Low-dose CTI-1601 safely increases frataxin in skin, mouth cells

FA patients see benefits of Larimar therapy after 14 days in trial

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Two hands, a stethoscope, and a handful of pills surround a graph labeled clinical trials and showing data.

CTI-1601, an experimental therapy by Larimar Therapeutics, is generally well tolerated by people with Friedreich’s ataxia (FA) and increases the levels of frataxin, a protein they’re missing, in their skin and mouth (buccal) cells after two weeks.

That’s according to top-line data from the first group of patients in a Phase 2 trial (NCT05579691) testing the treatment’s safety. The participants received either 25 mg of CTI-1601 or a placebo as an under-the-skin (subcutaneous) injection, given once a day for 14 days and then every other day for 14 days more

“Our preliminary Phase 2 data provide the first clinical indication that a 25 mg dose of CTI-1601 can increase frataxin levels in peripheral tissues, building upon our proof-of-concept Phase 1 results,” Carole Ben-Maimon, MD, Larimar’s president and CEO, said in a press release.

“Importantly, the frataxin increases achieved with a relatively low 25 mg dose in our Phase 2 trial suggest a continuous daily dosing regimen is preferred for maintaining increases achieved with 25 mg CTI-1601,” Ben-Maimon added.

Larimar submitted these data for review by the U.S. Food and Drug Administration (FDA) and will meet with the agency later this quarter to discuss other requirements needed for FDA clearance to test a higher dose of CTI-1601. The FDA still maintains a partial clinical hold on the CTI-1601 program, which had been paused in 2021 due to safety concerns and a request for more data.

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FDA Keeps Hold on CTI-1601 Clinical Testing, Awaits More Data

Data suggest frataxin levels reach a steady state after 14 days

The company said in the release that it expects to provide updates in the third quarter of this year on “the next steps for the CTI-1601 program” — after Larimar has gotten “feedback” from the FDA.

The first goal is to move forward with testing a higher dose of 50 mg in people with FA.

“Our Phase 2 results add to our safety database indicating that CTI-1601 is generally well tolerated,” Ben-Maimon said. “We believe the safety, pharmacokinetic, and pharmacodynamic data generated to date support evaluation of a 50 mg dose of CTI-1601 in our Phase 2 trial.”

In FA, individuals produce too little frataxin, a protein required for the normal functioning of mitochondria, the energy-producing units of cells. This can cause many symptoms, from muscle weakness and trouble with balance and coordination to vision and hearing loss. 

CTI-1601 is an engineered fusion protein designed to deliver the missing frataxin to mitochondria. In so doing, it’s expected to restore the normal functioning of mitochondria, which may help ease the symptoms of FA.

An earlier Phase 1 trial (NCT04519567) showed that CTI-1601, given daily for up to 13 days, brought about a dose-dependent increase in frataxin levels in the skin, buccal cells, and and platelets, which are tiny blood cells involved in blood clotting. The treatment was well tolerated, with no serious side effects in people with FA.

The goal of the Phase 2 trial is to test how safe and well tolerated CTI-1601 is versus a placebo in people ages 18 and older. It’s also testing CTI-1601’s pharmacokinetics, or its movement into, through, and out of the body, and its pharmacodynamics, which is its effects in the body.

The first group to take part in the trial comprised 13 patients with a genetically confirmed diagnosis of FA. Nine patients, with a mean age of 37.8, were randomly assigned to receive 25 mg of CTI-1601. The remaining four patients, who had a mean age of 34, received a placebo.

Among the patients receiving CTI-1601, all but one completed the trial. That patient left the trial due to an allergic reaction to CTI-1601, which resolved with standard treatment, the company shared in the presentation to a webcast that went live May 15.

After the first 14 days, frataxin levels increased in the skin and buccal cells of the patients who received CTI-1601, but not in those who received a placebo.

Our Phase 2 results add to our safety database indicating that CTI-1601 is generally well tolerated. … We believe the safety, pharmacokinetic, and pharmacodynamic data generated to date support evaluation of a 50 mg dose of CTI-1601 in our Phase 2 trial.

Taking into account the change in skin frataxin levels in the placebo group, the median increase in the CTI-1601 group from the trial’s start (baseline) was of 3.47 picograms per microgram of total protein levels. In buccal cells, the median increase was of 0.91.

Pharmacokinetic data suggested that frataxin levels reached a steady state after 14 days. Safety data indicated that CTI-1601 was generally well tolerated, with no serious side effects reported. 

The most common side effects were mild or moderate reactions at the site of injection.

“I would like to thank all those who participated in our trials and look forward to our upcoming meeting with the FDA later this quarter,” Ben-Maimon said.