Nomlabofusp for Friedreich’s ataxia to be tested in children, teens
Larimar plans to launch study by year's end with patients ages 12-17
Larimar Therapeutics plans to launch a study by the end of the year that will test the pharmacological properties of its investigational therapy nomlabofusp, formerly CTI-1601, in children and adolescents, ages 2 to 17, with Friedreich’s ataxia (FA).
It will begin with the enrollment of 12-15 adolescent patients, ages 12-17, who will be randomly assigned to receive daily nomlabofusp or a placebo.
After completing this study, the participants can join an ongoing open-label extension (NCT06447025), or OLE, of a Phase 2 dose-escalation study in which they would receive daily nomlafobusp over the long term. All seven OLE sites, which span the U.S., are now open, according to the company.
“Our OLE study continues to progress with all seven sites now activated and interim data planned for the fourth quarter of this year,” Carole Ben-Maimon, MD, Larimar’s president and CEO, said in a company press release. “Expanding our clinical program into younger patients will allow us to evaluate the effect of nomlabofusp earlier in the disease process.”
The company also is planning a global confirmatory study to start by mid-2025, with potential sites in North America, Europe, and Australia. Data from the OLE and other completed studies will form the basis of a biologics license application (BLA) seeking the therapy’s accelerated approval in the U.S.
“We made significant achievements in our nomlabofusp program [in the second quarter of this year] that strongly position us for successful execution across important catalysts over the next 12 months,” Ben-Maimon said.
Larimar hopes START inclusion will aid in planned regulatory submission
In June, the U.S. Food and Drug Administration (FDA) selected nomlabofusp for the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program. This program aims to speed the development of new therapies for rare diseases through improved communication with the agency.
“We were honored to be selected by the FDA to participate in the START pilot program which may be invaluable in helping us achieve our timeline for BLA submission targeted for the second half of 2025 to support accelerated approval,” Ben-Maimon said. “We are actively pursuing clinical sites in the U.S., Europe, U.K., Canada, and Australia in anticipation of initiating a global confirmatory study in mid-2025.”
Larimar also entered an agreement with Friedreich’s Ataxia Research Alliance (FARA) to join the TRACK-FA Neuroimaging Consortium (NCT04349514). Through MRI scans, that natural history study will track brain and spinal cord changes in individuals with FA; it is collecting longitudinal data from large groups of patients.
As an industry partner, Larimar is funding the study, will contribute to its design and analysis, and will have access to all study data for use in its regulatory filings.
“We are excited to have recently joined the TRACK-FA Neuroimaging Consortium as an industry partner to support research to define disease-specific neuroimaging biomarkers for potential use in clinical trials,” Ben-Maimon said.
Nomlabofusp is lab-made version of missing FA protein
FA is caused by a deficiency in frataxin, a protein involved in the functioning of mitochondria, the source of most of a cell’s energy. As a result, cells with high-energy demands, such as nerves and muscles, are affected, leading to problems with muscle control and coordination, referred to as ataxia.
Nomlabofusp is a lab-made version of the frataxin protein that’s modified to allow it to move into cells and mitochondria. Its goal is to restore energy production and ease FA symptoms.
The Phase 2 dose-escalation study (NCT05579691) enrolled 28 adults with FA, with nomlabofusp administered as a subcutaneous or under-the-skin injection. Treatment was found to increase frataxin levels in skin cells in a dose-dependent manner.
The study’s ongoing OLE is assessing the therapy’s long-term safety and tolerability, its impact on frataxin levels in tissues, and its pharmacokinetic (PK) properties, or how the medicine moves into, through, and out of the body. Patients who participated in previous nomlabofusp clinical trials can enter the OLE.
We plan to initiate a [pharmacokinetic properties] run-in study in adolescents with Friedreich’s ataxia (FA) by year-end, with [the] option for study participants to transition to the OLE study after completing the run-in study.
A planned study also will assess the pharmacokinetic properties of nomlabofusp in adolescents with FA.
“We plan to initiate a PK run-in study in adolescents with Friedreich’s ataxia (FA) by year-end, with [the] option for study participants to transition to the OLE study after completing the run-in study,” Ben-Maimon said.
OLE participants will receive 25 mg daily doses given by patients themselves or their caregivers, with plans to increase the dose to 50 mg. Data will be compared with those from an external control group from the FARA-sponsored FA Clinical Outcome Measures Study (NCT03090789), launched in 2001, which is following the natural history of FA in patients.
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