Ovarian cancer patients whose disease develops resistance to platinum-based chemotherapies have few treatment alternatives. A new ovarian cancer drug that won a speedy FDA nod last fall now has data from a confirmatory study that clinicians say should support the drug’s full approval. They also say the new therapy, Elahere, will change the care of ovarian cancer.

In Phase 3 results presented Sunday during the annual meeting of the American Society of Clinical Oncology in Chicago, Elahere shrunk tumors and helped ovarian cancer patients live longer compared to chemotherapies. But this drug, developed by Waltham, Massachusetts-based ImmunoGen, treats only patients whose tumors exhibit a particular biological marker.

Elahere, known in development as mirvetuximab soravtansine, targets folate receptor alpha, a protein abundant on the surface of ovarian cancer cells. The drug is approved for treating patients whose expression of this protein is classified as high. The FDA approved a companion diagnostic from Roche Diagnostics that tests protein levels to determine a patient’s suitability for the ImmunoGen drug, an antibody drug conjugate (ADC) comprised of a toxic payload directed to its destination by a tumor-targeting antibody. The FDA’s accelerated approval for Elahere last November made it the first ADC approved for ovarian cancer.

The last time the FDA approved a therapy for platinum-resistant ovarian cancer was in 2014, a decision that went to Roche’s Avastin. The main goal of the confirmatory Phase 3 test of Elahere was to measure progression-free survival, which is how long patients live without their disease worsening. Overall survival, measured from when patients were randomized in the study until death, was a secondary goal. The median follow-up with patients in this study was 13.1 months.

In 281 women who previously received Avastin, results showed progression-free survival with the ImmunoGen drug was 36% better and overall survival was 26% better in the Elahere arm compared to the physician’s choice of chemotherapy. In a group of 172 women who had not previously received Avastin, progression-free survival was 34% better and overall survival was 49% better in the study drug arm compared with the physician’s choice of chemo. Dr. Kathleen Moore, a University of Oklahoma professor of gynecologic oncology and the principal investigator of Elahere’s Phase 3 study, presented the results at the ASCO meeting.

“These data are practice changing and position mirvetuximab as a new standard of care for patients with folate receptor alpha-positive platinum-resistant ovarian cancer,” she said.

Elahere has already changed practice at City of Hope, said Dr. Thanh Dellinger, a gynecologic oncologist at the Duarte, California-based comprehensive cancer center. Since the drug’s accelerated approval, Dellinger used the drug in the treatment of patients who are folate receptor alpha positive high, she told MedCity News. Avastin and chemotherapies are “one-size fits all” treatments, but that approach doesn’t work for platinum-resistant ovarian cancer patients.

While Elahere is the first ADC for ovarian cancer, it’s the second biomarker-driven therapy for the disease. Patients are tested for BRCA mutations to determine whether they are eligible for another type of targeted drug called a PARP inhibitor. Now they’ll also need to be tested for folate receptor alpha.

“It’s another biomarker that we can use,” Dellinger said. “So ovarian cancer [treatment] has become much more biomarker driven.”

Standard of care chemotherapies cause systemic toxic effects. The targeting ability of an ADC is intended to keep the therapy’s toxic effects concentrated on the tumors, sparing healthy tissue.

On measures of safety, the adverse events in the Elahere Phase 3 study included low-grade eye and gastrointestinal problems, which is consistent with earlier studies. The drug’s label has a black box warning that alerts physicians and patients about the risk of eye problems including visual impairment; corneal damage; dry eye; sensitivity to light; pain; and uveitis, a type of inflammation inside the eye. Dellinger does not see the eye toxicity as a major problem, explaining that it can be managed with treatments such as steroid eye drops. She added that overall, the data reported at ASCO provide more information that she can use to counsel ovarian cancer patients.

Dr. Merry Jennifer Markum, a chief of the division of hematology and oncology at the University of Florida College of Medicine and an ASCO expert, said that Elahere is “very promising” for becoming a first-line treatment for ovarian cancer. Patients and their physicians want to postpone toxic chemotherapies until they’re really needed.

“Using a drug like this, that is better tolerated, allows us to perhaps go to this drug first and delay the toxic chemotherapy,” she said.

In a note sent to investors Monday, William Blair analyst Andy Hsieh said that on the heels of Elahere’s positive Phase 3 data, the short-term focus now shifts to the drug’s commercialization. ImmunoGen reported $29.5 million in first quarter 2023 sales for Elahere, which far exceeded William Blair estimates. The Phase 3 data could catalyze a collaboration agreement in Europe, bringing the company more capital to extend its cash runway.

Looking longer term, Hsieh noted that ImmunoGen is conducting additional clinical research that could support broadening the use of Elahere to more ovarian cancer patients and as part of combination therapies. The biotech is also developing a next-generation version of its drug that could address the spectrum of folate receptor alpha levels from low to high. Given the expression of this biomarker on other types of tumors, the drug may enable ImmunoGen to expand beyond ovarian cancer.

ImmunoGen said it plans to file an application seeking full FDA approval of Elahere in the second half of this year. A submission seeking approval in Europe is expected in the same time frame.

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