On November  14, 2022 the US Food and Drug Administration (FDA) granted accelerated approval to mirvetuximab soravtansine-gynx (Elahere®ImmunoGen), for the treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received one to three prior systemic treatment regimens.

The accelerated approval was based on the Objective Response Rate (ORR), an assessment of the Tumor Burden (TB) after a given treatment in patients with solid tumors, and Duration of Response (DoR) data from the pivotal SORAYA trial (NCT04296890).

Patients are selected for therapy based on the FDA-approved VENTANA FOLR1 (FOLR-2.1) RxDx Assay, a  companion diagnostic device to select patients for treatment.

Mirvetuximab soravtansine-gynx is  a first-in-class antibody-drug conjugate (ADC) which includes a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells.

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DM4 is a second-generation maytansine derivative which disrupts tubulin resulting in mitotic arrest and apoptosis and is between 100-1000 fold more potent than vinca alkaloids DM4 also diffuses through the cell membrane allowing bystander killing of adjacent tumor cells.

Accelerated approval
Following the accelerated approval, Immunogen conducted the Phase 3 MIRASOL confirmatory trial (NCT04209855; GOG 3045/ENGOT OV-55). Based on positive top-line data from the MIRASOL trial, which was designed to evaluating the safety and efficacy of mirvetuximab soravtansine-gynx compared to chemotherapy in patients with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer who have received one to three prior lines of therapy, ImmunoGen plans to submit a Marketing Authorization Application (MAA) in Europe and a supplemental Biologics License Application (sBLA) in the US for the conversion to a regular approval of mirvetuximab soravtansine-gynx.

Unmet medical need
For the past 3 decades, platinum-based chemotherapy has been the standard of care for patients diagnosed with ovarian cancer.  And while the majority of patients respond to platinum-based treatment, the emergence of platinum resistance in recurrent ovarian cancer is inevitable during the disease course. And outcomes for these patients are poor, with limited treatment options, highlighting the unmet need for new treatment options. [1] The unmet medical needs is exasperated by the fact that most women with ovarian cancer present with Stage III or IV disease, contributing to high mortality rate. [2]

Expected sales volume
According to GlobalData, a leading data and analytics company, sales of mirvetuximab soravtansine-gyn are expected to reach $615 million by 2029, registering a 114% compound annual growth rate (CAGR).

“The Standard of Care (SOC) for epithelial ovarian, fallopian, and primary peritoneal cancers has long been platinum therapies. Patients who become resistant to these therapies have been treated with non-platinum cytotoxic agents, including liposomal doxorubicin, paclitaxel, and topotecan, alone or in combination with bevacizumab (Avastin®; Genentech/Roche),” noted Israel Stern, Oncology & Hematology Analyst at GlobalData.

“Immunogen believes mirvetuximab soravtansine-gynx will replace these therapies as a SOC,” Stern added.

In the confirmatory study, mirvetuximab soravtansine-gynx outperformed the investigator’s choice (IC) of chemotherapies in various clinical metrics, including median progression-free survival of 5.6 months in the mirvetuximab soravtansine-gynx arm vs. 4 months in the IC arm, in addition to an improvement in median overall survival of 16.5 months compared to 12.8 months and objective response rates of 42.3% vs. 15.9%.

The drug’s safety profile primarily consists of low-grade ocular and gastrointestinal events and has lower rates of grade ≥3 adverse events.

“With the data from MIRASOL, Immunogen is poised to receive the full FDA nod as well as market access in Europe. A key to an expanded patient pool  is mirvetuximab soravtansine-gynx.’s potential clinical benefit for patients who have platinum-sensitive ovarian disease,” Stern observed.

Ongoing studies
Immunogen currently has two ongoing trials for platinum-sensitive ovarian cancer: PICCOLO (NCT05041257) , a Phase ll study, and GLORIOSA (NCT05445778), a Phase lll study where mirvetuximab soravtansine-gynx is administered in combination with Avastin.

“The likely full approval of mirvetuximab soravtansine-gynx is great news for Immunogen and its investors. Data from the ongoing trials will go a long way toward forecasting the true revenue potential for the drug,” Stern said.

“One thing is for certain, Immunogen will continue to utilize their successful proprietary ADC technology to develop new agents across the cancer spectrum,” Stern concluded.

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
Mirvetuximab Soravtansine Monotherapy in Platinum-Sensitive Epithelial, Peritoneal, and Fallopian Tube Cancers (PICCOLO) – NCT05041257
Mirvetuximab Soravtansine With Bevacizumab Versus Bevacizumab as Maintenance in Platinum-sensitive Ovarian, Fallopian Tube, or Peritoneal Cancer (GLORIOSA) – NCT05445778

Highlights of Prescribing Information
Mirvetuximab soravtansine-gynx (Elahere®; ImmunoGen)[Prescribing Information]
Bevacizumab (Avastin®; Genentech/Roche)[Prescribing Information]

RxDx Diagnostic Assay
VENTANA FOLR1 (FOLR1-2.1) RxDx Assay [Predictive IHC assay]

Indication and Usage
Mirvetuximab soravtansine-gynx is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test.This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

[1] Richardson DL, Eskander RN, O’Malley DM. Advances in Ovarian Cancer Care and Unmet Treatment Needs for Patients With Platinum Resistance: A Narrative Review. JAMA Oncol. 2023 Apr 20. doi: 10.1001/jamaoncol.2023.0197. Epub ahead of print. PMID: 37079311.
[2] Roett MA, Evans P. Ovarian cancer: an overview. Am Fam Physician. 2009 Sep 15;80(6):609-16. PMID: 19817326.

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