Regulatory Decision Summary for Elahere

The purpose of this New Drug Submission (NDS) was to seek marketing authorization for Elahere (mirvetuximab soravtansine for injection) as a monotherapy 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.

After review, the indication recommended for authorization is:

Elahere (mirvetuximab soravtansine for injection) as monotherapy 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 (See 4.1. Dosing Considerations).

This submission was filed under the Priority Review Policy.

The sponsor consented to information sharing between Health Canada and health technology assessment organizations as part of an aligned review pathway.

The recommendation for market authorization of Elahere was based on the results of Study IMGN853-0416 (MIRASOL), a randomized, open-label, Phase 3 study of mirvetuximab soravtansine (MIRV) vs. Investigator’s choice of chemotherapy (IC Chemo) in adult female patients with platinum-resistant advanced high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancers whose tumours were positive for folate receptor-alpha (defined as ≥ 75% of tumour staining at ≥ 2+ intensity by immunohistochemistry) who had received one to three prior systemic treatment regimens. Approximately 453 patients were randomized in a 1:1 ratio into the MIRV arm (N = 227) or the IC Chemo arm (N = 226). The primary efficacy endpoint of the study was Investigator-assessed Progression Free Survival (PFS). Secondary efficacy endpoints included confirmed Objective Response Rate by Investigator (ORR) and Overall Survival (OS).

The trial demonstrated statistically significant improvements in both the primary and secondary efficacy endpoints of the study. The median PFS was 5.62 months (95% confidence interval [CI]: 4.34, 5.95) in the MIRV arm compared to 3.98 months (95% CI: 2.86, 4.47) in the IC Chemo arm with a Hazard Ratio (HR) of 0.65 (95% CI: 0.521, 0.808; p < 0.0001), representing a 35% reduction in the risk of disease progression or death in the MIRV arm. The ORR by Investigator was 42.3% (95% CI: 35.8, 49.0) in the MIRV arm compared to 15.9% (95% CI: 11.4, 21.4) in the IC Chemo arm (p < 0.0001). Of the responders, there were 12 (5%) complete responses (CRs) and 84 (37%) partial responses (PRs) in the MIRV arm compared to zero (0%) CRs and 36 (16%) PRs in the IC Chemo arm. With a median follow-up of 13.11 months, the median OS was 16.46 months (95% CI: 14.46, 24.57) for the MIRV arm compared to 12.75 months (95% CI: 10.91, 14.36) for the IC Chemo arm) with a HR of 0.67 (95% CI: 0.504, 0.885; p = 0.0046), representing a 33% reduction in the risk of death in the MIRV arm.

The most common (≥ 20% incidence) treatment-emergent adverse events (TEAEs) reported in patients treated with MIRV were vision blurred, keratopathy, abdominal pain, fatigue, diarrhea, dry eye, constipation, nausea, and peripheral neuropathy. Ocular disorders, peripheral neuropathies and pneumonitis were considered important identified risks associated with MIRV. Serious adverse reactions occurred in 24% of patients treated with MIRV; the most common serious adverse reactions were pleural effusion (3%) and small intestinal obstruction (2%). Seven treatment-related fatal adverse events were reported among patients receiving MIRV including intestinal obstruction, dyspnea in the setting of subileus, neutropenic sepsis, cardiopulmonary failure, respiratory failure, ischemic stroke and pulmonary embolus. The safety findings and applicable risk mitigation and risk management measures are described in the Elahere product monograph (PM).

An updated Risk Management Plan (RMP) for Elahere was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for Elahere has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and PM were considered to be acceptable.

Overall, the benefit/risk profile of Elahere is favourable in the target patient population when used under the conditions of use recommended in the approved Elahere PM. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Elahere, including dosing, please refer to the PM approved by Health Canada and available through the Drug Product Database.