FDA provides path for accelerated approval of nomlabofusp for FA
Developer Larimar now expects regulatory submission by mid 2026
The U.S. Food and Drug Administration (FDA) has provided Larimar Therapeutics with clear expectations for an application seeking accelerated approval of nomlabofusp, its potentially disease-modifying therapy for Friedreich’s ataxia (FA), according to the drug developer.
Accelerated approval is a type of conditional approval based on early clinical data suggesting that a treatment is likely to benefit patients. It is granted by the FDA for drugs for serious conditions that fill an unmet medical need.
Among the FDA’s recommendations, per Larimar, is the creation of a database to monitor safety in a group of patients with at least six months of therapy exposure, mostly to the highest dose of nomlabofusp.
Because more time is needed to gather safety data for both adults and children with FA, the company has extended its timeline to submit the biologics license application (BLA) to the end of June next year, instead of the previously proposed target date of before the end of this year.
“We are thrilled to have clarity from [the] FDA on the safety database recommendations,” Carole Ben-Maimon, MD, president and CEO of Larimar, said in a company press release. Ben-Maimon noted that the agency’s response “[followed] submission of safety information included in a briefing package from our nomlabofusp program.”
Given those recommendations, and the company’s intention “to request approval to treat a broad population of patients including adults and children,” Ben-Maimon said Larimar now plans to “submit our BLA seeking accelerated approval in the second quarter of 2026.”
In FA, a deficiency in the protein frataxin disrupts the functioning of mitochondria, the source of most of a cell’s energy. Dysfunctional mitochondria primarily affect cells with high-energy demands, such as those in nerves and muscles, resulting in problems with muscle control and coordination, known medically as ataxia.
Nomlabofusp, previously known as CTI-1601, delivers a lab-made version of frataxin protein to patients’ cells and mitochondria. Administered by injections under the skin, or subcutaneously, its goal is to restore energy production and ease FA symptoms.
Nomlabofusp previously selected for START pilot program
The FDA selected nomlabofusp last year to participate in a pilot program dubbed START, for Support for Clinical Trials Advancing Rare Disease Therapeutics. This milestone-driven program aims to accelerate the development of new therapies addressing unmet medical needs for rare diseases by fostering enhanced communication with the agency.
“Our participation in the START program has been incredibly valuable and continues to help us expedite clinical and regulatory development for the nomlabofusp program,” Ben-Maimon said.
Nomlabofusp’s safety, tolerability, and pharmacological profile are being evaluated in a run-in study (NCT06681766), enrolling adolescent FA patients, ages 12-17, at a site in Maryland.
Dosing has been completed, and participants are now being screened for an ongoing open-label extension (NCT06447025). That OLE aims to assess treatment with 50 mg of nomlafobusp in patients who complete the run-in study, alongside adults from an earlier trial. An expansion to the OLE is planned to include patients who have never participated in any of Larimar’s clinical trials and have never received nomlabofusp.
In data reported last year, treatment with nomlafobusp led to sustained increases in skin frataxin levels, trends toward clinical improvement, and good tolerability for daily injections of 25 mg nomlafobusp for up to about 8.5 months.
Data from study’s long-term extension expected in September
Rusty Clayton, Larimar’s chief medical officer, noted in the release that the OLE “is further advancing, with some participants now on treatment for up to 15 months.” Per Clayton, that includes dosing at both 25 mg and 50 mg.
“The high adherence rates we are seeing for daily subcutaneous injections in participants over the long term is very encouraging,” Clayton said.
He added that the researchers “have begun transitioning adolescents from the [pharmacological] run-in study and have amended the protocol to include patients who have never participated in any of our prior clinical trials.”
According to Larimar, OLE data from 30 to 40 participants who received at least one dose of nomlabofusp, including those on the 50 mg dose, are expected to be reported in September. The results will include pharmacological data from 14 adolescents — some on placebo — in the run-in study.
The company is intending to seek accelerated approval of nomlabofusp based on early clinical data. If granted, Larimar would still need to conduct further testing to demonstrate the benefits of the therapy.
Nomlabofusp has the potential to be the first disease modifying therapy for FA and we look forward to expanding the clinical program to patients around the world with the initiation of our global Phase 3 study.
Based on discussions under the START program, the FDA recommended a database to evaluate safety in at least 30 participants with continuous study drug exposure for six months, with at least 10 patients exposed for one year. Most of the safety data will be from participants receiving the 50 mg dose.
The agency also agreed that skin levels of frataxin could be used as a surrogate outcome measure, thus acknowledging the data that shows frataxin levels in skin reflect those in nerves and muscles, according to the company. Whether higher skin frataxin is acceptable for accelerated approval will be determined at a future BLA review.
“We now have written recommendations from [the] FDA on critical elements of the BLA submission including the safety database as well as the use of skin frataxin (FXN) concentrations as a reasonably likely surrogate endpoint,” Ben-Maimon said.
As required by the FDA’s accelerated approval pathway, Larimar is planning a global Phase 3 clinical trial, expected to be underway at the time of BLA submission, to confirm the clinical benefits of nomlabofusp in FA patients. Activities are ongoing to identify and qualify sites in the U.S., Europe, Canada, and Australia.
“Nomlabofusp has the potential to be the first disease modifying therapy for FA and we look forward to expanding the clinical program to patients around the world with the initiation of our global Phase 3 study,” Ben-Maimon said.
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