Larimar Therapeutics is advancing nomlabofusp (CTI-1601) as a promising therapeutic candidate for Friedreich's ataxia (FRDA), a rare genetic disease characterized by frataxin deficiency. The company presented initial positive results from early clinical trials, outlining its clinical strategy, including plans for FDA approval via the START Pilot Program.
Mechanism of Action
Nomlabofusp is designed to correct the frataxin deficiency observed in FRDA patients. This recombinant fusion protein facilitates mitochondrial uptake, enabling the delivery of functional human frataxin protein. It incorporates a cell-penetrating peptide and a specific cleavage site for mitochondrial processing peptidase, ensuring targeted delivery and processing within the mitochondria.
Clinical Trial Data
Larimar's Phase 1 study involved double-blind, placebo-controlled single and multiple ascending dose trials. The study included 55 FRDA patients, with 28 in the single ascending dose trial and 27 in the multiple ascending dose trial. The primary endpoints focused on safety and tolerability. Secondary endpoints included pharmacokinetic, pharmacodynamic, and frataxin level assessments.
A Phase 2 dose exploration trial evaluated 25-mg and 50-mg doses over a 28-day treatment period in both ambulatory and nonambulatory FRDA patients who were either treatment-naïve or had prior exposure to nomlabofusp in a Larimar study. Results indicated dose-dependent increases in frataxin levels, with the 50-mg group exhibiting the most notable improvement.
Ongoing Open-Label Extension Study
Larimar has initiated an ongoing open-label extension (OLE) study, with the first patient dosed in March 2024. This study will enroll both adolescent and children, with adolescent patients participating in a pharmacokinetic run-in study before OLE enrollment. Key objectives include assessing clinical efficacy, frataxin concentrations, and long-term pharmacokinetic data. Preliminary data from the OLE study is anticipated in the fourth quarter of 2024.
Regulatory Strategy and Market Context
Larimar intends to pursue accelerated approval, targeting a BLA submission by mid-2025. Currently, Skyclarys (omaveloxolone) is the only FDA-approved treatment for FRDA, which functions by activating the Nrf2 pathway involved in cellular response to oxidative stress. Nomlabofusp stands out as the only protein replacement product in the FRDA pipeline, offering a distinct approach to addressing the underlying frataxin deficiency.
