FDA Places Hold on Friedreich’s Ataxia Candidate After Nonhuman Primate Deaths


The U.S. Food and Drug Administration (FDA) placed a clinical hold on Larimar Therapeutics lead Friedreich’s ataxia (FA) asset, CTI-1601 after the company reported deaths in the highest dose levels of a nonhuman primate toxicology study.

CTI-1601 is Larimar’s recombinant fusion protein designed for human frataxin delivery into the mitochondria of patients with FA who are incapable of producing sufficient quantities of the protein. The asset is currently undergoing investigation in Phase I clinical trials in the U.S. 

Topline phase I trial findings announced earlier this month showed that daily subcutaneous injections of the agent for nearly two weeks were associated with dose-dependent increases in frataxin levels compared with placebo. Doses of CTI-1601 were generally well tolerated at up to 100 mg per day for 13 days. 

“The ability of CTI-1601 to elevate frataxin in the evaluated tissues strongly supports its continued clinical evaluation, as frataxin levels in buccal cells and blood have been shown to be associated with disease severity in FA patients,” according to a statement made by Larimar’s President and Chief Executive Officer, Carole Ben-Maimon, MD.


Dr. Ben-Maimon added that the Phase I results “are exciting and represent a critical step forward in CTI-1601’s development as a frataxin replacement therapy for patients with FA,” considering CTI-1601 is the only therapeutic candidate “in clinical development that is designed to supplement frataxin levels in patients with FA, thus addressing the root cause of the disease.”

The FDA had previously granted the agent Rare Pediatric Disease designation, Fast Track designation, and Orphan Drug designation. Additionally, the European Medicines Agency has given CTI-1601 Priority Medicines (PRIME) designation, while the European Commission has granted the candidate Orphan Drug Designation.

In the ongoing, 180-day non-human primate toxicology study, Larimar reported several deaths at the highest dose levels of the candidate. This set off warning bells for the FDA, which stated it would need a full study report from the study before Larimar can continue the study or initiate other clinical trials.

“While the notification of a formal clinical hold is disappointing, it does not change our previously stated clinical development strategy for CTI-1601,” Dr. Ben-Maimon said in a statement. “Patient safety is our top priority, and we will continue with our plan to complete the NHP toxicology study, assess the data, and discuss that data with FDA to obtain their consent prior to initiating our Jive and pediatric MAD trials.” 

Dr. Ben-Maimon noted that the company stands firm in its belief that CTI-1601 has “a path forward” in additional trials, given the accumulated knowledge regarding the agent’s safety profile. But with the clinical hold in place, the company expects the initiation of the Jive and pediatric MAD trials might be delayed until next year. 

Late last week, Larimar released a statement that it was looking to raise $95 million in a private placement, financing which would have been funneled toward the drug’s development. Financing would have been garnered on the issuance of approximately 7,096,048 shares of common stock at a share price of $13.43. However, the clinical hold places a damper on the company’s plans to close the private financing.

Larimar says that despite its termination of the private placement financing, the company still has up to “$81.4 million in cash and investments,” funding which supports “cash runway through the first half of 2022.” 


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