AbbVie has received marketing authorization from the European Commission for Elahere (mirvetuximab soravtansine) for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens. This approval marks a significant advancement in the treatment landscape for this challenging cancer. Elahere is the first and only folate receptor alpha (FRα)-directed antibody drug conjugate (ADC) medicine approved in the European Union (EU), as well as Iceland, Liechtenstein, Norway, and Northern Ireland.
Clinical Significance
The approval of Elahere addresses a critical unmet need in the treatment of platinum-resistant ovarian cancer. Ovarian cancer is a leading cause of death from gynecological cancers worldwide, with most patients presenting with late-stage disease. While initial treatment typically involves surgery followed by platinum-based chemotherapy, many patients eventually develop platinum-resistant disease, leaving limited treatment options. These options often result in adverse events that negatively impact the quality of life.
Supporting Data from the MIRASOL Trial
The marketing authorization was supported by data from the Phase 3 MIRASOL trial, a global, open-label, randomized, controlled study. The trial enrolled 453 patients with platinum-resistant, high-grade serous ovarian cancer whose tumors expressed high levels of FRα (≥75% of cells with ≥2+ staining intensity), confirmed using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay. Participants had previously received one to three lines of prior therapy.
The primary endpoint was investigator-assessed progression-free survival (PFS). Key secondary endpoints included objective response rate (ORR) and overall survival (OS).
Results from the MIRASOL trial, presented at the 2023 ASCO Annual Meeting, demonstrated:
- A 35% reduction in the risk of tumor progression or death in patients treated with Elahere compared to investigator's choice (IC) chemotherapy (HR 0.65, 95% CI: 0.52, 0.81; p<0.0001).
- Improvement in OS compared with IC chemotherapy, representing a 33% reduction in the risk of death in the Elahere arm (HR 0.67, 95% CI: 0.50, 0.89; p=0.0046).
Companion Diagnostic
The VENTANA FOLR1 (FOLR1-2.1) RxDx Assay, developed in collaboration with Roche Diagnostics, is a crucial component of Elahere's treatment strategy. This immunohistochemistry (IHC) assay identifies patients whose tumors express high levels of FRα, allowing clinicians to select those most likely to benefit from Elahere therapy.
Mechanism of Action
Elahere is a first-in-class ADC composed of a folate receptor alpha binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells.
Safety Profile
The most common adverse reactions observed with Elahere in clinical trials included blurred vision, nausea, diarrhea, fatigue, and abdominal pain. Healthcare professionals are advised to monitor patients for ocular toxicity, pneumonitis, and peripheral neuropathy, and to adjust the dosage accordingly.
Impact on Patient Care
"The approval of ELAHERE by the European Commission provides a much needed clinically meaningful option for patients who receive the heartbreaking news their ovarian cancer has returned, fearing what's next in their treatment journey after they've developed platinum-resistance," said Roopal Thakkar, M.D., executive vice president, research and development, chief scientific officer, AbbVie.
