Prilenia Therapeutics is planning to file its Huntington’s disease therapy pridopidine in the EU, despite mixed results in a phase 3 trial.
Pridopidine is an oral agonist of the S1R protein, which is expressed in the brain and spinal cord and is thought to regulate several key processes that are impaired in neurodegenerative diseases like Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS), promoting nerve cell function and survival.
The filing, scheduled for mid-2024, sets up a possible approval of pridopidine in 2025, according to the Netherlands and US-based biotech.
In the pivotal PROOF-HD study reported last year, pridopidine failed to meet its primary endpoint of slowing functional decline in adults with HD compared to placebo over 65 weeks of follow-up, measured using the Unified Huntington Disease Rating Scale-Total Functional Capacity score (TFC). It was, however, able to show a benefit on this measure in a subgroup of patients who were not on other treatments used to manage symptoms.
Based on the result, Prilenia has speculated that the drug’s effect on the main endpoint was reduced by the use of neuroleptic medications and VMAT2 inhibitor drugs used to control the involuntary, jerky movements known as chorea, which both affect the dopamine pathway.
Crucially, the subgroup analysis was prespecified in the trial protocol, recognising the difficulty of enrolling HD patients who were not already taking medication, according to PROOF-HD’s lead North American investigator Andrew Feigin of NYU Grossman School of Medicine.
“PROOF-HD marks the first time in HD that we have had a study suggest benefit on multiple important clinical measures, including progression, cognition, and motor findings,” said Feigin when presenting the results at the 2023 American Academy of Neurology (AAN) annual congress.
At the moment, the only therapies for HD address the symptoms of the disease, and pridopidine is vying to become the first drug approved to slow down its clinical progression, offering a lifeline to the approximately 100,000 HD patients worldwide.
Prilenia’s chief executive, Michael Hayden, said the decision to move ahead with a filing followed “constructive discussions” with European regulators, adding that the company is also hoping to hold talks with the FDA about a potential route to market for pridopidine in the US.
Pridopidine, meanwhile, is also being developed for ALS, and in January Prilenia said it had completed discussions with regulatory agencies over the design of a single, pivotal phase 3 trial that could be used to support filings.
At last year’s AAN, the company presented initial results from the phase 2 HEALEY ALS study, showing that the drug was able to achieve significant improvements on several clinical outcome measures, including rate of progression, dyspnoea, speech decline, and quality of life in patients with early-stage ALS.
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