8-K: CervoMed Announces Positive Results from Phase 2b Clinical Study Extension of Neflamapimod in Dementia with Lewy Bodies

CervoMed reports positive results from the extension phase of its Phase 2b RewinD-LB study, showing that a new batch of neflamapimod capsules led to increased drug concentrations and significant improvements in patients with dementia with Lewy bodies (DLB).

Summary

• CervoMed announced positive results from the first 16 weeks of the extension phase of the Phase 2b RewinD-LB study of neflamapimod in the treatment of dementia with Lewy bodies (DLB).
• The new batch of neflamapimod capsules led to increased plasma drug concentrations and demonstrated improvement on the primary outcome measure, change from baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) (p<0.001 vs. old capsules; p=0.003 vs. placebo).
• Improvement was also demonstrated on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (CGIC) (p=0.035 against either old capsules or placebo).
• A lower incidence of falls was observed in participants receiving the new batch of capsules compared to either the old capsules or placebo during the extension phase.
• Of the 159 participants randomized in the initial phase, 149 entered the extension phase, during which all participants received neflamapimod.
• The change in CDR-SB was lower in the New Capsule group compared to the Old Capsule group (difference=-0.73, 95% CI: -1.14, -0.32; p<0.001) from the end of the initial phase through Week 16 of the Extension.
• When analyzed from baseline of the study overall through to Week 16 of the Extension, the New Capsules demonstrated a positive benefit compared to placebo (difference= -0.45, 95% CI: -0.78, -0.15; p=0.003).
• On CGIC, administration of the New Capsules led to an improved score (4.02 vs. 4.46 with Old Capsules, p=0.035).
• The incidence of falls was lower in participants who received New Capsules compared to those who received Old Capsules during the Extension (7.4% vs. 14.5% for all participants; 4.0% vs. 15.4%, p=0.025, for participants with screening plasma ptau181 < 2.2 pg/mL).
• The RewinD-LB study is funded by a $21.3 million grant from the National Institutes of Health's National Institute on Aging.

Sentiment

Score: 8

Explanation: The document presents positive clinical trial results, suggesting potential for a new treatment for DLB. However, the need for additional funding and regulatory approval introduces uncertainty.

Positives

• The new batch of neflamapimod capsules led to increased plasma drug concentrations.
• Significant improvements were observed in CDR-SB and CGIC scores.
• A lower incidence of falls was seen in participants receiving the new capsules.
• The drug was generally well tolerated, with no new safety signals identified.
• The results are similar to those seen in the Phase 2a clinical study.

Negatives

• The initial 16 weeks of the study failed, attributed to lower than expected plasma drug concentrations from the original capsules.
• The old capsules had inferior dissolution kinetics with extended aging.

Risks

• The company's future success depends on securing additional funding for Phase 3 trials.
• Clinical trial results may not be replicated in later studies.
• Regulatory approval of neflamapimod is not guaranteed.
• General economic, political, business, industry, and market conditions could impact the company.

Future Outlook

The company is planning to complete the full 32-weeks of the extension phase of the study and engage with regulatory authorities to discuss finalizing Phase 3 plans after additional data are available later this year.

Management Comments

• James E. Galvin, MD, MPH, stated that neflamapimod has the potential to fundamentally change the disease course of DLB and our approach to treating the disease.
• John Alam, MD, stated that the consistency and magnitude of the clinical effect of neflamapimod on the CDR-SB are similar to the Phase 2a study results and demonstrate proof-of-concept for neflamapimod as a potential treatment for dementia with Lewy bodies.
• John-Paul Taylor, MBBS(hons) MRCPsych PhD, stated that the results from the extension phase of the RewinD-LB study are highly persuasive and similar to what was seen in the Phase 2a clinical study.

Industry Context

DLB is the third most common degenerative disease of the brain, and there are currently no approved treatments in the U.S. for the management of DLB, making neflamapimod a potentially significant advancement if approved.

Comparison to Industry Standards

• The magnitude of effect seen on the CDR-SB in this study is described as rare in dementia clinical research.
• The current standard of care for DLB is cholinesterase inhibitor therapy, which is approved for use in AD, but in DLB patients typically improves cognition transiently, and does not impact the motor component of the disease.
• The treatment response in AscenD-LB in the participants who did not have AD co-pathology (as assessed by a blood biomarker, plasma ptau181) was substantial (effect size > 0.7) and greater than the overall study population.

Stakeholder Impact

• Positive results could lead to a new treatment option for DLB patients and their families.
• Successful development and approval of neflamapimod could benefit CervoMed's shareholders.
• The company's employees may benefit from the company's success.

Next Steps

• Complete the full 32-weeks of the extension phase of the study.
• Engage with regulatory authorities to discuss finalizing Phase 3 plans.
• Initiate Phase 3 study or other additional clinical trials evaluating neflamapimod in DLB.

Key Dates