Verastem's Groundbreaking Approval: First Oral Combo Therapy for Rare Ovarian Cancer

In a significant milestone for both Verastem Oncology and patients with a rare form of ovarian cancer, the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Avmapki Fakzynja Co-Pack, a novel oral combination therapy. This landmark decision, announced on World Ovarian Cancer Day, marks Verastem's first FDA approval in its 15-year history and introduces the first treatment specifically designed for patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC).

A New Era in LGSOC Treatment

Avmapki Fakzynja Co-Pack, comprising avutometinib and defactinib, represents a paradigm shift in LGSOC treatment. This rare cancer affects between 6,000 and 8,000 women in the U.S. and 80,000 globally. The approval is based on promising results from a phase 2 trial involving 57 patients who had received at least one prior systemic therapy, including a platinum-based regimen.

Verastem CEO Dan Paterson expressed enthusiasm about the approval, stating, "We've been working to do this for a long time. We've had the pleasure of getting embedded into the patient community here and have just thoroughly enjoyed the ability to be able to offer something for these patients that haven't had anything before."

Commercial and Clinical Implications

The Needham, Massachusetts-based company has set the price for a 28-day regimen of Avmapki Fakzynja Co-Pack at $48,500. This includes two 3.2 mg doses per week of Avmapki and two daily 200 mg doses of Fakzynja, with patients typically remaining on therapy for an average of 18 months.

Mike Crowther, Verastem's chief commercial officer, contextualized the pricing decision: "It's difficult when you're pricing two novel-novel therapies simultaneously to get true analogs but if you look at the recent approvals across rarer indications in oncology, prices have ranged somewhere between $45,000 to $55,000."

Verastem is poised to make the treatment available next week, although the company anticipates a gradual initial launch trajectory. Approximately half of the diagnosed patients are concentrated in 100 centers, which may facilitate targeted distribution and adoption.

Mizuho Securities analyst Graig Suvannavejh, Ph.D., projects peak sales for this indication to range between $700 million and $900 million. Additionally, the combination therapy has shown promise in an early-stage trial for first-line pancreatic cancer, potentially broadening its future applications.

Scientific Background and Future Prospects

The development of Avmapki Fakzynja Co-Pack is rooted in Verastem's focus on targeting cancer stem cells. The company, co-founded in 2010 by investors Christoph Westphal and Michelle Dipp, was established to commercialize research from MIT biologists Piyush Gupta, Eric Lander, and Robert Weinberg.

Verastem acquired the rights to defactinib, a focal adhesion kinase (FAK) inhibitor, from Pfizer in 2012. FAK is a non-receptor tyrosine kinase that regulates tumor cell proliferation and invasion. In 2016, the company obtained rights to avutometinib, a RAF/MEK inhibitor, from Pfizer and Merck KGaA, specifically to pair with defactinib.

The unique mechanism of avutometinib allows it to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. This distinctive approach may contribute to the treatment's efficacy in LGSOC, a disease that affects a younger population and has a high recurrence rate, with approximately 80% of patients experiencing relapse after remission.

As part of the accelerated approval process, Verastem is conducting a confirmatory phase 3 trial, RAMP 301, comparing the combination therapy to standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC with and without a KRAS mutation. The results of this trial will be crucial in solidifying the long-term place of Avmapki Fakzynja Co-Pack in the treatment landscape for this challenging cancer.