Larimar's Friedreich's ataxia program free at last from FDA hold

Larimar Therapeutics’ Friedreich’s ataxia program is free at last, with the FDA fully lifting a clinical hold that had remained in part on the program since 2021.

The rare disease biotech can now proceed with dosing 50 mg in a phase 2 open-label extension dose exploration study for nomlabofusp, previously known as CTI-1601, according to an after-market release Monday.

The drug is a recombinant fusion protein intended to deliver human frataxin into the mitochondria of patients with Friedreich’s ataxia. The autosomal recessive genetic disease causes difficulty walking, a loss of sensation in the arms and legs, and impaired speech that worsens over time and usually starts in childhood.

Trouble for Larimar began in May 2021, when the FDA placed a full clinical hold on the program after viewing data from a nonhuman primate toxicology study that showed multiple deaths occurred at the highest dose levels.

At that point, Larimar had already tested up to 100 mg in human patients in a phase 1 test, which revealed no serious adverse events, important medical events or treatment-related severe adverse events, according to a May 2021 press release.

The FDA lifted most of the hold in September 2022, leaving in place a partial hold restricting dosing to 25 mg until further data from that cohort were submitted to the agency.

That’s now been completed, and Larimar is free to proceed with the 50-mg cohort in the open-label extension. CEO Carole Ben-Maimon, M.D., said work will get underway after “further characterization of frataxin PD at the 25 mg dose.”

If Larimar wants to step above 50 mg, the company will have to seek the FDA’s blessing with additional data to support the increased dose. Interim data from the open label extension study are expected in the fourth quarter of this year.

Previously, a 50-mg dose in a multiple ascending dose trial showed that daily injections of nomlabofusp increased frataxin levels in the buccal cells of patients with Friedreich’s ataxia. This is a key biomarker of the disease and has been correlated with improved neurological function in patients.

William Blair analyst Myles Minter, Ph.D., said the 50-mg dose escalation has the potential to increase frataxin levels between 5% to 10% over baseline, which would be in line with key opinion leaders’ suggestions for a therapeutic threshold.

“Although we expected Larimar to be cleared to dose Friedreich’s ataxia patients with 50 mg nomlabofusp in the open label extension after the positive phase 2 data, the entire partial clinical hold removal is a nice surprise being reflected with the stock up 15% aftermarket,” Minter wrote in a Monday evening note.

The company’s shares opened Tuesday morning up 16% to $8.44, compared to $7.27 at close the day prior.

Larimar is also working with the FDA to be able to use tissue frataxin levels as a surrogate endpoint for accelerated approval, according to Minter. The company is targeting the second half of 2025 for a biologics license application for nomlabofusp. But Minter noted that Larimar has a few hurdles to clear before that’s possible, such as the inclusion of pediatric patients and the exact regulatory path.

“We view the use of frataxin biomarker data to support accelerated approval as rational, but we also believe a measure of clinical benefit may be needed,” Minter said.

William Blair expects nomlabofusp to launch in 2028, providing a differentiated option from Biogen’s Skyclarys. Larimar’s offering could also be used in addition to that therapy if safety data are developed.