PTC Runs into Latest Huntington's Roadblock with US Trial Pause (Updated)

A Phase II trial studying PTC Therapeutics’ PTC518 in Huntington's disease (HD) has been paused in the United States following a request from the FDA for additional data, the company announced Tuesday afternoon.

Enrollment for the 12-month PIVOT-HD trial will continue in several European countries and in Australia, according to PTC.

In a press release, the company stated there “have been no treatment-related adverse events” reported in or outside of the U.S.

In the U.S., the FDA has requested additional data to support the dosing and duration proposed in the 12-month study, Jeanine Clemente, senior director, U.S. & global corporate communications told BioSpace in an e-mail. 

"We are working with the FDA to determine the data that can address their concerns which could include clinical data from patients being treated in the ongoing PIVOT-HD study outside of the U.S.," Clemente said. 

When asked about the nature of the data requested, an FDA spokesperson told BioSpace the regulatory agency is "generally unable to discuss existing or potential applications" due to the confidentiality of that commercial information.

The global PTC518 trial consists of one placebo-controlled 12-week period that focuses on pharmacology and pharmacodynamic effects, followed by a 9-month placebo-controlled period where blood, CSF and radiographic biomarker data is collected and studied.  

PTC518 is an oral, small molecule splicing modifier that was specifically designed to selectively lower huntingtin mRNA and proteins. 

Huntington’s Space Hit Hard in 2022

As of today, there are no approved targeted therapies for Huntington's disease, and the research into such therapies has been cut from many companies' research and development plans for a number of reasons. 

Pittsburgh-based NeuBase announced a strategic restructuring last week that will see the company halting development and regulatory activities for its HD program. NeuBase simultaneously announced a 60% attrition of its total workforce.

On September 27, Exicure also restructured in a way that will impact Huntington's research. The company suspended ongoing programs with Ipsen and AbbVie after entering into a $1 billion partnership just last year for the treatment of Angelman syndrome and HD.

In August, Novartis halted its dosing in an ongoing Phase IIb VIBRANT-HD trial of branaplam in HD due to the discovery of possible side effects, including peripheral neuropathy, or nerve pain. 

There are still ongoing studies into other therapeutic options for HD, however.

Wave Life Sciences presented promising data in September from a Phase Ib/IIa SELECT-HD trial of WVE-003 that indicated target engagement and evidence of biomarker improvements. That trial is being conducted in 23 locations, not including the U.S., according to clinicaltrials.gov. The study is expected to extend to U.S. locations during Phase III of the trial.

On the preclinical front, bit.bio launched its Huntington's Disease cell model, which it stated will accelerate drug discovery and screening for affected patients. The model works by introduing a consistent, scalable model that replicates Huntington's disease in vitro. 

HD-related chorea may soon be treated with valbenazine from Neurocrine Biosciences, according to information released in April. Neurocrine saw positive results from a Phase III KINECT-HD study that evaluated the efficacy of valbenazine.

The drug is used to treat tardive dyskinesia, a disorder similar to HD that affects the nervous system and causes repetitive, involuntary muscle movements in the face, neck, arms and legs.