First FA patient dosed in OLE study of nomlabofusp, formerly CTI-1601

Study is first testing daily 25 mg subcutaneous injection

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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The first patient has been dosed in a long-term, open-label extension (OLE) of a Phase 2 dose escalation study that tested nomlabofusp, formerly CTI-1601, an investigational therapy being developed by Larimar Therapeutics for Friedreich’s ataxia (FA).

The OLE study is open to patients who took part in the completed Phase 2 study (NCT05579691) or an earlier Phase 1 study (NCT04176991 or NCT04519567). It’s initially testing daily 25 mg injections administered under the skin, or subcutaneously, by patients or their caregivers.

“We are pleased to dose the first patient in our OLE study, further advancing the nomlabofusp clinical program and building on the successful completion of our Phase 2 dose escalation study,” Carole Ben-Maimon, MD, Larimar’s president and CEO, said in a press release.

The company plans to include initial data from the OLE study, expected late this year, along with data from the completed studies as part of a biologics license application (BLA) package toward nomlabofusp’s accelerated approval in the U.S. This “information will be used to help support a potential BLA submission for accelerated approval targeted for the second half of 2025,” Ben-Maimon said.

FA is a neurodegenerative disease caused by mutations in the FXN gene, which provides instructions for making the protein frataxin, which is needed for the healthy functioning of mitochondria, the bean-shaped structures that produce energy for cells. When frataxin is lacking, energy output is reduced. Without enough energy, nerve and muscle cells, which have high energy needs, become damaged, leading to a range of symptoms.

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What is nomlabofusp?

Nomlabofusp uses a recombinant, or lab-made, protein to deliver a version of frataxin to mitochondria. Once the carrier is cleaved off, the frataxin becomes fully functional and helps restore energy output from mitochondria, which should ease symptoms.

The OLE study will test how safe nomlabofusp is, its pharmacokinetics, or how it moves into, through and out of the body, and its effects on frataxin levels in the body. Other markers, such as the levels of fats and the activity of certain genes, are also being measured.

“The OLE study will inform on the long-term safety profile and tissue frataxin levels and provide a first look at real-life experience with self-administration by patients or administration by a caregiver,” Ben-Maimon said. 

Clinical data from the OLE study will be compared with data from an external control group registered with the FA Clinical Outcome Measures Study (NCT03090789), a natural history study sponsored by the Friedreich’s Ataxia Research Alliance (FARA).

To be allowed to escalate the dose in the OLE study, data from those treated with 50 mg of nomlabofusp in the Phase 2 study, along with data from the 25 mg dose, will be filed with the U.S. Food and Drug Administration (FDA) for review.

The FDA placed the clinical program on hold in 2021 due to safety concerns. The hold was partially lifted in 2022 to allow clinical testing of the 25 mg dose. Larimar was cleared last year to test the 50 mg dose in up to 15 patients given either nomlabofusp or a placebo.

Top-line data from the Phase 2 study showed that daily subcutaneous injections of nomlabofusp resulted in dose-dependent increases in the levels of frataxin and that it was well tolerated at both doses, with no serious side effects reported.

Based on these data, “in February we announced that we intend to pursue frataxin as a potential novel surrogate endpoint to support accelerated approval,” pending the outcome of ongoing discussions with the FDA, Ben-Maimon said. A surrogate endpoint doesn’t measure the clinical benefit of primary interest in and of itself, but rather is a substitute measure that’s expected to predict that clinical benefit. If it’s accepted by the FDA, the surrogate endpoint may help support nomlabofusp’s accelerated approval.