Clinical Trials

Date: 2018-06-04

Type of information: Treatment of the first patient

phase: 3

Announcement: update on patient enrollment

Company: Retrophin (USA - CA)

Product: RE-024 Fosmetpantotenate

Action mechanism:

RE-024 is a small molecule discovered by Retrophin that is being developed as a replacement therapy for phosphopantothenate. Preclinical studies in PANK-deficient animal models and cell lines have demonstrated the ability of RE-024 to restore Coenzyme A levels. PKAN is caused by a mutation in the PANK2 gene, which encodes a critical protein that metabolizes vitamin B5 (pantothenate) to phosphopantothenate. The disruption of this metabolic pathway ultimately leads to decreased levels of CoA, an important substrate for many functions such as mitochondrial energy metabolism. Clinical manifestations of PKAN include developmental delay in children, dystonia sometimes causing intractable pain, parkinsonism with Parkinson’s-like freezing and bradykinesia, choreoathetosis, status dystonicus, dysarthria, spasticity, rigidity, and dysphagia often leading to feeding tube placement.

Disease: pantothenate kinase-associated neurodegeneration (PKAN)

Therapeutic area: Rare diseases - Genetic diseases - Neurological diseases

Country:

Trial details:

The FORT (FOsmetpantotenate Replacement Therapy) Study is an international, randomized, double-blind, placebo-controlled study evaluating RE-024 for the treatment of PKAN. This Phase 3 clinical trial is designed to evaluate the safety and efficacy of RE-024 in approximately 82 patients with PKAN aged 6 to 65 years. The primary endpoint will be the change in score on the Pantothenate Kinase-Associated Neurodegeneration Activities of Daily Living (PKAN-ADL) scale, from baseline through 24 weeks of treatment. After completing the 24-week treatment period, all patients will be eligible to receive RE-024 as part of an open-label extension.
The PKAN-ADL is a novel, PKAN-specific, patient-reported outcome scale measuring motor abilities to function in daily living for patients with PKAN. The scale is an adaptation of Part II of the comprehensive and widely-referenced Unified Parkinson's Disease Rating Scale (UPDRS). For the purposes of this trial, the UPDRS was adapted to be optimally relevant to PKAN through a systematic revision involving experts, patient advocacy leaders and regulatory interaction.
The FORT Study is being conducted under a Special Protocol Assessment (SPA) agreement, which indicates concurrence by the FDA that the design of the pivotal trial can adequately support a New Drug Application (NDA) seeking U.S. approval of RE-024 for the treatment of PKAN.

Latest news:

• On June 4, 2018, Retrophin announced that the independent Data Monitoring Committee (DMC) for the pivotal Phase 3 FORT Study, which is evaluating fosmetpantotenate for the treatment of pantothenate kinase-associated neurodegeneration (PKAN), has completed its scheduled clinical safety review required to open enrollment for pediatric patients. Upon review of the available safety and tolerability data of fosmetpantotenate in adult patients with PKAN in the study to date, the DMC recommended that the pivotal trial continue as planned, and supported initiation of enrollment in pediatric patients aged 6 to 17.
Retrophin anticipates completion of patient enrollment around year-end 2018, and top-line data to become available in the second half of 2019.
• On July 25, 2017, Retrophin announced that the first patient has been dosed in the FORT (FOsmetpantotenate Replacement Therapy) Study, an international, registrational Phase 3 clinical trial assessing the safety and efficacy of RE-024 (fosmetpantotenate) for the treatment of pantothenate kinase-associated neurodegeneration (PKAN).