FDA Approves Verastem's Oral Combo for Rare Ovarian Cancer

Verastem Oncology recently achieved a significant milestone with the FDA granting accelerated approval for its oral combination treatment targeting a rare form of ovarian cancer. The treatment, known commercially as Avmapki Fakzynja Co-Pack, is specifically designed for patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC). This condition affects approximately 6,000 to 8,000 women in the United States and around 80,000 globally. Avmapki Fakzynja Co-Pack stands out as the first oral combination therapy of two novel drugs approved in oncology, according to Verastem, and it aims to supplant chemotherapy as the standard treatment for LGSOC.

The FDA's decision came earlier than expected, coinciding with World Ovarian Cancer Day, and was made over seven weeks ahead of the target decision date of June 30. Verastem's CEO, Dan Paterson, expressed the company's enduring commitment to addressing this unmet need in the patient community, highlighting the satisfaction of providing a new option for those who previously had limited treatment alternatives.

Based in Needham, Massachusetts, Verastem intends to price the treatment at $48,500 for a 28-day regimen. This includes two 3.2 mg doses of Avmapki per week and daily 200 mg doses of Fakzynja. The average treatment duration is estimated to be 18 months. Mike Crowther, Verastem's chief commercial officer, acknowledged the challenge of pricing two novel therapies simultaneously, noting that similar approvals in rare oncology indications typically range between $45,000 and $55,000.

Verastem is prepared to launch Avmapki Fakzynja Co-Pack imminently, with expectations for a gradual initial uptake. Approximately half of the diagnosed patients are treated across 100 specialized centers, which may influence the rollout strategy. Analyst Graig Suvannavejh from Mizuho Securities projects peak sales for this indication to be between $700 million and $900 million. The combination therapy has also demonstrated potential in early-stage trials for first-line pancreatic cancer.

Verastem, founded in 2010, focuses on developing cancer drugs targeting cancer stem cells. The company was co-founded by Christoph Westphal and Michelle Dipp, with research roots from MIT biologists Piyush Gupta, Eric Lander, and Robert Weinberg. In 2012, Verastem secured in-licensed rights to focal adhesion kinase (FAK) inhibitor defactinib from Pfizer, which plays a role in regulating tumor cell proliferation and invasion. This pathway's disruption had shown positive results in preclinical models.

In 2016, Verastem acquired rights to the RAF/MEK inhibitor avutometinib from Pfizer and Merck KGaA. The goal was to pair it with defactinib, which had underperformed in early-stage mesothelioma trials. Avutometinib distinguishes itself by blocking both MEK kinase activity and RAF's ability to phosphorylate MEK, offering a unique mechanism compared to other MEK inhibitors.

The approval of Avmapki Fakzynja Co-Pack was based on results from a phase 2 trial involving 57 patients who had previously received at least one systemic therapy, including platinum-based regimens. Verastem is currently conducting a phase 3 trial, RAMP 301, comparing the combination against standard chemotherapy or hormonal therapy for recurrent LGSOC, both with and without KRAS mutations.

LGSOC represents a small percentage of all ovarian cancer cases, around 2% to 5%. The disease tends to affect a younger demographic, with about 80% of patients experiencing recurrence after remission. It also has a high mortality rate, with a median survival of approximately 10 years.