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MedNess: bite-size biopharma and medtech news

21st October, 2020
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Onco I-Analyse
Agios withdrew Ivosidenib’s MAA in R/R AML
On 16th October, Agios Therapeutics announced that it has withdrawn the Marketing Authorization Application (MAA) for Ivosidenib (Tibsovo) filed with the European regulatory bodies based on the feedback from the EMA’s Committee for Medicinal Products for Human Use (CHMP). Company had filed Ivosidenib for the treatment of adults with relapsed or refractory (R/R) AML with an IDH1 mutation.
CHMP had communicated that the clinical data from Phase I single-arm, uncontrolled study is insufficient to show favorable benefit-risk ratio and subsequently support approval. Currently, there are no approved therapies in Europe for AML patients with IDH-1 mutation.
However, the FDA approved Ivosidenib for R/R AML with IDH1 mutation in June 2018 based on the same Phase I study which demonstrated a CR+CRh of 32.8%, mDOR of 8.2 months. 37.3% patients became RBC and platelet transfusions independent during any 56-day post-baseline period
In December 2019, Celgene/BMS had also withdrawn its MAA for enasidenib (Idhifa) for R/R AML with IDH-2 mutation as it failed to justify the benefit-risk profile. At that time, Agios had argued that IDH-1m+ AML had poorer prognosis than IDH-2m+ AML and conducting a large-scale randomized trial was not feasible in R/R settings.
Additionally, in May 2019, Ivosidenib was FDA approved in 1L AML patients with IDH1 mutation who are either ≥75 years old or have co-morbidities and cannot tolerate intensive chemotherapy.
While, Agios does not have an ongoing Phase III trial in R/R AML, it does have two Phase III, randomized, placebo-controlled studies ongoing in frontline AML patients with IDH-1 mutation. The first trial (AGILE) assesses Ivosidenib in combination with azacitidine in patients ineligible for intensive chemotherapy. The second trial (HOVON150AML), evaluates Ivosidenib in combination with standard induction, consolidation and maintenance therapy in patients eligible for intensive chemotherapy. Agios plans to file for approval with US and EU regulatory authorities, if the results from these Phase III studies are positive.
Collated by :Shilpa Rawal, PhD
COVID Special
Johnson and Johnson temporarily pause all dosings of their COVID-19 vaccine candidate from Janssen 
Following their recent announcement of initiating the Phase 3 clinical trial for Janssen’s COVID-19 vaccine, Johnson and Johnson recently announced that they have paused the dosing in all their COVID-19 vaccine trials, including the ENSEMBLE, Phase 3 trial. The decision was taken based on an unexplained illness experienced by one of the study participants. The unexplained illness will be looked into by the internal clinical safety physicians and will also be evaluated by the independent Data Safety Monitoring Board (DSMB) of ENSEMBLE. Serious adverse effects of illness in general may occur and is an expected part of a clinical trial. Further investigation is underway to determine the cause of this adverse effect and also to understand if it is vaccine related since it is not always immediately evident if the patient was on a placebo or on the study treatment.
Long-acting antibody combination of AstraZeneca progresses to the Phase III clinical trial phase
AstraZeneca’s long-acting antibody combination, AZD7442 proceeds to two Phase III clinical trials. These trials will include more than 6000 individuals and will occur globally. The trials are estimated to begin very soon. AstraZeneca has received $486 million in support from the US government based on their agreement with BARDA and the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense. This financial support is above and beyond the previous funding of $25 million that the US government agencies had offered to evaluate monoclonal antibodies as well as determine the safety and tolerability of AZD7442 in healthy individuals in the Phase I clinical trials that started in August 2020.
“This agreement with the US Government will help accelerate the development of our long-acting antibody combination which has the potential to provide immediate and long-lasting effect in both preventing and treating COVID-19 infections. We will be evaluating the LAAB combination in different settings from prophylaxis, to outpatient treatment to hospitalization, with a focus on helping the most vulnerable people.”, said Pascal Soriot, Chief Executive Officer.
Click here for more COVID news
Collated by : Esha Sehanobish, PhD
Drug Approvals
VENCLEXTA® (venetoclax) Receives FDA Full Approval for 1L AML patients ineligible for intensive chemotherapy
"AML is a complex and challenging disease with generally low survival rates. This approval is significant because data from our VIALE-A trial has shown that newly-diagnosed patients, who cannot undergo intensive chemotherapy, lived longer when treated with VENCLEXTA plus azacitidine than those treated with azacitidine alone," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology development, AbbVie. "This trial also provides physicians more information for managing patients - from treatment initiation, to assessing response and management post disease remission."
KEYTRUDA® (pembrolizumab) gets FDA approval in Adult R/R cHL Patients
“The patients with cHL who do not achieve remission following initial treatment or who relapse after transplantation face a poor prognosis, reflecting the unmet need for improved therapies in the relapsed/refractory setting,” said Dr. John Kuruvilla, hematologist and associate professor of medicine, Princess Margaret Cancer Centre and University of Toronto. “With this approval, KEYTRUDA has the potential to change the current standard of care and help these patients achieve better outcomes.”
Regulatory News
FDA Accepts for Priority Review Applications for OPDIVO® (nivolumab) + CABOMETYX® (cabozantinib) in Advanced RCC
“With their complementary mechanisms of action and evidence that CABOMETYX may promote a more immune-permissive environment, we believe there is opportunity for additive or synergistic effects with this potential combination regimen,” said Gisela Schwab, M.D., president, product development and medical affairs and chief medical officer, Exelixis. “Based on strong supporting data from CheckMate -9ER, the acceptance of our application is important progress in our efforts to make CABOMETYX in combination with OPDIVO available to patients with advanced kidney cancer who need additional treatment options. We look forward to working with the FDA throughout the ongoing review process.”
European CHMP Adopts Positive Opinion for KTE-X19 for the Treatment of R/R MCL
“This opinion is an important milestone for patients in Europe living with relapsed or refractory mantle cell lymphoma,” said Ken Takeshita, MD, Kite’s Global Head of Clinical Development. “Kite is committed to bringing the promise of CAR T cell therapy to patients with hematological cancers and, pending approval by European Commission, we hope to bring this innovative treatment option forward for patients in Europe as quickly as possible.”
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Trial Results and Statuses
FAILED TRIAL: Ph 3 ASTRAL-2 and ASTRAL-3 studies of guadecitabine (SGI-110) in patients with previously treated AML and MDS/CMML did not meet the primary endpoint of statistically significant OS improvement
“We are disappointed in the outcome of the ASTRAL-2 and ASTRAL-3 studies,” said Mohammad Azab, Astex’s president and chief medical officer.  “The ASTRAL series of studies were designed to deliver a new therapeutic option to patients with AML or MDS/CMML, and although guadecitabine is an active drug, the studies failed to demonstrate a statistically superior survival outcome compared to current therapeutic alternatives.” Dr. Azab also added, “The ASTRAL studies generated for the medical community one of the largest bodies of clinical and genetic data from prospective randomized studies using hypomethylating agent (HMA) treatment. Guadecitabine was associated with improved outcomes in certain subgroups, but that needs to be validated by additional studies. We are extremely grateful to all the patients, physicians and other healthcare professionals, and collaborating research and manufacturing organizations who contributed to this global effort.”
Aliqopa™ (copanlisib) + Rituximab Ph 3 CHRONOS-3 trial Meets Primary Endpoint in Relapsed iNHL Patients
“Indolent forms of Non-Hodgkin’s Lymphoma are a heterogenous group of malignancies characterized by a chronic pattern of remissions and recurrences. For iNHL patients with disease progression who are in need of treatment, there are few approved treatment options,” said Dr. Scott Z. Fields, Senior Vice President and Head of Oncology Development at Bayer. “The positive results from CHRONOS-3 demonstrate the potential clinical benefit of copanlisib in combination with rituximab, to address the unmet medical need in these patients.”
Click here for more Trial Results and Statuses
Collated by : Richa Tewari, PhD
Medness Plus
FDA approves the first treatment for Ebola virus in the form of a mixture of antibodies
FDA recently approved a mixture of three structurally similar monoclonal antibodies, Inmazeb (atoltivimab, maftivimab, and odesivimab-ebgn) for the treatment of Ebola virus (Zaire ebolavirus). This is the first FDA-approved treatment for the virus and aims to treat both pediatric and adult patients. The drug received an Orphan drug designation and a Breakthrough Therapy designation. The orphan drug designation will provide incentive to encourage and aid the development of treatments for rare diseases. The approval for the antibody cocktail was given to Regeneron. This is the first antibody treatment available for Ebola after the vaccine, Ervebo was approved in December 2019.
“We are incredibly proud that the FDA has approved Inmazeb, which is also known as REGN-EB3. This is the first time the FDA has approved a treatment specifically for Ebola, which has caused a number of deadly outbreaks,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron.
Dupixent reduces severe asthma attacks in children and shows improvements in children’s lung function
Results from a recent pivotal Phase 3 trial in children 6-11 years and with uncontrolled moderate-to-severe asthma, showed that Dupixent was able to meet all its key primary and secondary endpoints.
Dupixent when added to the standard of care was also able to significantly reduce asthma exacerbations and improve lung functions after the first dose itself in patients with eosinophilia or increased elevated levels fractional nitric oxide (FeNO). Majority of the children in the study had at a minimum, one type 2 concurrent inflammatory conditions. The safety profile was similar to that of the patients on Dupixent who were 12 years and older with moderate-to-severe asthma.
“Children with uncontrolled moderate-to-severe asthma often struggle to breathe, largely because of their impaired lung function, and this can have a serious impact on their quality of life. It not only reduces their ability to participate in day-to-day activities,but can also take a huge emotional toll on the child and their family,” said John Reed, M.D., Ph.D., Global Head of Research and Development at Sanofi.
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Collated by : Esha Sehanobish, PhD
Medness Reviews

FDA approves Inmazeb as the first treatment for Ebola virus 
REGN-EB3 (INMAZEB®), developed by Regeneron has recently received FDA approval for the treatment of Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients. Inmazeb is a mixture of three monoclonal antibodies (atoltivimab, maftivimab, and odesivimab) that targets multiple, non-overlapping epitopes of the Ebola virus glycoprotein. Glycoprotein attached to the cell receptor modulate the entry of the virus into the human body. This antibody mix blocks the viral attachment and prevents the entry of the virus into the human body.
Inmazeb was tested in a clinical trial named PALM trial in 2018 and 2019 during an outbreak of Ebola in the Democratic Republic of the Congo. The randomized and controlled PALM trial reported that after 28 days of Inmazeb administration caused 33.8% death from 154 patients while 51% of the 153 patients died who received a control.
The most common side effects of Inmazeb were pyrexia (or elevation in fever), chills, tachycardia, tachypnea, vomiting, hypotension, diarrhea, and hypoxia. Concurrent administration of a live vaccine during treatment with Inmazeb should be avoided as it might inhibit the replication of the live virus and potentially reduce the efficacy of the vaccine.
"Today's approval highlights the importance of international collaboration in the fight against Ebola virus," said John Farley, director of the Office of Infectious Diseases in the FDA's Center for Drug Evaluation and Research.
Collated by :  Rinki Saha 
Medness Business
Onco-News

Boehringer Ingelheim and Oxford BioTherapeutics Expand Collaboration to Discover Novel Selective Tumor Targets as First Bispecific Antibody Advanced into the Clinic
“This collaboration with Oxford BioTherapeutics is important for advancing therapeutic modalities that depend upon the identification of unique and specific tumor antigens within our cancer immunology portfolio,” said Jonathon Sedgwick, Ph.D., Senior Vice President and Global Head Cancer Immunology & Immune Modulation Research at Boehringer Ingelheim. “We are committed to developing innovative, efficacious and safe treatment options for patients suffering from cancer, and these novel cancer target discoveries are a key step in the development of new potential treatments.”
ImmunityBio, Inc. and NantKwest, Inc. to add CytRx’s licensed drug aldoxorubicin to a third cohort to Ph 2 QUILT-88 study of Anktiva (N803) + t-haNK for locally advanced or metastatic pancreatic cancer
“Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States and requires significant advancements in treatment to improve outcomes for patients,” said Steven A. Kriegsman, CytRx’s Chairman and Chief Executive Officer. “We commend the Companies for adding a third cohort and expanding this Phase 2 study of their combination immunotherapy that includes aldoxorubicin. We are encouraged that aldoxorubicin continues to play a role in their mission to recruit and amplify the power of the human body’s own immune system to target and destroy even the most difficult cancer cells.”
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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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