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MedNess: bite-size biopharma and medtech news

31st March, 2021
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MedNess This Week
HIGHLIGHTS
Onco-I-Analyse
BMS’ and Bluebird Bio’s Abecma becomes the first anti-BCMA CAR-T to get FDA nod for R/R MM
On 26th March, BMS and bluebird bio announced that idecabtagene vicleucel (Abecma), BCMA-targeting CAR-T cell therapy, received FDA approval for patients with relapsed or refractory multiple myeloma (RRMM) progressing after at least four prior lines of therapies. Prior therapies included standards of care - proteosome inhibitor (PI), an immunomodulators (IMiD) and anti-CD38 mAb.
Background: Multiple myeloma is a malignant neoplasm of plasma cells in the bone marrow. While, therapeutics advances have been made in MM, substantial challenges and unmet needs exist for RRMM. Limited treatment options are available for triple-refractory patients (PI, IMiD and mABs) with most therapies showing low, short duration responses (ORR: 20-30%) and poorer survival. CAR-Ts have emerged as promising treatment approaches for various lymphomas and leukemias. B-cell maturation antigen (BCMA) is highly expressed on MM cells and thus, is a suitable therapeutic target. ​
Details: The approval was based on the pivotal Ph 2 KarMMa study evaluating ide-cel in 127 heavily pre-treated and highly refractory MM patients with an IMiD, a PI and anti-CD38 Ab. In 100 efficacy evaluable patients (88% with 4+ prior therapies, 85% triple-class refractory) ORR was 72% (sCR: 28%) with rapid and durable responses (mTTR: 30 days, mDOR: 11 month). Patients with sCR showed mDOR of 19 months with 65% achieving remission that lasted ≥12 months.
Abecma showed predictable and established safety profile and is approved with black box warning for CRS, neurotoxicities, HLH/MAS and prolonged cytopenias. It will require a one-time infusion with CAR-positive cells.
Implications: The approval makes Abecma the first, anti-BCMA personalised immunotherapy for RRMM patients and BMS the only company with two CAR-T approvals (Breyanzi was approved in Feb 2021 for R/R LBCL).
Abecma will be manufactured at BMS’ New Jersey facility and be strictly available under a Risk Evaluation and Mitigation Strategy (REMS) program, the ABECMA REMS, along with support on celltherapy360. Abecma will be priced at $419,500 with analysts expecting sales of >$2.5 billion by 2030.
Similar or other key competing modalities include BCMA ADCs - GSK’s Blenrep (BCMA ADC approved in August 2020), AstraZeneca’s MEDI2228; anti-BCMA CAR-Ts - JNJ’s cilta-cel (rolling submission in December 2020), CARsgen Therapeutics’ CT053; anti-BCMA BiTEs - Amgen's AMG 701, Regeneron’s REGN5458, AbbVie/Teneobio’s TNB-383B.
Collated by : Shilpa Rawal, PhD
Drug Approvals
FDA Approves KEYTRUDA® + Platinum- and Fluoropyrimidine-Based Chemotherapy for Treatment of Certain Locally Advanced or Metastatic GEJ Patients
“Because esophageal cancer generally has poor survival rates, new first-line therapies are urgently needed for these patients,” said Dr. Peter Enzinger, Director, Center for Esophageal and Gastric Cancer, Dana-Farber/Brigham and Women’s Cancer Center. “Today’s approval of this indication for KEYTRUDA introduces a new option, which has shown a superior survival benefit compared to FU and cisplatin alone, for newly diagnosed patients with locally advanced or metastatic esophageal or GEJ carcinoma that is not amenable to surgical resection or definitive chemoradiation, regardless of PD-L1 expression status and tumor histology.”

Pemazyre® (pemigatinib) approved in Japan for the Treatment of BTC Patients with FGFR2 Fusion Gene, Worsening After Cancer Chemotherapy
“The MHLW approval of Pemazyre is an important milestone for the BTC community, and underscores our commitment to finding and delivering solutions for patients with significant unmet medical needs,” said Lothar Finke, M.D., Ph.D., General Manager, Incyte Asia. “BTC is a rare and serious condition, and we are proud that with the support of the MHLW we will be able to bring a new targeted treatment to more patients around the world.”
Regulatory News
EMA Accepts MAA for Enfortumab Vedotin; to be reviewed under accelerated assessment for the treatment of locally advanced or metastatic urothelial cancer
“In the European Union, it is estimated that 118,000 people are diagnosed with urothelial cancer each year, and 52,000 die as a result of the disease,” said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. “People with advanced urothelial cancer face an urgent need for new treatment options, which is reflected in the CHMP’s decision to grant accelerated assessment. We will continue to work with the CHMP toward our goal of securing marketing authorization as soon as possible.”
FDA Grants Two New Breakthrough Device Designations for Signatera™ MRD Test
"We are committed to working with the FDA and with our biopharma partners to validate the use of the Signatera MRD test across a broad range of solid tumor indications," said Fayyaz Memon, Vice President of Regulatory Affairs at Natera. "These two new Breakthrough Device Designations will help us accelerate our mission to bring life-saving diagnosis and treatment to cancer patients as early as possible."
Click here for more Regulatory News
Trial Results
Ph 3 RELATIVITY-047 Trial of Relatlimab and Opdivo in Patients with Previously Untreated Metastatic or Unresectable Melanoma Meets Primary Endpoint of PFS improvement
“Immune checkpoint inhibitors alone or in combination have transformed treatment and improved survival rates for patients with metastatic or unresectable melanoma. However, there remain a considerable number of patients who could benefit from a novel combination therapy that leverages potentially complementary pathways to improve anti-tumor activity,” said Jonathan Cheng, senior vice president and head of oncology development, Bristol Myers Squibb. “The results of this study suggest that targeting the LAG-3 pathway in combination with PD-1 inhibition may be a key strategy to enhance the immune response and help improve outcomes for these patients.”
Ph 3 IMpower010 study of Tecentriq® (atezolizumab), compared with best supportive care (BSC), met its primary endpoint of DFS at the interim analysis
“With these landmark results, Tecentriq has become the first cancer immunotherapy to help many people with resectable early lung cancer live longer without their cancer returning," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We’re excited by the clinical benefit adjuvant Tecentriq may bring to lung cancer patients, particularly in the PD-L1-positive population. We will submit these data to regulatory authorities as soon as possible.”
Click here for more Trial Results
Trial/Program Status
First Patient Dosed in Ph 2a Portion of Basket Study Evaluating NT-I7 (efineptakin alfa) and KEYTRUDA® (pembrolizumab) in Relapsed/Refractory Advanced Solid Tumors
“We are excited to quickly advance to the Phase 2a portion of this important clinical trial to further evaluate this combination treatment in patients with a variety of advanced solid tumors,” said NgocDiep Le, M.D., Ph.D., Executive VP and Chief Medical Officer of NeoImmuneTech. “We have great confidence in the combination of NT-I7, as a T cell amplifier, with CPI therapies like KEYTRUDA to improve clinical outcomes and become a viable treatment option for many cancer patients, with either CPI-responsive or CPI-resistant tumors.”
Development of Tesetaxel Discontinued
“We thank the investigators, study team personnel, and especially the patients and their caregivers for their endeavors to improve treatments for patients with breast cancer,” said Kevin Tang, Chief Executive Officer of Odonate.
Click here for more Trial Statuses
Collated by : Richa Tewari, PhD
Genes and Therapy
Gene therapy not the cause of cancer in haemophilia patient, announces uniQure
uniQure announced that the vector virus is not the cause of hepatocellular carcinoma (HCC) in the single patient who developed HCC in its HOPE-B haemophilia gene therapy trial. The investigation results suggest that the virus inserted into the genome in only a tiny fraction (0.027%) of the cells, and when it did, it landed in randomly scattered spots. If the virus had triggered a single cell to grow out of control, the viral DNA would have shown up in the same spot in lots of the tumor cells. Additional whole genome sequencing of the tumor confirmed that the patient had several genetic mutations that are characteristic of HCC and are independent of vector integration. Finally, gene expression analysis of the tumor and adjacent tissue suggested a precancerous state in the liver consistent with several risk factors that predispose this patient to HCC.
NurOwn® cell therapy found effective for progressive multiple sclerosis in Phase II clinical trial
BrainStorm Cell Therapeutics found positive results from its multi-center, open-label Phase II trials (NCT03799718) for the safety and efficacy of NurOwn®stem cell therapy for progressive multiple sclerosis in 20 patients. NurOwn® is produced from a patient’s own bone marrow-derived mesenchymal stem cells (MSCs). Under specific stimulating conditions, MSCs release neurotrophic factors (NTFs). The patients were administered three injections of 100-125 million autologous MSC-NTF cells intrathecally at 2-month intervals. These factors induce the growth and development of brain cells. The trial showed appreciative results for patients’ functional, mental and visual abilities. Progressive multiple sclerosis is a chronic neuroinflammatory and neurodegenerative disorder with few treatment options available presently.
Click here for more on Genes and Therapy
MedNess Business
BioPharma News
Omega Therapeutics announces $126 million in series C financing for developing ‘programmable epigenetic medicines’ against a range of disease conditions
Omega Therapeutics (Omega, Cambridge, MA) is a development-stage company that owns the platforms Omega Epigenomic Programming™ Platform and Omega Epigenomic Controllers™, to examine Insulated Genomic Domains (IGDs). IGDs acquire specific 3D DNA architecture, bringing together regulators for epigenetic expression. Omega’s platforms have mapped 15000 IGDs as ‘zipcodes’ or genomic addresses to new drug targets. These targets also include the present class of ‘undruggable proteins’. By doing this, Omega is able to provide therapeutics for precise up/down regulation of single or multi-gene expression with controlled durability, at the pre-transcriptional stage, without altering the genetic code. Omega plans to apply its technology to oncology, regenerative medicine, inflammation, autoimmune, metabolic and rare genetic diseases.
For its technology and vision, Omega has raised $126 million in series C funding from Flagship Pioneering (lead investor), followed by Invus, Fidelity Management & Research Company, funds and accounts managed by BlackRock, Cowen, Point72, Logos Capital and Mirae Asset Capital.
Omega’s pre-clinical program OTX-2002, has potently downregulated c-MYC expression in hepatocellular carcinoma, which has previously been tried without success by conventional wet lab approaches. OTX-2002 is now being advanced into Investigational New Drug (IND)-enabling studies. Omega further plans to use its funding towards developing novel candidates for regenerative medicine, inflammatory diseases, acute respiratory distress syndrome (ARDS) associated with COVID-19, alopecia, neutrophilic dermatoses, non-small cell lung cancer (NSCLC).
Onco-News
U.S. Commercial Availability of FOTIVDA® (tivozanib) for the Treatment of Adult Patients With R/R Advanced RCC Announced Ahead of Previous Guidance
“We are thrilled to begin bringing FOTIVDA to patients battling relapsed or refractory kidney cancer,” said Michael Bailey, president and chief executive officer of AVEO. “With its differentiated tolerability and efficacy profile, FOTIVDA has the potential to serve as a meaningful, evidence-based treatment option for the population of patients who have previously received two prior lines of systemic therapy.”
Click here for more on mergers, acquisition and business news
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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