Phase 2 Trial Shows Increased Frataxin Levels in Friedreich Ataxia Following CT-1601 Treatment


Positive data from the 25 mg cohort study exploring Larimar Therapeutics’ CTI-1601 has been submitted to the FDA, with a meeting scheduled with the agency later this quarter to discuss steps for a phase 2 trial.

Carole Ben-Maimon, MD, president and chief executive officer of Larimar

Carole Ben-Maimon, MD

Preliminary top-line data from Larimar Therapeutics’ phase 2, placebo-controlled, dose exploration trial (NCT05579691) investigating CTI-1601 in participants with Friedreich ataxia (FA) indicated that doses of 25 mg was safe, with observed increases in frataxin (FXN) levels compared with placebo in all evaluated tissues at day 14.1 These findings suggest that CTI-1601, a recombinant fusion protein intended to deliver human FXN to the mitochondria of patients with FA who are unable to produce enough of the essential protein, is well tolerated in patients.

Participants (n = 13) were randomized to receive either subcutaneous injections of 25 mg CTI-1601 (n = 9) or placebo (n = 4) daily for 14 days, followed by every other day injections until 28 days. On day 14, a median placebo-adjusted increase from baseline was observed in FXN levels in skin tissue (3.5 pg/µg) and buccal cells (0.9 pg/µg). Among 7 CTI-1601-treated participants, all demonstrated increases in skin FXN concentrations and 5 had increases in buccal cell FXN concentrations. In comparison, there were no increases in FXN concentrations observed in the skin tissue among the 4 participants on placebo and no increases in buccal cells in the 2 participants on placebo at the end of day 14.

“Our preliminary phase 2 data provide the first clinical indication that a 25 mg dose of CTI-1601 can increase frataxin levels in peripheral tissues, building upon our proof-of-concept phase 1 results,” Carole Ben-Maimon, MD, president and chief executive officer of Larimar said in a statement.1 “Importantly, the frataxin increases achieved with a relatively low 25 mg dose in our phase 2 trial suggest a continuous daily dosing regimen is preferred for maintaining increases achieved with 25 mg CTI-1601. I would like to thank all those who participated in our trials and look forward to our upcoming meeting with the FDA later this quarter.”

In a similar noninterventional study measuring FXN levels in 60 homozygous healthy volunteers, investigators reported median FXN concentrations of 16 pg/µg in skin and 8 pg/µg in buccal cells. Combined, the phase 2 data and a noninterventional study findings supported phase 1 data that demonstrated dose-dependent increases in FXN levels in peripheral tissue with daily dosing of 50 and 100 mg of CTI-1601 for at least 7 days, and no indemnified increase in FXN levels with daily dosing of 25 mg of CTI-1601 for only 4 days.

The company estimated that phenotypically healthy heterozygous carriers of the gene causing FA had median FXN concentrations of approximately 8 pg/µg in the skin and 4 pg/µg in buccal cells. This estimation was based on prior published research that indicates heterozygous carriers have levels of FXN that are approximately 50% of those of homozygous healthy patients.1

Data from the pharmacokinetic analysis of the phase 2 trial suggests that a steady state was achieved by day 14, last day of daily dosing. The safety data showed that the therapy was generally well tolerated with no serious adverse events and no important medical events reported. There was 1 severe adverse event reported, which was an allergic reaction to therapy which was resolved with standard treatment, and this participant withdrew from the trial. Notably, there was at least one injection site reaction, which ranged from mild to moderate, observed in 2 of 4 placebo-treated participants and, in all CTI-1601 treated participants.

“Our phase 2 results add to our safety database indicating that CTI-1601 is generally well tolerated. Thirty-seven adults with FA have been dosed with CTI-1601 across our phase 1 and 2 trials, with 35 completing treatment, one withdrawing due to an allergic reaction, and another withdrawing after a single 50 mg dose in the multiple ascending dose trial due to mild to moderate nausea and vomiting. We believe the safety, pharmacokinetic, and pharmacodynamic data generated to date support evaluation of a 50 mg dose of CTI-1601 in our phase 2 trial and look forward to discussing our findings with the FDA at our meeting later this quarter,” Ben-Maimon said in a statement.1

1. Larimar Therapeutics Reports Preliminary Top-line Data from Phase 2 Trial’s 25 mg Cohort Showing Increases in Frataxin Levels in Patients with Friedreich’s Ataxia and First Quarter 2023 Financial Results. News Release. Larimar Therapeutics. Published May 15, 2023. Accessed August 2, 2023.
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