8-K: Chimerix Plans NDA Submission for Dordaviprone, Targets 2025 Approval

Chimerix is set to submit a New Drug Application (NDA) for dordaviprone (ONC201) by the end of 2024, seeking accelerated approval for recurrent H3 K27M-mutant diffuse glioma, with a potential PDUFA action date in Q3 2025.

Summary

• Chimerix plans to submit an NDA for dordaviprone (ONC201) for the treatment of recurrent H3 K27M-mutant diffuse glioma before the end of 2024.
• The submission follows extensive discussions with the FDA and includes data from a 50-patient primary efficacy analysis showing a 28% objective response rate using RANO 2.0 criteria.
• The company will request Priority Review, which could lead to a potential PDUFA action date in the third quarter of 2025.
• Dordaviprone has received Rare Pediatric Disease Designation and the company intends to apply for a Rare Pediatric Disease Priority Review Voucher.
• If the voucher is sold, 50% of the net proceeds will be paid to former Oncoceutics securityholders.
• Chimerix also expects to determine the recommended dosing for Phase 2 trials of ONC206 by early 2025.
• ONC206 is a second-generation drug showing monotherapy anti-cancer activity in preclinical models and is currently in dose-escalation clinical trials.

Sentiment

Score: 8

Explanation: The document is highly positive due to the planned NDA submission, promising clinical data, and potential for accelerated approval. The company also has a strong cash position and a clear path forward for its pipeline.

Positives

• Dordaviprone has shown a 28% objective response rate in a Phase 2 study using RANO 2.0 criteria.
• The median duration of response for dordaviprone was 10.4 months.
• Dordaviprone has a favorable safety profile with most treatment-related adverse events being mild and transient.
• The company has a substantial enrollment in the Phase 3 ACTION study for dordaviprone.
• ONC206 has shown monotherapy activity in multiple preclinical models and is progressing through dose escalation trials.
• Chimerix has a strong commercial platform expected to be ready for launch by Q3 2025, if the NDA is granted.
• Dordaviprone has patent protection through 2037, with potential for additional U.S. patent term extension.

Negatives

• The median overall survival from recurrence for H3 K27M-mutant diffuse glioma is approximately 5.1 months without treatment.
• There are no currently approved therapies for H3 K27M-mutant glioma.
• The company is reliant on the FDA granting priority review and accelerated approval for dordaviprone.
• The company is reliant on the success of the Phase 3 ACTION study for dordaviprone.
• There is a risk that the FDA may not accept the additional supportive data submitted in the NDA filing.

Risks

• The company faces risks related to obtaining and maintaining accelerated approval, priority review, and a rare pediatric disease priority review voucher.
• There is uncertainty regarding the FDA's response to the additional supportive data submitted in the NDA, including RANO 2.0 assessments.
• The timing, completion, and outcome of the Phase 3 ACTION study of dordaviprone are uncertain.
• There are risks associated with repeating positive results from prior studies in future studies.
• The clinical development of ONC206 carries inherent risks.
• Market acceptance of dordaviprone is not guaranteed.
• The company's cash runway and market conditions could impact results.

Future Outlook

The company anticipates a potential accelerated approval for dordaviprone in Q3 2025, and expects to determine the recommended dosing for Phase 2 trials of ONC206 by early 2025. They also plan to continue the Phase 3 ACTION study and explore international market opportunities.

Management Comments

• The company believes extensive program progress supports the New Drug Application seeking U.S. FDA accelerated approval.
• The company is positioned to accelerate growth from internal and/or external innovation.

Industry Context

This announcement is significant as there are currently no approved therapies for recurrent H3 K27M-mutant diffuse glioma, a highly aggressive and lethal form of cancer. The potential approval of dordaviprone would address a critical unmet medical need in the neuro-oncology space.

Comparison to Industry Standards

• The 28% objective response rate for dordaviprone using RANO 2.0 criteria is promising compared to the typical outcomes for recurrent high-grade gliomas, where response rates to standard therapies are often lower.
• The median duration of response of 10.4 months is also notable, as many treatments for recurrent gliomas offer only short-term benefits.
• The company is seeking accelerated approval, which is a common pathway for drugs targeting rare and serious diseases with unmet needs, similar to other orphan drug approvals in the oncology space.
• The use of a Rare Pediatric Disease Priority Review Voucher is a strategy employed by other companies in the rare disease space to expedite the review process and potentially generate revenue through the sale of the voucher.

Related Party Transactions

• 50% of the net proceeds from the sale of a Rare Pediatric Disease Priority Review Voucher would be payable to the former securityholders of Oncoceutics, Inc.

Stakeholder Impact

• Shareholders may see a positive impact from the potential approval of dordaviprone and the progress of ONC206.
• Patients with H3 K27M-mutant diffuse glioma could benefit from a new treatment option.
• Employees may experience growth opportunities as the company advances its pipeline.
• The company's success could lead to increased revenue and potential partnerships.

Next Steps

• Submit the NDA for dordaviprone to the FDA before the end of 2024.
• Request Priority Review for the NDA.
• Determine the recommended dosing for Phase 2 trials of ONC206 by early 2025.
• Continue enrollment in the Phase 3 ACTION study for dordaviprone.
• Prepare for the potential commercial launch of dordaviprone in Q3 2025.

Key Dates

Keywords

dordaviprone, ONC201, ONC206, H3 K27M-mutant glioma, NDA, accelerated approval, priority review, rare pediatric disease, ClpP agonist, DRD2 antagonist, brain tumor, clinical trial, PDUFA, imipridone