RARE Daily

Fears of Neuronal Damage Cause Novartis to Suspend Dosing in Huntington’s Disease Trial

August 25, 2022

In a letter to the Huntington’s disease community, Novartis said it has temporarily halted dosing in the VIBRANT-HD phase 2b study of branaplam in adults with Huntington’s disease due to early signs of side effects in some participants that suggest it may cause peripheral neuropathy.

Peripheral neuropathy results from injury to the nerves located outside of the brain and spinal cord. The study steering committee endorsed the recommendation made following a regularly planned review by an independent Data Monitoring Committee, and temporarily suspended dosing. The DMC did not recommend terminating the study at this time.

“We would like to emphasize that the study is moving forward with planned assessments,” Novartis said in its letter to the HD community. “The study was specifically designed with robust monitoring to detect early safety signals and to allow us to make informed decisions for the trial. We will be gathering more data and information in the coming months to better understand these effects and decide on next steps.”

Huntington’s disease (HD) is a progressive disorder that causes brain cell (neuron) degeneration in certain areas of the brain. It is caused by mutations in the HTT gene and is inherited in an autosomal dominant manner. The defective gene codes for a protein called huntingtin, which in its defective form results in uncontrolled movements, loss of intellectual abilities, and emotional disturbances. Symptoms typically appear between the ages of 35 and 44 years. People with Huntington’s disease most often live for 15 to 18 years after the condition appears.

Branaplam is a small molecule that was originally developed by Novartis to treat spinal muscular atrophy. In late 2020 Novartis reported that branaplam lowers the level of huntingtin protein, and held promise as an attractive way to treat HD.

The Huntington’s community has seen several setbacks to the development of a treatment, which has been a stumbling block for many companies. In 2021, Roche said it was stopping dosing of its antisense candidate tominersen in a late-stage trial. This was followed by Wave Life Sciences dropping two earlier stage trials.

Author: Rare Daily Staff

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