Immunogen has submitted a Biologics License Application (BLA) under the accelerated approval pathway to the US Food and Drug Administration (FDA) for mirvetuximab soravtansine monotherapy in patients with folate receptor alpha (FRα)-high platinum-resistant ovarian cancer who have been previously treated with 1 to 3 prior systemic treatments.

Mark Enyedy Mr. Enyedy joined ImmunoGen as President and Chief Executive Officer in 2016, bringing over twenty-five years of combined general management, business development, and legal experience in the biotechnology industry. Prior to ImmunoGen, he served as Executive Vice President and Head of Corporate Development for Shire plc leading the company’s Strategy, M&A, and Corporate Planning functions and providing commercial oversight for the company’s pre-Phase 3 portfolio. Previously, Mr. Enyedy served as CEO of Proteostasis Therapeutics, Inc., following 15 years at Genzyme Corporation in diverse roles, most recently as President of the Transplant, Oncology, and Multiple Sclerosis divisions. Before joining Genzyme, Mr. Enyedy was an associate with the law firm Palmer & Dodge. He holds a J.D. from Harvard Law School and a B.S. from Northeastern University. Mr. Enyedy also serves on the Board of Directors of Akebia Therapeutics, Inc. and The American Cancer Society of Eastern New England. He previously served on the Board of Directors of Fate Therapeutics, Inc. and Keryx Biopharmaceuticals, Inc.
Mark Enyedy is President and Chief Executive Officer of ImmunoGen.

Mirvetuximab soravtansine, previously known as IMGN853, is a FRα-targeting antibody-drug conjugate or ADC being developed by ImmunoGen. The drug comprises a folate receptor α (FRα)-binding antibody conjugated, via the hindered disulfide sulfo-SPDB linker, to the maytansinoid DM4, a potent cancer-cell killing agent developed specifically for use in ADCs.

BLA submission
The submission is based on results from the pivotal Phase 3 SORAYA trial. Top-line data from SORAYA were announced in November 2021 and full data from the study were presented this month at the Society of Gynecologic Oncology (SGO) 2022 Annual Meeting in Phoenix, AZ.

“The BLA submission for mirvetuximab soravtansine is a key inflection point on our journey to delivering a safe and effective treatment option to patients with platinum-resistant ovarian cancer and moves us one step closer to transforming ImmunoGen into a fully-integrated oncology company,” explained Mark Enyedy, ImmunoGen’s President and Chief Executive Officer.

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Unmet medical need
“Platinum-resistant ovarian cancer is an area with high unmet need,” Enyedy said.

Despite the introduction of targeted and immunological therapies for its management, the backbone of therapy for patients diagnosed with platinum-resistant ovarian cancer, remains platinum-based chemotherapy with carboplatin or cisplatin. Research shows that up to 25% of women with ovarian cancer have innately (or primary) platinum-refractory disease. Most patients are sensitive to front-line platinum therapy and will unfortunately develop recurrence and acquire progressive resistance over time. [1]

Ovarian Cancer [1] NIH SEER Data: Estimated New Cases, 2021. Image: Immunogen 2022.
The outcome of patients with platinum-resistant ovarian cancer is generally poor, with low response rates to further chemotherapy and a median survival of less than 12 months.[1]

However, depending on the duration of remission, recurrent disease can be re-challenged with platinum drugs, often alongside another chemotherapeutic drug or a molecularly targeted agent such as niraparib (Zejula®; GlaxoSmithKline/GSK), an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer and olaparib (Lynparza®; AstraZeneca), a PARP inhibitor that has shown efficacy in a phase 2 study when given in capsule formulation to all-comer patients with platinum-sensitive, relapsed high-grade serous ovarian cancer. [2][3]

Invariably, patients with innate or acquired resistance converge on the common endpoint of progressive, platinum-resistant cancer in which life expectancy and further treatment options are restricted.

Based on the positive results of the results of the SORAYA study, “we look forward to working with FDA to secure mirvetuximab soravtansine’s first approval and bringing this novel therapy to patients as quickly as possible,” Enyedy noted.

Review process
The FDA has a 60-day review period to determine whether the BLA is complete and acceptable for filing. ImmunoGen has requested priority review of the application and, if granted, the review will be completed within six months of the filing date.

The BLA was submitted under the FDA’s accelerated approval pathway, instituted to allow for expedited development of drugs that treat serious conditions and provide a meaningful advantage over available therapies based on a surrogate endpoint. ImmunoGen continues to enroll patients in the confirmatory MIRASOL trial designed to generate the randomized data needed for full approval and expects to announce top-line data from this study in the third quarter of 2022.

The FDA granted Orphan Drug Designation to mirvetuximab soravtansine for the treatment of ovarian cancer in April 2015. In June 2018, the FDA granted mirvetuximab soravtansine Fast Track Designation for the treatment of patients with medium to high FRα-positive platinum-resistant ovarian cancer who received at least one, but no more than three, prior systemic treatment regimens, and for whom single-agent chemotherapy is appropriate as the next line of therapy. This designation is intended to facilitate the development and expedite the review of drugs that treat serious and life-threatening conditions.

Clinical trials
A Study of Mirvetuximab Soravtansine in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression (SORAYA) – NCT04296890 
A Study of Mirvetuximab Soravtansine vs. Investigator’s Choice of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha Expression (MIRASOL) –NCT04209855

Highlights of prescribing information
Carboplatin (Paraplatin® Bristol-Myers Squibb/BMS)(prescribing information)
Cisplatin (Platinol®; Bristol-Myers Squibb/BMS)(prescribing Information)
Niraparib (Zejula®; GlaxoSmithKline/GSK) (prescribing information)
Olaparib (Lynparza®; AstraZeneca) (prescribing information)

Reference
[1] Davis A, Tinker AV, Friedlander M. “Platinum resistant” ovarian cancer: what is it, who to treat and how to measure benefit? Gynecol Oncol. 2014 Jun;133(3):624-31. doi: 10.1016/j.ygyno.2014.02.038. Epub 2014 Mar 4. PMID: 24607285.
[2] Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016 Dec 1;375(22):2154-2164. doi: 10.1056/NEJMoa1611310. Epub 2016 Oct 7. PMID: 27717299.
[3] Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510. PMID: 28754483.

Featured image: Research. Photo Courtesy: © 2016 – 2022 Fotolia/Adobe. Used with permission

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