FA treatment nomlabofusp picked for FDA’s START pilot program

Effort was launched in 2023 to develop new rare disease therapies

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by Steve Bryson, PhD |

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The U.S. Food and Drug Administration (FDA) has selected nomlabofusp, an investigational treatment for Friedreich’s ataxia (FA), to participate in the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program.

Launched by the FDA in September 2023, the milestone-driven program seeks to accelerate the development of new therapies that address an unmet medical need for rare diseases through enhanced communication with the agency.

“We are thrilled nomlabofusp … has been selected by the FDA to participate in the START pilot program,” Carole Ben-Maimon, MD, president and CEO of Larimar Therapeutics, the therapy’s developer, said in a company press release. “This selection highlights the commitment of the FDA to augment currently available formal meeting communications with more rapid, ad hoc communication mechanisms with the goal of accelerating the pace of development of nomlabofusp.”

In FA, a deficiency in the frataxin protein impairs the function of energy-producing mitochondria, which affects cells with high-energy demands, such as nerves and muscles. This leads to a loss of muscle control and coordination, or, ataxia, along with heart and neurological problems.

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Why was nomlabofusp chosen for START?

Nomlabofusp is a lab-made version of frataxin modified to access mitochondria, with the goal being to restore energy production and ease FA symptoms.

Previously called CTI-1601, it’s one of six new drugs selected for START, three by the Center for Drug Evaluation and Research (CDER) and three by the Center for Biologics Evaluation and Research (CBER).

START selection was based on the readiness of a therapy’s developmental program. Along with addressing unmet medical needs in a rare neurodegenerative condition, nomlabofusp’s clinical development plans align with chemistry, manufacturing, and controls (CMC) development timelines. CMC refers to procedures that assess the physical and chemical characteristics of a drug and ensure quality and consistency during manufacturing.

Eligibility is also based on a proposed communications plan, whereby enhanced communication with the FDA could accelerate the launch of a pivotal study and the submission of a request for approval in the form of a Biologics License Application (BLA).

“Participating in the START program enables increased communication with the FDA to help expedite the progression of our nomlabofusp development program to the pre-BLA meeting stage,” said Russell Clayton, Larimar’s chief medical officer. “This is important to patients who are continuing to live with this devastating disease.”

In a Phase 2 dose exploration trial (NCT05579691) with 28 adults with FA, nomlabofusp, given as an injection under the skin, increased frataxin levels in skin cells in a dose-dependent manner. Before treatment, levels were below those of healthy adults, but rose to higher than normal levels after two weeks.

In 2021, the FDA placed a clinical hold on nomlabofusp’s development program, citing safety concerns with nonhuman primates. The hold was partially lifted in 2022, which allowed clinical testing at 25 mg and then at 50 mg last year. The agency removed the partial hold in May after reviewing the Phase 2 data.

Nomlabofusp is being tested in an open-label extension (OLE) study to assess its long-term safety, tolerability, and pharmacological properties, along with frataxin levels in tissues from FA patients. The OLE includes patients who participated in previous nomlabofusp clinical trials.

Participants will receive 25 mg daily doses, administered by patients or their caregivers, with plans to escalate to 50 mg. The data will be compared with those from an external control group from the FA Clinical Outcome Measures Study (NCT03090789). Sponsored by the Friedreich’s Ataxia Research Alliance (FARA), the study follows the natural history of FA.

“We look forward to participating in this pilot program and working with the FDA to further the development of nomlabofusp, which has the potential to address the root cause of Friedreich’s ataxia by increasing frataxin levels,” Ben-Maimon said.