Following clearance by the US drug regulatory body the Food and Drug Administration (FDA) in July 2023, the pharmaceutical company Larimar Therapeutics has completed full enrolment and dosing of the 50 mg cohort in their US Phase 2 dose exploration trial of the drug CTI-1601 (nomlabofusp) for Friedreich’s ataxia (FA). CTI-1601 is a protein replacement therapy designed to deliver frataxin protein to the cells of people with FA. Frataxin proteins are decreased in those with FA. This phase of the trial will involve a daily dose of 50 mg of CTI-1601 for the first 14 days and then every other day until day 28, and it includes 15 participants. There were no reported serious adverse effects in either the CTI-1601 or placebo groups during the dosing period.
This progress comes after data from the completed 25 mg cohort indicated that CTI-1601 was generally well tolerated and showed increases in frataxin protein levels from baseline compared to placebo at day 14 (the final day of daily dosing in the trial). The company hope to release further data on the both the 50 mg and 25 mg cohorts, including safety information, in the first quarter of 2024.
The FDA has also given approval for Larimar Therapeutics to begin an open label extension trial with a 25 mg daily dose of CTI-1601 for 28 days in the first quarter of 2024. Open label extension trials are those that take place after randomised drug trials if results show the drug is found to have potential benefit. This open label trial will look at the long-term effects of CTI-1601. Larimar Therapeutics plan to use the findings from the 50 mg dose exploration trial to inform the dose and dosing regimen for the open label trial.
You can read the full press release from Larimar Therapeutics here. To receive more updates about the trials and their results, sign up to our e-newsletter here and follow our ‘Research news’ section on the Ataxia UK website here.
Update 12th February 2024:
On 12th February 2024, Larimar Therapeutics announced positive topline results from their phase 2 dose-exploration study in both the 25mg and 50mg cohorts. CTI-1601 was generally well tolerated following repeated subcutaneous injections in patients in the 25 and 50 mg cohorts with no serious adverse events. Dose dependent increases in frataxin levels were observed in skin and buccal cells (cells in the cheeks and lips). At Day 14, all patients with quantifiable levels of FXN at baseline and Day 14 treated with 50 mg of CTI-1601 achieved FXN levels in skin cells greater than 33% of the average level found in healthy volunteers, and 3 of the patients achieved levels greater than 50% of the average healthy volunteer level.
To read more about the topline results, view the press release here.
Update 20th May 2024:
On 20th May 2024, Larimar announced that the US drug regulator, the Food and Drug Administration (FDA) has removed their partial clinical hold on Larimar’s CTI-1601 clinical trial programme for FA. This is after in 2021, the FDA imposed a full clinical hold on the programme due to safety concerns, as higher doses of CTI-1601 had caused deaths in preclinical studies with non-human primates. And in 2022, the FDA lifted the full clinical hold, but maintained a partial clinical hold, limiting trials to the 25mg dose.
On May 30th 2024, Larimar announced that the FDA has selected their CTI-1601 programme to be a part of the FDA START pilot programme. START is a new milestone-driven programme designed to accelerate development of new therapies intended to address an unmet medical need for rare diseases.
CTI-1601 was selected based on potential for clinical benefit in a rare neurodegenerative disease, and demonstrated development programme readiness. The START pilot programme is intended to improve development efficiency through enhanced communication with the FDA. CTI-2601 is expected to be one of six total programmes selected by the FDA.
Read more in the press release here.
