SKY-0515 Shows Significant HTT Reduction, AMT-130 Slows Huntington Progression, Capricor to Meet With FDA on CAP-1002

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

Newly announced data from Parts A and B of a phase 1 clinical trial showed that treatment with investigational SKY-0515 (Skyhawk Therapeutics) resulted in significant reduction of mutant huntingtin (HTT) mRNA in healthy volunteers. Given these positive topline results, the company anticipates dosing in Part C of the study, which includes patients with Huntington disease (HD), in Q3 2024 and initiation of a phase 2 study early next year. After 14 days of treatment with SKY-0515, patients in the 9 mg daily group in Part B of the study, otherwise known as the multiple-ascending dose (MAD) cohort, demonstrated an average HTT mRNA reduction of 72%. Less pronounced effects were seen in the lower dosed groups, with reductions of 41% and 19% in the 3 mg and 1 mg groups, respectively. For context, those on placebo saw average HTT mRNA increases of 2% throughout the study.

A new interim update to the ongoing phase 1/2 trials (NCT0543017; NCT04120493) assessing uniQure’s investigational gene therapy AMT-130 showed that treatment with high doses of the agent resulted in significant slowing of disease progression and lowering of neurofilament light (NfL) in patients with Huntington disease (HD). In the second half of 2024, the company expects to hold a Type B, multi-disciplinary meeting with the FDA to present these updated data and discuss potential expedited clinical development pathways and accelerated approval. The interim data update included 21 patients (low-dose: n = 12; high-dose: n = 9) who had 24-month follow-up data as of the March 31, 2024, cut-off date. After 24 months of treatment, those on high-dose AMT-130 demonstrated mean changes of –0.2 on composite Unified Huntington’s Disease Rating Scale (cUHDRS) compared with changes of –1.0 for an expanded, propensity-weighted external control group (n = 154). All told, this represented an 80% slowing of disease progression (P = .007).

According to a recent announcement, Capricor Therapeutics announced it will host a pre-biologics license application (BLA) meeting with the FDA over the coming months to discuss options to expedite a BLA filing for its investigational agent CAP-1002 as a therapy for Duchenne muscular dystrophy (DMD). The decision comes as the company reported positive 3-year data from the open-label extension (OLE) of its phase 2 HOPE-2 trial (NCT03406780). Following the completion of the double-blind, placebo-controlled portion of HOPE-2, eligible patients who wished to remain on treatment entered the OLE where they received CAP-1002, also known as deramiocel, at 150 million cells per infusion every 3 months. At 3 years from the start of the OLE study, patients with DMD on the active therapy (n = 12) showed a –4.1-point change in performance of upper limb (PUL v2.0), the primary end point, compared with changes of –7.8 for an external comparator (n = 32; delta change, +3.7 points; P <.001).

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