FDA Puts Hold on CTI-1601 Clinical Development

The U.S. Food and Drug Administration has put a hold on the clinical development of CTI-1601, an investigational treatment for Friedreich’s ataxia (FA) that is being developed by Larimar Therapeutics.

According to a press release from Larimar, the hold was put in place after Larimar notified the FDA of deaths that occurred at the highest dose levels in an ongoing 180-day toxicology study being conducted in non-human primates (NHPs, usually macaques or other species of monkeys that are biologically similar to humans).

The FDA stated it would need to review full data from the ongoing study before it would allow Larimar to initiate further clinical trials with human participants.

Larimar had planned to begin an open-label extension trial, called Jive, in which participants from previous clinical trials of the investigational therapy could continue treatment. It was expected to begin earlier this year.

The company also was planning to initiate a multiple-ascending dose (MAD) clinical trial to test the medication in children, similar to a previous Phase 1 MAD clinical trial (NCT04519567) that enrolled 27 adults with FA.

In that trial, participants were given subcutaneous (under-the-skin) injections of CTI-1601, at doses of 25, 50, or 100 mg, or a placebo for 13 days. Results showed the treatment was well-tolerated with no treatment-related serious adverse side effects reported, and that it increased frataxin levels in participants’ tissues.

Based in part on these trial results, the European Medicines Agency (EMA) last week granted the priority medicines (PRIME) designation to CTI-1601 for the treatment of FA.

PRIME designation is given to candidate therapies with promising clinical data showing a potential to treat diseases of high unmet medical need. It provides Larimar with enhanced interaction and early dialogue with the European regulatory agency, ultimately speeding the development and review of CTI-1601.

Carole Ben-Maimon, MD, Larimar’s president and CEO, said the FDA’s decision to impose a clinical hold was “disappointing,” but “it does not change our previously stated clinical development strategy for CTI-1601.”

“Patient safety is our top priority, and we will continue with our plan to complete the NHP toxicology study, assess the data, and discuss that data with FDA to obtain their consent prior to initiating our Jive and pediatric MAD trials,” Ben-Maimon said. “Based on all of the information we have regarding CTI-1601’s safety profile to date, we continue to believe there is a path forward toward the initiation of our Jive and pediatric MAD trials.”

However, because of the additional regulatory requirements that come with responding to a formal clinical hold, Ben-Maimon said beginning these trials may be delayed until next year.

FA is caused by mutations in the FXN gene, resulting in the production of a defective form of the protein frataxin, which normally is important for the health of mitochondria.

CTI-1601 is a modified form of the frataxin protein that was designed to enter the mitochondria, aiming to replace the defective protein in patients.