Novartis has temporarily suspended dosing in a mid-stage study of an experimental Huntington’s disease drug, writing Wednesday in a letter to patients that its treatment was linked to nerve damage.
Investigators overseeing the study recommended halting treatment after “early signs” of peripheral neuropathy were reported in some participants at a planned data review.
The Phase 2 clinical trial was designed to enroll 75 patients with an early form of inherited neurological disease and give them one of four different doses of the drug, called branaplam, or placebo.
Researchers stopped drug dosing early this month, according to an update posted Aug. 8 on the website HDBuzz by Leora Fox, an assistant director of research and patient engagement at the Huntington’s Disease Society of America. Novartis’ announcement Wednesday was a “community update” following up on news of the suspension.
Fox, in her update, said the decision to halt treatment was based on evidence from neurological exams, assessments of patient symptoms and measurements of a protein known as neurofilament light protein that’s associated with nerve damage.
“It might be that the drug is really not safe for people with [Huntington’s], and moving forward isn’t an option,” she wrote on Aug. 8. “On the other hand, it might be possible to use lower or less frequent dosing, or it could be that branaplam may have affected some participants differently than others.”
Study researchers will continue to gather data as planned before the dosing suspension, a Novartis spokesperson said in an Aug. 24 email to BioPharma Dive. Any decision to restart treatment with the experimental drug, including at higher dose levels, will be made after consulting with the data monitoring committee and the trial’s leadership panel, the spokesperson added.
Branaplam is one of the most advanced experimental drugs aimed at changing the course of Huntington’s disease, which progresses over time and is characterized by uncontrolled movement and loss of cognitive function. In December, the Food and Drug Administration granted branaplam a Breakthrough Therapy designation, which is meant to accelerate development and review of promising new medicines for serious diseases. Novartis has, as recently as July, marked branaplam as a potential top-selling product.
In addition to assessing safety, the trial was meant to assess whether branaplam reduces the amount of a mutated form of the huntingtin protein, which is a biological marker of the disease. Although the technologies used vary, it’s an approach shared by other drug developers targeting the disease, including Roche, UniQure, PTC Therapeutics and Wave Life Sciences.
Roche and Wave hit setbacks in clinical testing that have raised questions about their medicines, however. Roche is pressing on with plans to run another trial, while Wave shelved two of its drugs in March 2021 and is now testing another. PTC expects to have three-month data from a mid-stage study of its drug by the end of this year, while UniQure recently revealed preliminary results for the first four patients treated with its gene therapy.
Research is urgent, as Huntington’s disease patients are in need of better treatment options. Currently, doctors can only treat the involuntary movements called “chorea” that patients experience or the psychiatric disorders associated with the condition.
Novartis had previously planned to advance branaplam in spinal muscular atrophy, but stopped that effort because it said the recent introduction of three drugs for the neuromuscular disorder made it difficult to enroll patients in a Phase 3 trial.