A Promising Candidate for Friedreich's Ataxia

This past August, Larimar Therapeutics delivered a presentation highlighting their drug candidate, nomlabofusp (CTI-1601), positive initial early clinical trial results, and the company’s clinical strategy, including the FDA approval process and FDA START Pilot Program.

Nomlabofusp works by correcting the frataxin deficiency commonly observed in FRDA patients.The recombinant fusion protein is designed for mitochondrial uptake where frataxin is expressed. Nomlabofusp contains a specific cell-penetrating peptide and a specific cleavage site for mitochondrial processing peptidase, enabling the delivery of a functional human frataxin protein.

Larimar’s phase 1 study consisted of double-blind, placebo-controlled single and multiple ascending dose trials in patients with FRDA. There were 55 patients, 28 of whom were allotted to the single ascending dose trial and 27 of whom were allotted to the multiple ascending dose trial. Safety and tolerability were primary endpoints for both ascending dosing groups. Pharmacokinetic, pharmacodynamic, and frataxin levels were secondary endpoints.

A phase 2 dose exploration trial tested a 25-milligram (mg) and 50-mg dose over a 28-day treatment period on ambulatory and nonambulatory FRDA patients who were nomlabofusp treatment naïve or had previously participated in a Larimar study. Frataxin levels increased based on the dose administered to healthy volunteers, with the 50-mg group exhibiting the most improvement.

Larimar has undertaken an ongoing open-label extension (OLE) study, with the first enrolled patient being dosed in March 2024. Preliminary data is expected to be published in quarter four of 2024. The study will continue enrolling patients, including adolescents and children.Before enrolling in the OLE study, the adolescent patients will first participate in a pharmacokinetic run-in study.Clinical efficacy, frataxin concentrations, and long-term pharmacokinetic data are some of the key study objectives.

The company intends to pursue accelerated approval with a targeted BLA submission by the middle of net year.

Currently, Skyclarys (omaveloxolone) is the only treatment of FRDA that has bene approved by the FDA. Skyclarys have been shown to activate the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is involved in the cellular response to oxidative stress. Nomlabofusp is the only protein replacement product in the FRDA pipeline.