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MedNess: bite-size biopharma and medtech news

28th July, 2021
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MedNess This Week
HIGHLIGHTS
Onco-I-Analyse
Venetoclax + Azacitidine combination receives Breakthrough Therapy Designation for 1L, higher risk MDS
On 21st July, Roche and AbbVie that venetoclax (Venclexta/Venclyxto), the Bcl-2 inhibitor co-development by both companies, has been granted breakthrough therapy designation (BTD) by the US FDA in combination with azacitidine as a frontline treatment option for intermediate-, high- and very high-risk myelodysplastic syndromes (MDS) as per the revised International Prognostic Scoring System (IPSS-R). The designation is based on initial data from the Phase 1b M15-531 study.
Background: MDS are a rare, heterogenous group of hematological cancers affecting hematopoiesis at the stem cell level. High risk MDS has a median survival of 18 month and ~30% patients progress to AML, every year. The management of MDS is complex due to the older median age of diagnosis (70-75 years) and lower quality of life (QoL) for these patients.
Hypomethylating agents (azacitidine, decitabine) are considered the standard treatment for higher risk patients, ineligible for Allo-HSCT but demonstrated lower ORR and mOS.
Details: The Phase 1b, single group assignment trial is evaluating venetoclax + azacitidine in 137 treatment-naïve patients with intermediate, high or very high MDS. Interim analysis presented during ASH 2020 included data from 57 patients. At a median follow-up of 13 months, the ORR was 77% (CR: 42%, marrow CRs: 35%) and mDOR was 14.8 months. Of the patients with CR, 40% showed CR with hematological improvement. Although the mOS was not reached, mPFS was 17.5 months.
97% patients experienced Grade ≥3 AEs and the 30-day mortality was 2%. The combination did show improvements in the QoL of patients.
Implications: Venetoclax is also being studied in two additional trials – Phase 1b M15-522 (± azacitidine in R/R MDS) and a confirmatory Phase 3 VERONA (+ azacitidine in newly diagnosed higher-risk MDS) to address a broader patient population. It has earlier received 5 more BTDs in hematological cancer and is also approved for various AML and CLL/SLL patient segments, highlighting its potential as a promising treatment option.
Collated by: Shilpa Rawal, PhD
Drug Approvals
FDA Approves KEYTRUDA® Plus LENVIMA® Combination for Patients With Certain Types of Advanced Endometrial Carcinoma
“With a five-year survival rate of just 17%, women with advanced endometrial cancer who are not candidates for curative therapy, particularly those with disease progression following prior systemic therapy, have limited treatment options,” said Dr. Vicky Makker, principal investigator and medical oncologist, Memorial Sloan Kettering Cancer Center. “This approval is an important step forward in helping patients fight this difficult-to-treat malignancy, as physicians can now provide an option that may improve survival outcomes.”
Regulatory News

FDA’s clinical hold letter related to IND to initiate Ph 1/2 trial of MGTA-117 in AML/MDS patients
 “We are actively developing the bioassay requested by the FDA and do not expect significant technical challenges in its completion. We expect to request a ‘Type A’ meeting in the coming weeks and, if successful in resolving this remaining issue, we would anticipate opening the study in Q4 2021,” said Jason Gardner, D.Phil., President and Chief Executive Officer, Magenta Therapeutics. “We are greatly appreciative of the FDA’s continued engagement as we seek to commence the Phase 1/2 clinical trial of MGTA-117 and develop this potentially first-in-class medicine to improve conditioning options for patients across a number of disease areas.” 
FDA granted Fast Track designation to COSELA™ (trilaciclib) + chemotherapy for the treatment of locally advanced or mTNBC
“Fast Track designation underscores the urgent need for innovative drugs that can significantly improve TNBC patient outcomes,” said Raj Malik, M.D., Chief Medical Officer at G1 Therapeutics. “It provides an important pathway to help expedite the development and regulatory review of COSELA in this indication. We look forward to working closely with the FDA as we advance this pivotal program in TNBC and continue to work to unlock the broader potential of this pipeline-in-a-molecule compound that we hope will help patients across multiple tumor types.”
Click here for more Regulatory News
Trial Results
Preliminary Results Announced from 30 mTNBC Patients Treated with Leronlimab
Daniel Adams, Director of Clinical Research & Development, Creatv MicroTech, Inc., stated, “While these are only interim results at the 12-month point, our ability to rapidly monitor and identify patients that appear to respond to leronlimab using a single tube of blood is quite an encouraging finding. The fact that greater than 70% of patients saw positive changes in circulating tumor cells after a single dose of leronlimab was made even more informative by their dramatic increases in both progression-free survival and overall survival. The fact that a large group of patients taking leronlimab had an mPFS of approximately 6 months is well beyond that experienced with current treatment options available to these women, who typically have mPFS of approximately 2 months. This result is even more amazing as these women did not even reach mOS in 12 months, considering the typical mOS in this population is only 6 to 7 months.”
Positive Results Announced from Ph 2 Trial of Eprenetapopt + Azacitidine for Post-Transplant Maintenance Therapy in TP53 Mutant MDS and AML
“The post-transplant RFS and OS data with eprenetapopt and azacitidine maintenance therapy in these very difficult-to-treat TP53 mutant MDS and AML patients are incredibly exciting,” said trial principal investigator Asmita Mishra, M.D., of the H. Lee Moffitt Cancer Center and Research Institute. “Although transplant is currently the only potentially curative treatment for patients with TP53 mutant MDS and AML, the risk of relapse with current standard of care remains unacceptably high and the median OS post-transplant is very limited at 8 months or less. Post-transplant maintenance therapy with eprenetapopt and azacitidine could, if approved, represent a new treatment paradigm that meaningfully improves outcomes for these patients with limited treatment options.”
Trial/Program Status
DSMB recommends to Continue Dosing Patients in the Ph 2 Portion of the OVATION 2 Study with GEN-1 in Advanced Ovarian Cancer
“These findings show a consistent dose-dependent clinical response in both surgical outcome and tumor response, which is further supported by translational data of the tumor microenvironment,” noted Nicholas Borys, M.D., Celsion’s executive vice president and chief medical officer. “Continuing our clinical research program at the 100 mg/m2 dose in patients with advanced-stage ovarian cancer holds promise and is strongly encouraged by our study investigators and medical advisors.”
FDA gives go-ahead to plan to submit an intermediate size expanded access protocol for use of OKN-007 in patients with high-grade gliomas
Regarding the iEAP, an official from the Company stated that “After we released the news regarding the development of our new DIPG treatment, several DIPG patient families reached out to the Company asking to participate in the clinical trial. Since DIPG and other gliomas progress rapidly, Oblato wanted to make the treatment available as quickly as possible and to as many of these patients as possible. The Company decided to use the iEAP first to give an opportunity for patients with either DIPG or high-grade gliomas for which there is either no effective treatment or they are ineligible to participate in a clinical trial. Using the iEAP, Oblato can administer our investigational medicinal product even before we initiate the clinical trial. Currently, we are in discussion with a firm experienced with the iEAP and plan to submit the protocol for the iEAP to the FDA as soon as possible.”
     Click here for more Trial/Program Statuses
MedNess Business
Onco-News
Arvinas and Pfizer Announce Global Collaboration to Develop and Commercialize PROTAC® Protein Degrader ARV-471
“This collaboration has the potential to be transformational, as it combines our leadership in targeted protein degradation with Pfizer’s global capabilities and deep expertise in breast cancer. This should significantly enhance and accelerate the development and potential commercialization of ARV-471 while also advancing Arvinas’ strategy of building a global, integrated biopharmaceutical company,” said John Houston, Ph.D., Chief Executive Officer at Arvinas. “We share Pfizer’s deep commitment to people with breast cancer and are thrilled to partner with them to develop this potentially best-in-class therapy. Despite advancements in oncology in recent years, considerable unmet need persists in the treatment of HR+ breast cancer. Together with Pfizer, we will deploy our PROTAC technology in an effort to help people with this devastating disease.”
Adagene and Merck to Advance Two Anti-CTLA-4 Monoclonal Antibody Programs (ADG116 and ADG126) in Combination with KEYTRUDA
“This collaboration with Merck and the advancement of our global clinical studies represent an important milestone in our comprehensive CTLA-4 clinical development program,” said Peter Luo, Ph.D., Co-founder, Chief Executive Officer and Chairman of Adagene. “Our AI-driven platforms have generated two highly differentiated CTLA-4 targeting molecules, ADG116 and ADG126. ADG116, our NEObody™ CTLA-4 candidate, is designed with strong antibody-dependent cellular cytotoxicity (ADCC) and softened T cell activation which combined, leading to increased potency with an improved safety profile. Our SAFEbody™ candidate ADG126 effectively limits on-target off-tumor toxicities in normal tissues and is designed for a superior systemic safety profile at efficacious dose levels with a significantly enhanced therapeutic window to overcome existing issues associated with current anti-CTLA-4 therapies.”
Click here for more on mergers, acquisition and business news
Collated by: Richa Tewari, PhD
Editors' Desk
Richa Tewari, PhD
Oncology News
Shilpa Rawal, PhD
Onco I-Analyse
Arundithi Ananthanarayanan
MedNess Reviews
Divyaanka Iyer
BioPharma News
Debarati Banik
HealthIT
Darpan Chakraborty
Social Media Manager
Nisha Peter, PhD
Consulting Editor
Abhi Dey
Consulting Editor
Rinki Saha
BioPharma News
Managing Editor
Shalini Roy Choudhury
Genes and Therapy
Managing 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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