Dosing Paused in Phase 2 Branaplam Trial Due to Possible Side Effects

Branaplam's use in VIBRANT-HD study may be causing peripheral neuropathy

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Due to possible side effects, dosing is being paused in the Phase 2 VIBRANT-HD clinical trial of oral branaplam (LMI070) in adults with Huntington’s disease.

A scheduled assessment found “early signs” that “branaplam might be causing peripheral neuropathy,” a condition marked by pain or numbness in the extremities caused by damage to nerves outside the brain and spinal cord, Novartis, which is developing branaplam and sponsoring the trial, stated in a letter to the Huntington’s community.

“We know this is difficult news for the entire [Huntington’s disease] community, especially for those who are part of the ongoing study,” the company added. It noted that, while dosing is paused, clinical assessments of trial participants are continuing as planned.

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VIBRANT-HD testing branaplam in adults with early manifest disease

Branaplam was originally developed to treat spinal muscular atrophy (SMA), a genetic disorder characterized by the death of nerve cells that control movement. Experiments in preclinical models indicated that the therapy could lower levels of the toxic huntingtin protein that drives Huntington’s.

Novartis launched the global Phase 2 VIBRANT-HD clinical trial (NCT05111249) in December 2021 to test an optimal dose of branaplam in about 75 adults, ages 25 to 75, with early manifest Huntington’s. The study is evaluating doses of the therapy — 56 mg, 112 mg, and doses ranging from 28 mg to 154 mg, all given as an oral solution once a week — against placebo in three successive patient groups to determine that optimal dose.

VIBRANT-HD’s main goals are the treatment’s safety and tolerability, as well as its effect on mutant huntingtin protein in the fluid around patients’ brains after 17 weeks.

Like other clinical trials, VIBRANT-HD has an independent data monitoring committee — a group of outside experts tasked with reviewing unblinded data as the trial is ongoing, to ensure the safety of participants. The decision to pause dosing was based on a committee recommendation after a regularly planned data review showed that branaplam may be causing peripheral neuropathy as an unexpected side effect.

The trial’s steering committee, which includes medical professionals and members of the Huntington’s community, supported the decision to temporarily suspend dosing, the letter stated.

“The study was specifically designed with robust monitoring to detect early safety signals and to allow us to make informed decisions for the trial,” Novartis stated. “We will be gathering more data and information in the coming months to better understand these effects and decide on next steps.”

The U.S. Food and Drug Administration (FDA) granted branaplam orphan drug and fast track designations as a potential Huntington’s treatment.

“We wish to highlight how grateful we are to the people participating, and their families, and how important it is for those in the study to continue to be assessed. With this participation, the community will add to the body of knowledge about [Huntington’s disease], help continue progress toward new treatments, and assist us in making the best decisions regarding the future development of branaplam,” Novartis stated.