Treatment with pridopidine slowed clinical progression and maintained function, cognition, and motor performance in pre-defined analyses of a subgroup of early-stage Huntington’s disease (HD) patients who were not taking antidopaminergic medicines (ADMs). The PROOF-HD study did not meet its overall primary or secondary endpoints in the full population
In the group of patients who were not taking ADMs, pridopidine demonstrated clinically meaningful improvement from baseline for one year, and slowing of decline thereafter, as measured by cUHDRS
ADMs may cause side effects that cannot be distinguished from HD progression and can negatively impact clinical outcome measures and confound treatment-related effects in a clinical triali
This randomized, double-blind, placebo-controlled study represents the first Phase 3 trial in HD to deliver a consistent pattern of meaningful benefits across multiple outcome measures of efficacy including cognition (SWR) and motor function (Q-Motor), in a subgroup of subjects, as well as a favorable safety profile
A planned confirmatory study in early HD patients, designed to confirm pridopidine’s effects and support global regulatory approval pathway discussions, is expected to start next year
Prilenia Therapeutics B.V. and Ferrertoday announced the publication, in the journal Nature Medicine, of a manuscript entitled “Pridopidine in Early-Stage Manifest Huntington Disease: A Phase 3 Trial”ii. The publication describes data showing that treatment with pridopidine slowed clinical progression in Huntington’s disease (HD) patients not taking antidopaminergic medicines (ADMs).
The published data, from pre-defined analyses of a subgroup of patients not taking ADMs from pridopidine’s Phase 3 PROOF-HD trial, show that treatment with pridopidine achieved a clinically meaningful improvement from baseline for one year and slowing of decline thereafter, as measured by cUHDRS, with change vs placebo of 0.46, 0.45, 0.41 and 0.27 at 26, 39, 52 and 65 weeks (the end of the double-blind trial). Annual reductions in cUHDRS of 0.1–0.3 points have been associated with a clinically meaningful benefit in HDiii.
Importantly, the benefits in cUHDRS in this subgroup of subjects with HD were seen across domains of function, cognition, and motor performance. Pridopidine also achieved similar maintenance of cognition with no deterioration, as measured by Stroop Word Reading Test (SWR), and motor performance, as measured by Quantitative Motor (Q-Motor).
Ralf Reilmann, MD, FAAN, Founding Director, George Huntington Institute and publication lead author, said: “The published data represents the first Phase 3 HD trial to deliver consistent and meaningful benefits on progression across multiple clinical domains of HD such as function, cognition and motor performance, while also confirming pridopidine’s favorable safety and tolerability profile. Upcoming studies can now refine patient selection and account for the impact of ADM exposure, which obscured the true drug-related benefits. Appropriate stratification and dosage strategies will control for this confounding factor and allow demonstration of pridopidine’s positive treatment effects on clinical progression of symptoms. I would like to express my gratitude for the continued commitment of everyone working to support the next data-driven steps to making this well-tolerated and easily administered treatment option available to HD patients.”
Dina de Sousa, European Huntington Association (EHA) Board member, remarked:“We have no options to help slow down our decline. Nothing to help people feed themselves a little longer, button a shirt a little longer, walk a little longer, or maybe even dance a little longer. Treatment options are needed now that can enable maintenance of independence for as long as possible. These results provide hope that there are therapies that can go further than just symptom control, and hope that we can take a step forward toward availability of a disease-modifying treatment able to slow down the inexorable march of this dreadful disease.”
“These data provide a clear path forward for next year’s planned global confirmatory study in early HD patients, aimed at confirming pridopidine’s effect and supporting ongoing global regulatory discussions,” said Dr. Michael R. Hayden, CEO of Prilenia.
“Nature Medicine is one of the world’s leading peer-reviewed medical journals, and this important publication adds to the weight of evidence in support of the sigma-1 receptor agonist approach and the development of pridopidine for the treatment of neurodegenerative diseases such as HD and ALS,” said Oscar Pérez, Chief Scientific Officer at Ferrer.
