8-K: Verastem Oncology Initiates Rolling NDA Submission for Avutometinib and Defactinib Combination in Ovarian Cancer

Verastem Oncology has begun the rolling submission of a New Drug Application to the FDA for accelerated approval of avutometinib and defactinib combination for recurrent KRAS mutant low-grade serous ovarian cancer.

Summary

• Verastem Oncology has initiated a rolling submission of a New Drug Application (NDA) to the FDA for accelerated approval of the combination of avutometinib and defactinib for adult patients with recurrent KRAS mutant low-grade serous ovarian cancer (LGSOC).
• The rolling submission allows the company to submit completed sections of the application for review before all sections are ready.
• The initial sections of the application include nonclinical and quality sections, with the clinical module expected to be submitted in the second half of 2024.
• The primary efficacy analysis will be based on the RAMP 201 study with 12 months of follow-up.
• The company plans to request a priority review of the NDA.
• The RAMP 201 trial treated 115 patients with recurrent LGSOC, with 109 patients eligible for efficacy evaluation.
• The confirmed objective response rate was 27% in all patients, 37% in KRAS mutant LGSOC, and 15% in KRAS wild-type LGSOC.
• 60% of evaluable patients achieved a clinical benefit rate of 6 months or longer.
• The median duration of therapy for all patients in Part A of the RAMP 201 trial was 11 months, with 18 months for KRAS mutant and 8 months for KRAS wild-type LGSOC.
• The company estimates that KRAS mutant LGSOC represents over two-thirds of the revenue opportunity.
• A commercial launch is planned targeting the top 400 healthcare providers and top 100 healthcare organizations, with a sales force of 14-18 representatives.

Sentiment

Score: 8

Explanation: The document is positive due to the initiation of the NDA submission and promising clinical trial results. The company has a clear path to potential approval and commercialization, although there are risks associated with regulatory approval and market adoption.

Positives

• The initiation of the rolling NDA submission is a significant step towards addressing the unmet needs of patients with recurrent KRAS mutant LGSOC.
• The combination therapy has shown robust and durable response rates in the RAMP 201 trial.
• The company has a clear plan for a focused commercial launch.
• The FDA has granted Breakthrough Therapy and Orphan Drug Designations, which may expedite the approval process.
• The company has a strong cash position of $110.1 million as of Q1 2024.

Negatives

• The market opportunity for the company's product candidates is difficult to estimate precisely.
• The company's estimates of patient population, pricing, and revenue opportunities may be inaccurate.
• The FDA could require approval of a companion diagnostic device, which could delay approval.
• The company faces substantial competition in the market.
• The company may not have sufficient cash to fund its contemplated operations.

Risks

• The market opportunity may be smaller than expected if the patient population is lower or if patients are not amenable to treatment.
• Regulatory authorities could require a companion diagnostic test, which could delay or prevent approval.
• The company may face delays in clinical trials or regulatory submissions.
• There is a risk that the product candidates may not receive regulatory approval or become commercially successful.
• The company may not be able to obtain adequate financing in the future.

Future Outlook

The company anticipates completing the NDA submission in the second half of 2024 and is planning to discuss a path forward for patients with KRAS wild-type disease with the FDA. They also expect to present the mature dataset from the RAMP 201 trial at a medical meeting in the second half of 2024.

Management Comments

• Dan Paterson, president and chief executive officer of Verastem Oncology, stated that the initiation of the rolling NDA submission is an important step towards addressing the significant unmet needs of patients with KRAS mutant low-grade serous ovarian cancer.
• Management believes that the avutometinib and defactinib combination has the potential to be a new standard of care in patients with recurrent low-grade serous ovarian cancer, if approved.

Industry Context

This announcement is significant as there are currently no FDA-approved treatments specifically for recurrent LGSOC, and the current standard of care treatments have demonstrated low response rates and high discontinuation rates due to adverse events. The development of avutometinib and defactinib combination could fill a critical unmet need in the treatment of this rare cancer.

Comparison to Industry Standards

• The current standard of care for LGSOC includes hormonal therapy or chemotherapy, which have demonstrated an objective response rate (ORR) between 6-13% with discontinuation due to adverse events of 17-30%.
• The RAMP 201 trial showed a 27% ORR in all patients, 37% in KRAS mutant LGSOC, and 15% in KRAS wild-type LGSOC, suggesting a potential improvement over existing treatments.
• The MILO study, a relevant comparator, showed a 13% ORR and a 10.6 month median progression free survival (PFS) with standard of care, while the RAMP 201 trial showed a 60% clinical benefit rate at 6 months.
• The FRAME study, a previous trial of the combination, showed a 42% ORR and a median duration of response of 26.9 months, indicating the potential for durable responses.

Stakeholder Impact

• Shareholders may see a positive impact due to the potential for a new revenue stream.
• Patients with recurrent KRAS mutant LGSOC may benefit from a new treatment option.
• Healthcare providers may have a new tool to treat this rare cancer.
• Employees may benefit from the company's growth and success.

Next Steps

• Complete the NDA submission with mature data from the RAMP 201 trial in the second half of 2024.
• Discuss a path forward for patients with KRAS wild-type disease with the FDA.
• Present the mature dataset from RAMP 201 at a medical meeting in the second half of 2024.
• Continue enrollment in the RAMP 301 confirmatory Phase 3 trial.
• Continue development of other product candidates in the pipeline.

Key Dates

Keywords

avutometinib, defactinib, LGSOC, KRAS mutant, NDA, FDA, ovarian cancer, RAMP 201, Breakthrough Therapy Designation, Orphan Drug Designation