Last patient visit completed in Phase 3 PROOF-HD trial of pridopidine

Prilenia working on top-line data, expected in coming months

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The last patient has completed the final visit in the Phase 3 PROOF-HD trial testing oral pridopidine for Huntington’s disease.

That means that the study’s main placebo-controlled part is done, according to Prilenia Therapeutics, pridopidine’s developer, which sponsored the nearly 18-month-long trial.

Now, the first data are expected in the coming months — and nearly all participants (98%) have opted to continue in the trial’s ongoing open-label extension phase, in which all are receiving the experimental therapy.

“There is an urgent need for treatments that can alter the course of [Huntington’s disease] and bring hope to individuals and families impacted by the disease,”  Michael R. Hayden, PhD, CEO and founder of Prilenia, said in a company press release, adding, “Our team is working diligently to bring top-line results to the community as quickly as possible.”

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PROOF-HD is being conducted in collaboration with the Huntington Study Group, a cooperative therapeutic research organization focused on the neurodegenerative disease. Prilenia noted in its statement that the study “was completed on time and as planned,” and said the top-line results “in early Q2 2023.”

“We thank the Huntington Study Group and their partners, study investigators, and most importantly study participants and their families for their contribution to this important research,” Hayden said.

Pridopidine, originally developed by Teva Pharmaceuticals, is a highly selective activator of the sigma-1 receptor (S1R) protein, which is found in the brain and spinal cord. The protein plays a role in nerve cell function and survival.

Specifically, S1R activation stimulates production of brain-derived neurotrophic factor, a protein with neuroprotective effects that is found at lower than normal levels in Huntington’s patients.

As such, pridopidine is expected to protect against nerve cell death and slow disease progression for people with Huntington’s or other neurodegenerative diseases.

The experimental oral therapy holds orphan drug status for the treatment of Huntington’s in the U.S. and the European Union, and fast track designation in the U.S. Both designations are intended to help speed pridopidine’s development toward approval by providing financial and regulatory support.

Data from the earlier Phase 2 PRIDE-HD trial (NCT02006472) showed that a year of twice-daily pridopidine treatment, at a dose of 45 mg, significantly prevented functional declines relative to a placebo among 400 patients with early-stage Huntington’s.

Findings from the Phase 2 OPEN-HART trial (NCT01306929) then supported the long-term benefits of pridopidine, with five years of treatment being linked to a significantly slower functional decline compared with a placebo in a separate Huntington’s trial (NCT00608881).

Based on these promising results, Prilenia launched the Phase 3 PROOF-HD trial (NCT04556656), which is evaluating pridopidine’s safety and efficacy against a placebo in adults, ages 25 and older, with early-stage Huntington’s disease.

It finished enrolling a total of 499 patients at more than 50 sites in North America and Europe in November 2021. Participants were randomly assigned to receive an oral capsule of either pridopidine (45 mg) or a placebo, twice daily for up to 78 weeks, or nearly 1.5 years.

PROOF-HD’s main goal is to evaluate the therapy’s ability to preserve patients’ functional abilities, as assessed by the Unified Huntington’s Disease Rating Scale–Total Functional Capacity, after 65 weeks, or about 16 months.

Our team is working diligently to bring top-line results to the community as quickly as possible.

According to Prilenia, PROOF-HD is the only late-stage clinical study in Huntington’s disease that is assessing a therapy’s ability to slow disease progression as a goal.

In addition to Huntington’s, Prilenia is also evaluating the potential of pridopidine as a treatment for a number of other neurodegenerative and neurodevelopmental conditions, with the next most advanced program that of amyotrophic lateral sclerosis.