Three years after the U.S. Food and Drug Administration (FDA) first placed a full clinical hold on Larimar Therapeutics’ Phase 2 clinical study, the hold has officially been lifted. The study centers around nomlabofusp, a recombinant fusion protein designed to treat Friedreich’s ataxia. So far, available data suggests that nomlabofusp increases frataxin levels in buccal cells; Larimar Therapeutics hopes that frataxin expression in tissues could be used as a surrogate endpoint when the company eventually pursues accelerated approval of this therapy.

Friedreich’s ataxia, a rare genetic disorder, results from FXN gene mutations that prevent the body from creating enough frataxin. Frataxin is a protein that plays a role in mitochondrial health and function. In Friedreich’s ataxia, the gene mutation and resulting frataxin deficiency cause multiple neurological and movement difficulties such as poor coordination, hearing and vision problems, slurred or impaired speech, fatigue, and foot abnormalities (among others). Friedreich’s ataxia can be fatal, especially with a weakening heart muscle and resulting heart disease. While Skyclarys is approved to slow disease progression, it is not able to halt the disease. Additional research and development are needed to provide patients with options.

Friedreich’s Ataxia Program Clinical Hold

Within the Phase 2 open-label extension study, Larimar Therapeutics was evaluating varying nomlabofusp doses ranging from 25mg to 100mg in patients with Friedreich’s ataxia. But the trial was halted in May 2021, reports Annalee Armstrong in FierceBiotech, after the FDA placed a full clinical hold. This means that Larimar Therapeutics had to halt and suspend the clinical work being done in its trial. 

The FDA chose to enact a full clinical hold after reviewing data from a nonhuman primate toxicology study done on nomlabofusp. Although up to 100mg nomlabofusp was given in the human studies with no problematic safety indications or serious adverse reactions, the nonhuman primate toxicology study did show potential issues. At the highest doses, multiple nonhuman primates died. 

After the submission of new data and a deeper evaluation of existing data, the full clinical hold was changed to a partial clinical hold in September 2022. Larimar Therapeutics was given the OK to dose participants with 25mg nomlabofusp. Higher doses would be considered following the submission of additional data. 

This led to the FDA finally lifting its clinical hold and allowing patients to be dosed with 50mg nomlabofusp. At this point in time, dosing up to 100mg is not allowed without FDA authorization and data to support its safety.