Novartis suspends dosing in phase 2b Huntington's trial after side effects reported

After seeing signs of side effects in some participants, Novartis has suspended dosing in its phase 2b Huntington’s disease trial assessing branaplam.

The trial's independent data monitoring committee recommended the suspension after a planned review unearthed findings that suggested possible side effects, according to an Aug. 24 update (PDF) from the Big Pharma. Specifically, the review found that branaplam may cause peripheral neuropathy, which is the result of nerve injury outside the brain and spinal cord.  

Early signs of side effects were observed in some participants, according to Novartis, though the number of patients experiencing this side effect was not divulged. The phase 2b trial, dubbed VIBRANT-HD, is a placebo-controlled study that aimed to recruit 75 patients. The trial had previously stopped enrolling patients, and it's unclear how many trial participants were dosed with branaplam.

Novartis will still move ahead with planned assessments of existing VIBRANT-HD data. The company will continue to gather more information over the next few months to determine next steps. VIBRANT-HD's aim was to determine the correct branaplam dosing needed to lower mutant huntingtin protein levels in the cerebrospinal fluid of adults with Huntington's disease.

Branaplam is an orally administered mRNA splicing modulator with an FDA fast-track designation in Huntington's. The small-molecule drug was initially designed to treat spinal muscular atrophy (SMA), though Novartis diverted its research after several setbacks.

In 2016, the company paused enrollment for its SMA trial assessing branaplam when animal models running parallel to the trial showed injuries to the peripheral nerves, spinal cord, testes and blood vessels in the kidney. After modifying the trial design and switching up dosing levels, Novartis resumed the program in Europe in 2017. However, in 2021, the company ended up ditching the effort altogether after branaplam showed underwhelming efficacy against SMA, stating that the decision was made as the result of recent advancements in the SMA treatment landscape.

In Novartis’ Aug. 24 letter—which was addressed to the Huntington’s disease community—the company acknowledged the difficult nature of the news, particularly for those who are part of the study.  The rare, genetic brain disorder progressively breaks down nerve cells in the brain and impacts emotions, motor ability and cognitive skills. There are no treatments to change the course of disease, though certain medications can reduce some symptoms. 

The dosing suspension comes on the heels of a layoff announcement. In June, the Swiss company revealed its plan to cut 8,000 jobs with the goal to save $1 billion. And just earlier this week, the company revealed that up to half of the 1,400 jobs cuts in Switzerland will be leadership positions.