FDA Places Hold on RAP-219, cAPPricorn-1 Study to Assess Mivelsiran in CAA, FDA Accepts Resubmitted NDA for Ataluren

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

According to a new announcement, the FDA has placed a clinical hold on Rapport Therapeutics’ submitted investigational new drug (IND) application for the initiation of a phase 2a proof-of-concept trial assessing RAP-219, an investigational therapy for epilepsy, as a potential treatment of patients with diabetic peripheral neuropathic pain (DPNP).The agency has requested the company to provide additional information and amendments specific to the protocol design of the trial. Rapport noted in the announcement that it believes in its ability to resolve this request and will offer an update on the expected timing of the phase 2a trial initiation once obtainable. This clinical hold is specific to the IND for DPNP and did not impact the company’s other studies assessing RAP-219, such as in the ongoing phase 2a trial for focal epilepsy or planned proof-of-concept trial for bipolar disorder.

A new phase 2 study, dubbed cAPPricorn-1 (NCT069393712), will assess the therapeutic potential of mivelsiran (Alnylam Pharmaceuticals), an intrathecally administered RNAi therapeutic targeting amyloid precursor protein (APP), in patients with cerebral amyloid angiopathy (CAA). The global study is currently aiming to enroll 200 patients across sites in North America, Europe, and Australia.The design of the trial was presented at the 2024 Clinical Trials on Alzheimer’s Disease (CTAD) conference, held October 29 to November 1, in Madrid, Spain. In cAPPricorn, patients are randomly assigned 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 study, which will include 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) will use annualized rate of new lobar cerebral microbleeds as the primary end point.

According to an announcement, the FDA has accepted PTC Therapeutics resubmitted new drug application (NDA) for its protein restoration therapy ataluren (Translarna) for the treatment of boys with nonsense mutation Duchenne muscular dystrophy (nmDMD). Because this was an NDA resubmission following a complete response letter (CRL) filed several years ago, the FDA is not obligated to follow PDUFA review timelines and thus, did not provide an action date for the therapy.The resubmitted NDA was based on data from a phase 3 placebo-controlled trial, dubbed Study 041 (NCT03179631), which included an intent-to-treat population of 359 patients with nmDMD. In addition, the resubmission also included analyses from the STRIDE registry, an ongoing, multicenter, observational study of the safety and effectiveness of ataluren in routine care. Currently, the therapy is licensed in multiple countries, including the European Union and Brazil.

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