Developer kicks off accelerated approval process for FA drug
Several US sites are still recruiting people for nomlabofusp trial
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Larimar Therapeutics has begun the process of asking the U.S. Food and Drug Administration (FDA) to grant accelerated approval to nomlabofusp, its protein replacement therapy for Friedreich’s ataxia (FA).
Typically, drug developers seeking a therapy’s approval need to finish the entire application before submitting it to the FDA. But the FDA has granted Larimar permission for a rolling submission, meaning the company can submit each section of the application as soon as it’s ready, rather than waiting for the whole thing to be completed.
Larimar announced in late June that it had formally submitted the first piece of the rolling application. The rest of the application is expected to be submitted over the second half of 2026, according to a company press release.
The FDA’s accelerated approval pathway allows a therapy to be brought to market based on early data suggesting it will likely benefit patients, while requiring developers to run additional testing to definitively prove clinical benefit.
In this case, Larimar is asking the FDA to grant accelerated approval to nomlabofusp based on clinical data showing that the therapy boosts levels of the frataxin protein in patients’ cells. FA is caused by mutations that lead to low frataxin levels, and nomlabofusp is designed to deliver a working version of the protein.
The FDA has confirmed that it is willing to consider frataxin levels as a surrogate endpoint suggesting likely clinical benefit, Larimar noted. The company recently published animal data showing that increased frataxin levels in easily accessible skin cells are indicative of increased protein levels in other parts of the body.
Updated study findings suggest nomlabofusp increases frataxin levels
Larimar’s application is expected to be based mainly on data from an ongoing open-label study (NCT06447025) that’s testing nomlabofusp in FA patients ages 2 to 60. All participants in the trial are given the experimental therapy daily via subcutaneous (under-the-skin) injection. The trial is still recruiting participants at a half-dozen sites across the U.S.
According to newly shared data from Larimar, a total of 43 adolescent and adult participants in the open-label study have received at least one injection of nomlabofusp. Among them, 22 are still in the study while the other 21 have discontinued. Ten of the patients who discontinued experienced anaphylaxis (a severe allergic reaction). In all those cases, the patients returned to their usual state after receiving standard allergy treatments. There were also six patients who discontinued due to hives or other side effects, while another five withdrew for unspecified reasons.
Larimar said the most common side effects seen with nomlabofusp have been reactions at the injection site. These have mostly been nonserious and decreased in frequency over time. None of the injection site reactions led to patients discontinuing.
In line with previously reported data, updated findings from the study suggest that nomlabofusp is increasing frataxin levels in patients’ cells, as intended. Among 20 patients with three months of treatment data available, 50% achieved frataxin levels within the range typically seen in FA carriers (that is, people who do not have FA but carry a disease-causing mutation that they may pass to biological children).
All nine evaluable patients who have been on therapy for a year or more had frataxin levels within the range that’s seen in carriers, as did all three individuals who have been on treatment for 18 months.
Larimar preparing for Phase 3 trial to further test therapy
Available data also show that, after a year on nomlabofusp, scores on two standardized measures of disease severity have tended to improve — a marked contrast from the typical progression of FA, where disease severity gets worse over time. Measures of hand dexterity and fatigue showed improvement over the course of a year on nomlabofusp. Most of these measures showed continual signs of improvement out to 18 months in the small number of patients who have been on the treatment for that long.
“We continue to see improvements in multiple clinical outcome measures reinforcing the positive benefit-risk profile of nomlabofusp,” said Rusty Clayton, Larimar’s chief medical officer. “Collectively, sustained elevations in skin [frataxin protein] concentrations with concomitant directional improvements in key clinical outcomes relative to a FA natural reference population, along with a well-characterized safety profile, support the potential of nomlabofusp to meaningfully alter the course of this devastating disease.”
Marshall Summar, MD, the CEO of Uncommon Cures, one of the sites conducting the open-label trial, added: “The data generated to date suggest that nomlabofusp has the potential to meaningfully impact the underlying biology of the disease and translate into clinically relevant benefits. The clinical improvements observed so far are promising and mark a meaningful step toward what could become the first disease-modifying therapy for a patient population with significant unmet medical needs.”
In addition to the ongoing open-label study, Larimar is currently making preparations for a Phase 3 trial to further test the therapy. The company hopes the Phase 3 trial will confirm nomlabofusp’s clinical benefit, potentially supporting a transition from accelerated approval to full, traditional approval in the future.
“With compelling and consistent [open-label] study data in hand, rolling [application] submission initiated, and dosing of the first patient in our global confirmatory Phase 3 study approaching, we are executing on all fronts to bring what could be the first disease-modifying therapy to pediatric and adult patients living with FA,” said Carole Ben-Maimon, MD, Larimar’s president and CEO.
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