8-K: Clene Inc. Receives FDA Guidance for Accelerated Approval Pathway of CNM-Au8 in ALS Treatment

Clene Inc. announced that the FDA has provided a potential path for accelerated approval of its drug CNM-Au8 for ALS, based on additional biomarker data.

Summary

• Clene Inc. has received guidance from the FDA regarding a potential accelerated approval pathway for its drug CNM-Au8 in the treatment of amyotrophic lateral sclerosis (ALS).
• The FDA recommends that Clene leverage additional Neurofilament Light (NfL) data from its Expanded Access Protocols (EAPs) and the HEALEY ALS Platform Trial.
• Clene plans to complete the additional NfL biomarker collection and analyses during the second quarter of 2025.
• The company intends to submit a New Drug Application (NDA) in mid-2025, following the incorporation of the EAP NfL biomarker analyses.
• Clene also plans to commence a confirmatory Phase 3 trial (RESTORE-ALS) before the NDA submission.
• The FDA will review whether NfL can serve as a surrogate endpoint for the effects of CNM-Au8 in ALS and if the magnitude of change observed on NfL is likely to predict clinical benefit.
• Clene presented data at the November 1, 2024 FDA meeting showing a 78% risk reduction in time to death during the open label extension of the HEALEY ALS Platform Trial.
• Data also showed an 83% risk reduction of time to death or PAV in CNM-Au8 participants with the highest baseline NfL and an 84% risk reduction in participants with baseline NfL median.
• Additionally, 91% risk reduction in time to death or PAV was observed in participants with any level of NfL decline at week 24.
• Long-term survival data from compassionate-use protocols showed a 31% risk reduction in CNM-Au8 participants compared to matched controls.
• Over 700 patient years of CNM-Au8 use have not identified any significant safety concerns.

Sentiment

Score: 8

Explanation: The document is very positive due to the FDA's guidance on a potential accelerated approval pathway and the strong clinical data presented. The company has a clear path forward and the results are encouraging.

Positives

• The FDA's guidance provides a clear path for potential accelerated approval of CNM-Au8.
• The use of EAP data could expedite the approval process.
• The company has demonstrated significant risk reductions in time to death and PAV in various analyses.
• The long-term survival data from compassionate-use protocols is encouraging.
• CNM-Au8 has shown a benign safety profile with no significant safety concerns identified.

Negatives

• The FDA will need to review whether NfL can serve as a surrogate endpoint for the effects of CNM-Au8.
• The magnitude of change observed on NfL must be shown to predict clinical benefit for ALS.
• The additional NfL biomarker collection and analyses are not yet complete and are planned for the second quarter of 2025.
• The NDA submission is not expected until mid-2025.

Risks

• The FDA may not ultimately accept NfL as a surrogate endpoint.
• The additional biomarker data may not be sufficient to support accelerated approval.
• The Phase 3 trial may not confirm the efficacy of CNM-Au8.
• There are risks associated with the timing of clinical trials and the submission of an NDA.
• The company's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates is a risk.

Future Outlook

Clene plans to submit an NDA for CNM-Au8 in mid-2025 and commence a confirmatory Phase 3 trial before the NDA submission. The company will continue to work with the FDA to finalize the statistical analysis plan for the EAP NfL biomarker analyses.

Management Comments

• Rob Etherington, President and CEO of Clene, stated that they are grateful for the FDA's willingness to consider how the available data from their expanded access programs may support the existing clinical study data.
• Jinsy A. Andrews, MD, MSc, FAAN, expressed gratitude that the FDA has recognized the power of real-world experience for a drug in ALS.
• Merit Cudkowicz, MD, stated that she was pleased to assist Clene in these varied supportive analyses.

Industry Context

This announcement is significant in the context of the limited therapeutic options available for ALS and the high sense of urgency to find effective treatments. The FDA's willingness to consider EAP data for accelerated approval is a positive development for the ALS community.

Comparison to Industry Standards

• The use of NfL as a biomarker is becoming increasingly common in neurodegenerative disease research, but its acceptance as a surrogate endpoint for regulatory approval is still evolving.
• The 78% risk reduction in time to death observed in the open label extension is a strong result compared to other ALS treatments.
• The 31% risk reduction in long-term survival from compassionate-use protocols is also a positive signal, especially given the advanced disease severity of the participants.
• Other companies developing ALS treatments include Biogen with Tofersen, and Amylyx Pharmaceuticals with Relyvrio, both of which have faced regulatory hurdles and have had mixed results in clinical trials.
• Clene's approach of using EAP data to support accelerated approval is a novel strategy that could potentially expedite the availability of a new treatment for ALS.

Stakeholder Impact

• Shareholders may react positively to the news of a potential accelerated approval pathway.
• Patients with ALS and their families may have increased hope for a new treatment option.
• Employees of Clene may be motivated by the progress of CNM-Au8.
• The medical community may be encouraged by the potential for a new treatment for ALS.

Next Steps

• Clene will complete additional NfL biomarker collection and analyses during the second quarter of 2025.
• Clene will meet with the FDA in early 2025 to review and finalize its statistical analysis plan for the EAP NfL biomarker analyses.
• Clene plans to submit a New Drug Application (NDA) in mid-2025.
• Clene plans to commence the confirmatory Phase 3 trial (RESTORE-ALS) before the NDA submission.

Key Dates

Keywords

ALS, CNM-Au8, FDA, Accelerated Approval, Neurofilament Light, Biomarker, Clinical Trial, NDA, EAP, Survival