AFFINITY DUCHENNE Trial Expands, Suvecaltamide Fails Phase 2b Study of Essential Tremor, PTC518 Shows Dose-Dependent Huntingtin Lowering

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

According to a recent announcement, REGENXBIO has initiated enrollment in a new cohort of patients aged 1-3 in its phase 1/2 AFFINITY DUCHENNE trial (NCT05693142) to assess the safety and efficacy of RGX-202, an investigational gene therapy, in boys with Duchenne muscular dystrophy (DMD). The company expects to announce initial strength and functional assessment data for both dose levels of the trial in the second half of 2024. The trial, a multicenter, open-label, dose escalation and dose expansion study, is now enrolling ambulatory boys with DMD aged 1 to 11, including 5 aged 1-3. Those younger, newly added patients will receive RGX-202 at the pivotal dose level (2 x 1014 genome copies/kg body weight). In addition, the company noted they it continues to enroll the remaining patients in the ages 4-11 cohort and expects to imminently complete the enrollment of up to 7 patients at dose level 2 early third quarter of 2024.

In a company update, Jazz Pharmaceuticals announced that its investigational agent suvecaltamide, otherwise known as JZP385, did not achieve its primary end point of statistical significance vs placebo in a phase 2b trial (NCT05122650) of adults with essential tremor. Designed as a highly selective and state-dependent modulator of T-type calcium channels, suvecaltamide will continue to be assessed in its ongoing phase 2 trial (NCT05642442) of Parkinson disease (PD) tremor, with results expected in the first quarter of 2025. The phase 2b study, a 12-week, multicenter, double-blind, randomized, placebo-controlled trial comprised of 420 participants from 4 countries, used change in the modified Essential Tremor Rating Assessment Scale (TETRAS) composite outcome score as the primary end point. Overall, the therapy failed to significantly distinguish itself from placebo on TETRAS; however, numeric improvements were observed with the active agent. Although not statistically significant, suvecaltamide-treated patients also showed numeric improvements over placebo on Clinical Global Impression-Severity (CGI-S) scale, a secondary end point.

New 12-month, interim data from the phase 2 PIVOT-HD study (NCT05358717) showed that treatment with PTC518 resulted in dose-dependent lowering of huntingtin (HTT) mRNA and protein levels in blood cells of patients with Huntington disease (HD). Overall, the investigational agent was considered safe and well tolerated, with treated patients achieving desired cerebrospinal fluid (CSF) exposure and stable neurofilament light (NfL) levels. In the 2-part study, patients were randomly assigned to doses of PTC518 at 5 (n = 10) or 10 mg (n = 12) or placebo (n = 10), for 12 weeks, followed by an additional 9-months to end of study. After 12 weeks, results showed a –30% decrease in HTT protein in the 10 mg group, –21% decrease in the 5 mg group, and +12% increase in those on placebo.

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