Larimar's lead candidate still in limbo as company preps FDA response and maybe a new trial, too

It’s been well over a year since the FDA slapped a hold on Larimar Therapeutics’ only clinical asset. Now, after a meeting with the agency, the biotech is preparing to submit a full response, including plans for a phase 2 trial of the drug at a lower dose.

The therapy, CTI-1601, is a recombinant fusion protein intended to deliver human frataxin into the mitochondria of patients with Friedreich’s ataxia, an autosomal-recessive genetic disease that causes difficulty walking, a loss of sensation in the arms and legs, and impaired speech that worsens over time and usually starts in childhood.

The FDA, which previously gave the therapy a fast-track tag, halted the trial program in May 2021 after Larimar sent off data showing a number of deaths that occurred at the highest dose levels in a nonhuman primate toxicology study.

The agency requested more information in February 2022, as the company remained optimistic about a path forward toward resolving the hold.

Larimar has now received feedback from a recent meeting with the FDA to discuss the hold, and the company plans to submit a complete response in the third quarter. The biotech also proposed a four-week phase 2 trial to collect data on extending the lower dose of CTI-1601 as well as to explore whether lower doses for longer periods can safely increase frataxin levels.

Larimar CEO Carole Ben-Maimon, M.D., said the company believes its complete response to the FDA will enable CTI-1601’s return to the clinic.

“The proposed study has been designed to provide additional information on CTI-1601’s safety profile as well as pharmacokinetic and pharmacodynamic profiles, which we believe will allow us to select appropriate doses for future long-term dosing,” Ben-Maimon said in an Aug. 11 statement. “It will also enable us to build on our prior phase 1 results, which provided clinical proof-of-concept for CTI-1601 by demonstrating its ability to increase frataxin levels in peripheral tissues.”

Data from phase 1 single- and multiple-ascending dose clinical trials had previously indicated that daily subcutaneous injections of doses of up to 100 mg of CTI-1601 for up to 13 days were generally well tolerated, the company said. No serious adverse events were reported from the early-stage trial, Larimar pointed out.

Despite the freeze on its only asset, Larimar has cash and securities of $54.9 million, which it estimates will last through the third quarter of 2023.