteins at medically demanding levels of purity.
Although mRNA vaccine technology has been around for a while, it earlier faced some problems due to the notoriously unstable nature of mRNA and destruction of mRNA by the human body’s immune responses without an efficient delivery method. However, in the beginning of 2005, researchers figured out how to stabilize mRNA and also package into small vehicles to deliver as a vaccine.
Currently, the instability of mRNA above freezing temperatures is still most important challenge for development of an mRNA, vaccine making this new class of vaccine require freezer conditions for distribution and administration.

How do the Vaccines Compare?
Moderna reported that during the phase 3 study of its vaccine candidate mRNA-1273, which enrolled 30,000 adult U.S. participants, just five of the 95 COVID-19 cases occurred among the vaccinated, while 90 infections were identified in the placebo group. This corresponds to an efficacy of 94.5%. None of the infected patients who received the vaccine developed severe COVID-19, while 11 (12%) of those who received the placebo did. The company plans to submit the results of the study to the regulatory authorities.
Similarly, the Pfizer-BioNTech reported that in phase 3 clinical trial of its vaccine candidate BNT162b2, which enrolled 43,661 participants to date, 41,135 of whom have received a second dose of the vaccine candidate, just 8 of the 170 COVID-19 cases occurred among the vaccinated cases, while 162 infections were identified in the placebo group. This corresponds to an efficacy of 95%. Additionally, the observed efficacy in adults over 65 years of age was over 94%. On Friday, Pfizer has submitted an application for the emergency use authorization of the vaccine to the FDA and the result is anticipated on December 10,2020.
Both analyses counted the number of participants who contracted the virus following two shots of placebo or vaccine. However, Moderna’s interim analyses counted participants 14 days following the second injection, whereas Pfizer started counting after seven days of the second injection. To be considered as COVID positive, Moderna required the participant to have at least two symptoms of disease in addition to a positive test for the virus. The Pfizer study required only one symptom in addition to a positive test
In terms of safety, both companies reported mild to moderate side effects such as fatigue, muscle pain and headaches with no serious side effects for their respective vaccine candidates. 
The major difference between the Moderna and Pfizer vaccine candidates however is their storage temperature and shelf life. The Pfizer-BioNTech mRNA vaccine will need to be optimally stored at minus 94 degrees Fahrenheit and will degrade in around five days at normal refrigeration temperatures of slightly above freezing. This might make the distribution of vaccine difficult.
In contrast, Moderna says that its vaccine can be maintained at most home or medical freezer temperatures for up to six months for shipping and longer-term storage. Moderna also claims its vaccine can remain stable at standard refrigerated conditions, of 36 to 46 degrees Fahrenheit, for up to 30 days after thawing, within the six-month shelf life.

AstraZeneca Releases Preliminary Data on its Trials
Shortly after the release of the results by Pfizer and Moderna, British drugmaker AstraZeneca also released the preliminary results for its coronavirus vaccine candidate. The company announced that their vaccine candidate AZD1222, which is based on adenovirus vaccine technology, was 62% and 90% effective, depending on the level of dose given and the overall efficacy was reported to be 70%. The trials had followed two different dosing regimens – the first used two regular doses and reached 62% efficacy. The second had a lower dose, followed by a regular dose, with an efficacy of 90%. However, several experts have raised questions on how the data was collected and presented, and why two different dosing regimens were used.
AstraZeneca provided details attributing change in dosing intensity to the scale up of the amount of vaccines for the trial. While the public awaits the release of the full data and the peer-reviewed analysis of the trial, AstraZeneca plans to further investigate the half-dose/full-dose regimen.
While compared to Moderna and Pfizer’s vaccine candidate, the vaccine technology used by AstraZeneca has been previously approved regulatory agencies for the treatment of Ebola and would be cheaper and easier to scale up for production and distribution
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Medness @ HealthIT
Machine learning makes COVID19 diagnosis more accurate from chest X-ray
The rampaging pandemic has made some of the resources scarcely available while the expert physicians have been stretched thin. What if machine learning could execute the diagnosis of COVID19 from an inexpensive chest X-ray image instead of a radiologist assessing the report to distinguish COVID9 cases from pneumonia, heart failure, chronic lung illnesses or other less-infectious diseases? One of the characteristics finding of a COVID-lung is These ‘bilateral consolidations.’ where lungs are filled with fluid and inflamed, mostly along the lower lobes and periphery. In a recent study, researchers have used 17,002 chest x-rays to develop, train, and test a machine learning algorithm, which was then able to read the COVID cases 10 times faster. While the accuracy for physicians ranged from 79-81%, the ML algorithm consistently provided an 82% accuracy. However, given the fact that not all COVID cases exhibit with lung complications, especially in the early stages, the algorithm will not be able to replace the standardized testing for COVID.
AI-application to combat Parkinson’s disease
Artificial intelligence finds an avenue to offer solutions in the diagnosis of Parkinson’s disease by collecting and measuring data from the speech patterns of the existing patients. It is a disease with heterogeneous effects on motor and non-motor symptoms, including speech pattern. The disease currently affects around 10 million people around the globe. The research is conducted by a team in Purdue university, which looks towards leveraging telehealth to collect data from patients, while the pandemic continues to make people more conversant with telehealth-features. According to Andrew Exner, a graduate research assistant in the Motor Speech Lab, the research will bring about a “standardization in assessments, earlier diagnoses and possibly an easier way to track discrete changes over time to guide interventions.” An earlier collaboration of IBM with Michael J. Fox Foundation also sought to develop a machine learning algorithm using data from patients on medications.
Medness Business
Onco-News
Telix Pharmaceuticals Limited Acquires TheraPharm GmbH
  • Telix Pharmaceuticals entered an agreement with Scintec Diagnostics GmbH to acquire TheraPharm GmbH.
  • TheraPharm GmbH develops innovative diagnostic and therapeutic solutions in the field of hematology.
  • TheraPharm is developing antibody MTR technology against CD66 for broad applications in the diagnosis and treatment of blood cancers, infection management and other lymphoproliferative diseases.
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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