EMA’s CHMP recommends against pridopidine’s Huntington’s approval
Therapy won fast track status in US, orphan drug designation in US, EU
A committee of the European Medicines Agency’s (EMA) has recommended that the experimental oral medication pridopidine not be approved for adults with Huntington’s disease.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) recommendation will be reviewed by the European Commission, which has final say over therapy approvals in the European Union (EU). The commission isn’t required to abide by CHMP’s recommendations, but almost always does.
“We are disappointed, but undeterred in our commitment to bring what we believe is an effective therapy to patients and will explore all options collaboratively with regulators,” Prilenia Therapeutics and Ferrer stated in a joint company press release.
Prilenia agreed with Ferrer this year to codevelop and commercialize the therapy in Europe and other markets outside North America, Japan, and the Asia Pacific region. The companies said they plan to launch a potentially registrational clinical trial to further test pridopidine’s safety and efficacy in people with Huntington’s. Registrational trials are designed to support future applications toward a therapy’s approval. Details on the trial’s design were not disclosed.
Huntington’s is a genetic disorder that causes certain nerve cells in the brain to sicken and die, resulting in a range of motor, cognitive, and behavioral symptoms.
Testing pridopidine
Pridopidine is an orally available small molecule that works by activating sigma-1 receptor, a protein that regulates cellular pathways essential for nerve cell function and survival that are often impaired in Huntington’s.
The therapy received orphan drug and fast track designations in the U.S., and orphan drug status in the EU for Huntington’s. The designations are meant to expedite a drug’s clinical development and regulatory review.
Pridopidine, which would be marketed in Europe as Nurzigma should it be approved, has been tested in several clinical trials.
A Phase 2 study called PRIDE-HD (NCT02006472) tested pridopidine (45 mg capsule, twice a day) against a placebo in more than 400 adults with Huntington’s, with data indicating it slowed the progression of functional decline.
The Phase 3 PROOF-HD trial (NCT04556656) then tested the same dose against a placebo in nearly 500 adults with early Huntington’s. The results showed no difference between the groups in terms of overall functional decline.
However, subgroup analyses indicated pridopidine-treated participants who weren’t taking antipsychotics and/or treatments for chorea (involuntary movements) saw slower disease progression, with benefits in motor and cognitive measures observed.
Based on these findings, Prilenia’s regulatory application sought pridopidine’s conditional approval in the EU for adults with early Huntington’s who aren’t being treated with those medications. Conditional approval lets an experimental therapy be marketed based on early clinical trial data that support its efficacy, but to win full approval, further trial results must confirm its benefits.
The EMA agreed to review the application last year and CHMP considered the available trial data weren’t enough to prove the therapy’s efficacy in early Huntington’s.
“The validity and relevance of the results of the analyses in the subgroup of patients (adults with early Huntington’s disease who were not treated with [antipsychotics and/or chorea medicines]) from the [PROOF-HD] study have not been demonstrated,” the agency wrote in its recommendation.
Prilenia and Ferrer now plan to launch a new global study of pridopidine to confirm its benefits in Huntington’s and its enrollment is “expected to start as soon as possible.” Pridopidine is also being tested for amyotrophic lateral sclerosis, another neurodegenerative disease, and a registrational Phase 3 trial is being prepared.
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