News in Novartis’ year-end report recently announced the discontinuation of several programs, including the Huntington’s disease (HD) program, based on an evaluation of potential benefits and risks from the Phase 2b VIBRANT-HD trial (NCT05111249) Did.1 The study, which was temporarily interrupted in August 2022, evaluated its lead candidate branapram (LMI070).2
VIBRANT-HD was a double-blind, placebo-controlled trial that began in early 2022 and was expected to include 75 participants with early manifested HD. The core treatment period leading to screening and baseline assessment included a 17-week dose-ranging period followed by a 53-week blinded extension. The researchers used the percent reduction in mutant huntingtin (HTT) protein levels at the end of the 17-week treatment period as the primary endpoint.3
In the summer of 2021, Novartis decided to discontinue development of branapram, originally intended for children with spinal muscular atrophy, and focus its efforts on adults with HD. Data from HD animal models and early safety studies of branapram in healthy adults supported this decision.
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Currently, there are no approved disease-modifying therapies that delay the onset of HD or slow disease progression. In December 2021, the FDA granted the agent Priority Review designation to speed up the review process. Branapram, an investigational oral disease-modifying therapy, is an mRNA splicing modifier that targets the underlying pathophysiology of HD by modifying HTT mRNA throughout the brain and body, resulting in increased HTT protein levels. Decrease.Four
In recent years, the development of therapies for HD has been an ongoing challenge. In March 2021, another company, Wave Life Sciences, announced the discontinuation of two HD agents (WVE-120102 and WVE-120101) following early results from Phase 1b/2a trials.Five
Around the same time, Roche’s Tominersen was also discontinued, but this drug was the first to successfully target the mutant HTT protein and reduce its levels. He announced the design of a new phase 2 trial of the drug, with post-hoc analyzes showing it may benefit a subgroup of younger patients with a lower disease burden, he said.6