Tucked into its latest earnings report, Novartis confirmed to investors that it has stopped developing an experimental drug for Huntington’s disease.
The reason, according to Novartis, was an “overall assessment of the risk-benefit profile” observed in a mid-stage clinical trial named VIBRANT-HD. In August, Novartis said it had temporarily suspended dosing in the study, after discovering that some patients treated with the drug, known as branaplam, were experiencing nerve damage.
The confirmation in Novartis’ earnings comes a little less than two months after the company issued to members of the Huntington’s patient community a letter, in which it shared the “difficult news” that the branaplam program was being discontinued. The letter noted how new data were showing many, though not all, of the study participants who received branaplam demonstrated signs or symptoms of nerve damage.
Novartis also wrote that its decision was endorsed by the study’s steering committee as well as a group of independent experts who had been regularly reviewing the unblinded data.
Huntington’s is a rare disorder in which nerves cells progressively break down, making it increasingly difficult to move, think and function. It’s caused by mutations in the gene responsible for producing the “huntingtin” protein. There is currently no cure for Huntington’s, though doctors and patients do have a small assortment of drugs they can use to help alleviate the involuntary movements and psychiatric disorders associated with the disease.
As one of the few experimental Huntington’s drugs to advance to the later stages of clinical development, branaplam has garnered attention over the last few years.
While its function isn’t entirely understood, branaplam works on messenger RNA — the genetic instructions cells use to create proteins. Specifically, it appears to lower the amount of mutant huntingtin in the spinal fluid of Huntington’s patients.
In its December letter, Novartis wrote that VIBRANT-HD found mutant huntingtin levels decreased in branaplam-treated patients. Yet, with the safety concerns in mind, the company also concluded it would be “very unlikely that lower doses or different dose timings would be safe, and lower [the mutant protein] sufficiently to slow disease progression.”
Novartis had previously been evaluating branaplam as a potential medicine for another rare disease of the nervous system, spinal muscular atrophy, but stopped that work in mid-2021 due to “rapid advancements” in the treatment of SMA. By that time, there were three marketed drugs for SMA: Biogen’s Spinraza, Roche’s oral option Evrysdi, and Novartis’ own gene therapy, Zolgensma.
With branaplam officially sidelined, the slim crop of Huntington’s drugs in advanced testing becomes even slimmer.
Sage Therapeutics is currently running a trio of studies — two in Phase 2, one in Phase 3 — to assess the safety and effectiveness of its experimental treatment SAGE-718. And Roche just began enrolling a mid-stage study of its drug tominersen, with a goal of recruiting around 360 participants whose Huntington’s is in the early stages. That medicine, however, was unsuccessful in a Phase 3 study that read out results in 2021.
PTC Therapeutics, meanwhile, expects to have initial data from its own mid-stage trial in March.
The Dutch biotechnology company UniQure has also attracted attention with AMT-130, a potential gene therapy for Huntington’s. The therapy has already shown positive effects on mutant huntingtin levels in a handful of patients, though it has also elicited safety concerns.