Rare Daily Staff
Larimar Therapeutics said its previously announced private placement of $95 million has been terminated after the U.S. Food and Drug Administration placed a clinical hold on its experimental Friedreich’s ataxia therapy CTI-1601.
The clinical hold followed notification by the company to the FDA of the death of non-human primates treated with the highest dose levels of CTI-1601 in an ongoing 180-day toxicology study. In the clinical hold letter, the FDA stated it needs a full study report from the ongoing non-human primate study and Larimar may not initiate additional clinical trials until the company has submitted the report and received notification from the agency that additional clinical trials may commence.
Friedreich’s ataxia (FA) a is progressive, neurodegenerative condition caused by mutations in the FXN gene. Signs and symptoms usually begin in puberty and lead to progressive impaired muscle coordination, gradual loss of muscle strength and sensation in the arms and legs, muscle stiffness, and impaired speech.
CTI-1601 is a recombinant fusion protein intended to deliver human frataxin into the mitochondria of patients with Friedreich’s ataxia who are unable to produce enough of this essential protein. Currently in phase 1 clinical trials in the U.S., CTI-1601 has been granted Rare Pediatric Disease designation, Fast Track designation and Orphan Drug designation by the U.S. Food and Drug Administration (FDA), Orphan Drug Designation by the European Commission, and PRIME designation by the European Medicines Agency.
“While the notification of a formal clinical hold is disappointing, it does not change our previously stated clinical development strategy for CTI-1601,” said Carole Ben-Maimon, president and CEO of Larimar. “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.”
She said based on all of the information the company has regarding CTI-1601’s safety profile to date, the company believes there is a path forward toward the initiation of its Jive and pediatric MAD trials. However, due to the additional regulatory requirements that come with responding to a formal clinical hold, the initiation of these trials may be delayed into 2022.
As of March 31, 2021, Lorimar had $81.4 million in cash and investments, which provides cash runway through the first half of 2022.
The company said the safety of CTI-1601 was previously evaluated in phase 1 single- and multiple-ascending dose clinical trials. Recently announced data from these trials indicate that repeated subcutaneous injections of CTI-1601 were generally well tolerated at doses up to 100 mg administered daily for 13 days. No serious adverse events, important medical events, or treatment-related severe adverse events were reported in the trial and the number and severity of adverse events did not increase with increasing exposure to CTI-1601.
The most common adverse events were mild and moderate injection site reactions. Data from the MAD trial also showed that daily subcutaneous injections of CTI-1601 at doses of 50 mg or 100 mg resulted in frataxin levels in peripheral tissues (buccal cells) that were at, or in excess of, those that would be expected in phenotypically normal heterozygous carriers.
Photo: Carole Ben-Maimon, president and CEO of Larimar Therapeutics