The U.S. Food and Drug Administration (FDA) has made a significant advancement in the treatment of ovarian cancer by approving Verastem's AVMAPKI FAKZYNJA CO-PACK, a combination therapy for patients with KRAS-mutated recurrent low-grade serous ovarian cancer (LGSOC). This groundbreaking approval, granted on May 8, 2025, marks the first-ever FDA-approved treatment specifically targeting this rare and challenging form of ovarian cancer.
Prior to this approval, there were no FDA-approved therapies for KRAS-mutated recurrent LGSOC, a cancer that is not only rare but also notoriously difficult to treat. The approval was based on promising results from the Phase 2 RAMP 201 clinical trial, which demonstrated a 44% overall response rate among patients receiving the treatment.
Verastem Oncology, the company behind this innovative therapy, plans to make AVMAPKI FAKZYNJA CO-PACK available by prescription within a week of the approval date. This expedited availability comes ahead of the anticipated Prescription Drug User Fee Act (PDUFA) action date of June 30, 2025, showcasing the FDA's commitment to accelerating access to new therapies for patients in need.
“Today’s approval of AVMAPKI FAKZYNJA CO-PACK for patients with KRAS-mutated recurrent low-grade serous ovarian cancer represents not only the first-ever FDA-approved treatment specifically for this rare cancer but also a new day for people living with this disease who have been in desperate need of new treatment options,” stated Dan Paterson, president and CEO of Verastem Oncology.
The combination therapy consists of two oral medications: avutometinib and defactinib. Avutometinib inhibits MEK kinase activity, while defactinib acts as a FAK inhibitor, together targeting the RAS/MAPK pathway, which is known to drive the growth and drug resistance of certain tumors. This dual approach is designed to provide a more comprehensive treatment option for patients.
The RAMP 201 trial involved 57 adult patients with measurable KRAS-mutated recurrent LGSOC who had previously undergone at least one line of systemic therapy, including platinum-based chemotherapy. Participants received AVMAPKI at a dosage of 3.2 mg orally twice weekly for the first three weeks of a four-week cycle, along with FAKZYNJA at 200 mg orally twice daily for the same duration. The study assessed the overall response rate (ORR) as the primary efficacy outcome.
“Low-grade serous ovarian cancer is a rare and highly recurrent cancer with limited effective treatment options. This first-ever FDA approval in this disease was based on the primary analysis of the Phase 2 RAMP 201 trial, in which the combination of avutometinib and defactinib resulted in a significant overall response rate for patients with a KRAS mutation while being generally well tolerated,” said Dr. Rachel Grisham, Section Head of Ovarian Cancer at Memorial Sloan Kettering Cancer Center.
Nicole Andrews, chair of the STAAR Low-Grade Serous Ovarian Cancer Foundation, expressed her sentiments regarding the approval: “One of the most devastating aspects of my LGSOC diagnosis was learning there are no FDA-approved treatments for this rare cancer. While there were some treatment options at the time that I could try, I made it my mission to advocate for research specific to my disease. Today we're celebrating a milestone with the first-ever FDA-approved treatment option specifically for patients with recurrent LGSOC with a KRAS mutation.”
The AVMAPKI FAKZYNJA CO-PACK is expected to provide new hope for the approximately 6,000 to 8,000 women diagnosed with low-grade serous ovarian cancer each year in the United States. The approval not only signifies a medical breakthrough but also emphasizes the importance of continued research and advocacy for rare cancers.
Verastem's commitment to innovation in cancer treatment is evident in its ongoing clinical trials and the establishment of the Verastem Cares™ program, which aims to provide patient access and reimbursement support. This initiative is crucial for ensuring that patients can benefit from the new therapy without facing financial barriers.
As the AVMAPKI FAKZYNJA CO-PACK becomes available, Verastem will hold an investor conference call to discuss the implications of this approval for both patients and the market. This event is scheduled for May 8, 2025, at 2:30 PM ET, and will be accessible via a live audio webcast on the company’s website.
The safety profile of AVMAPKI FAKZYNJA CO-PACK has been evaluated, with potential side effects including ocular disorders, skin toxicities, hepatotoxicity, and rhabdomyolysis. Common side effects reported include nausea, fatigue, and rash. Patients are advised to undergo regular monitoring to manage any adverse reactions effectively.
In summary, the FDA's approval of AVMAPKI FAKZYNJA CO-PACK represents a significant step forward in the treatment of KRAS-mutated recurrent low-grade serous ovarian cancer. This therapy not only addresses a critical unmet need but also provides a beacon of hope for patients and advocates who have long awaited effective treatment options.
As the medical community and patients alike look forward to the rollout of this new therapy, the focus remains on improving outcomes and quality of life for those affected by this challenging disease.
