A Biohaven Pharmaceuticals drug developed to treat disease by modulating a neurotransmitter that’s important to normal brain function has failed a pivotal study in a rare neuromuscular disorder, marking the product candidate’s third clinical trial failure in as many indications in the past two years.
The latest disappointing data are from a test in spinocerebellar ataxia, an inherited disorder that leads to problems with muscle coordination, balance, movement, and speech. Symptoms of the neurodegenerative disorder begin in adulthood and cause progressively worsening muscle control that eventually leads to patients needing a wheelchair.
Spinocerebellar ataxia has three types, none of which have any FDA approved treatments. Biohaven said Monday that across all types of spinocerebellar ataxia, preliminary data show that the drug, troriluzole, did not beat a placebo according to a scale used to assess muscle control and movement. The New Haven, Connecticut-based biotech attributed the result to less than expected disease progression over the course of the study.
Despite the Phase 3 failure, Biohaven said an analysis of the unblinded data suggest a treatment effect in patients with spinocerebellar ataxia type 3, which is the most common form of the disorder. This group represented 41% of the participants in the 213-patient study. In this group, Biohaven said scores showed numerical improvement compared to a placebo. Given the unmet patient need in this disease, Biohaven said that it plans to take these results to the FDA to see if there is a path forward for the drug,
In a research note sent to investors Monday, William Blair analyst Tim Lugo wrote that while the FDA may allow some flexibility for rare diseases such as spinocerebellar ataxia, the firm will wait for additional updates before placing any value to the program. He added that investors had low expectations for troriluzole, and its latest failure will be viewed as a “clearing event,” meaning that it clears the way for the company to focus its energies elsewhere.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Troriluzole is designed to reduce levels of glutamate, a neurotransmitter. Dysfunction of this brain chemical is associated with a range of disorders including amyotrophic lateral sclerosis, Alzheimer’s disease, and obsessive compulsive disorder. The Biohaven drug is intended to increase activity of amino acids that clear glutamate from synapses.
So far, troriluzole hasn’t been successful in clinical trials. In 2020, Biohaven reported that the drug failed a Phase 3 study in generalized anxiety disorder. Last year, the company reported a Phase 2/3 failure in Alzheimer’s disease. The glutamate-clearing drug has one more shot. A Phase 3 clinical trial in obsessive compulsive disorder is still underway. In its report of first quarter 2022 financial results, the company said enrollment in this study is expected to be complete in the second half of this year.
Biohaven is in the process of being acquired by Pfizer in an $11.6 billion deal. The transaction is focused on the commercialized migraine drug Nurtec ODT, as well as other compounds that address the same protein target for pain. Pfizer is not getting the rest of the Biohaven neuroscience drug pipeline, which will be spun out as a separate, publicly traded company that will keep the Biohaven name. Troriluzole is among the programs that will be spun out as part of new Biohaven. Verdiperstat is the next most advanced program in the pipeline; preliminary data from a Phase 3 study in ALS are expected in the second half of this year. Last year, verdiperstat failed a Phase 3 clinical trial testing the small molecule in multiple system atrophy.
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