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FDA Updates: Clinical Hold on Rapport's RAP-219 for DPNP, Phase 2 Trial for Mivelsiran in CAA, and Review of Ataluren Resubmission

• The FDA has placed a clinical hold on Rapport Therapeutics' RAP-219 IND application for diabetic peripheral neuropathic pain (DPNP) due to protocol design concerns. • A phase 2 trial (cAPPricorn-1) will evaluate Alnylam's mivelsiran, an RNAi therapeutic targeting APP, for cerebral amyloid angiopathy (CAA) in a 200-patient global study. • The FDA has accepted PTC Therapeutics' resubmitted NDA for ataluren to treat nonsense mutation Duchenne muscular dystrophy (nmDMD), with no PDUFA date set.

The FDA has issued a clinical hold on Rapport Therapeutics' investigational new drug (IND) application for RAP-219, a potential treatment for diabetic peripheral neuropathic pain (DPNP). The agency is requesting additional information and amendments to the trial's protocol design. Rapport Therapeutics is addressing the FDA's concerns and will provide updates on the phase 2a trial initiation timeline as available. This hold does not affect other RAP-219 studies, including the ongoing phase 2a trial for focal epilepsy and a planned trial for bipolar disorder.
A new phase 2 study, cAPPricorn-1 (NCT069393712), will investigate mivelsiran (Alnylam Pharmaceuticals) for cerebral amyloid angiopathy (CAA). Mivelsiran is an intrathecally administered RNAi therapeutic that targets amyloid precursor protein (APP). The global study aims to enroll 200 patients across North America, Europe, and Australia. Patients will be randomized 1:1 to either intrathecal mivelsiran or placebo for a 24-month double-blind period, followed by an optional 18-month open-label extension. The primary endpoint is the annualized rate of new lobar cerebral microbleeds. The study includes patients with sporadic CAA (aged ≥50 years with probable CAA per Boston Criteria Version 2.0) or Dutch-type CAA (aged ≥30 years with a known E693Q APP variant).
The FDA has accepted PTC Therapeutics' resubmitted new drug application (NDA) for ataluren (Translarna) to treat boys with nonsense mutation Duchenne muscular dystrophy (nmDMD). The resubmission follows a complete response letter (CRL) issued several years ago. The FDA is not obligated to follow PDUFA review timelines and has not provided an action date. The NDA is based on data from the phase 3 Study 041 (NCT03179631), which included 359 patients with nmDMD, and analyses from the STRIDE registry, an observational study of ataluren's safety and effectiveness in routine care. Ataluren is currently licensed in multiple countries, including the European Union and Brazil.
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Reference News

[1]
FDA Places Hold on RAP-219, cAPPricorn-1 Study to Assess Mivelsiran in CAA, FDA ...
neurologylive.com · Nov 9, 2024

FDA places clinical hold on Rapport Therapeutics' phase 2a trial for RAP-219 in diabetic peripheral neuropathic pain; Al...

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