Nomlabofusp dosing started for adolescents in Phase 1 study
Dosing patients 12-17 is 'first step' in testing therapy's safety in children
Adolescents with Friedreich’s ataxia (FA) are now being dosed with nomlabofusp as part of a placebo-controlled Phase 1 clinical study that’s testing Larimar Therapeutics‘ subcutaneous, or under-the-skin, injection therapy.
Data from the Phase 1 study, and from other clinical testing of nomlabofusp, are expected by the middle of this year, Larimar said in a company press release.
The study is still recruiting patients ages 12 to 17 at a single site in Maryland. The company also plans to begin enrolling younger patients — children ages 2 to 11 — in the first half of this year. Each group, or cohort, will comprise 12 to 15 patients, who will be randomly assigned to receive a weight-based dose of nomlabofusp or a placebo, for one week.
“Dosing adolescents is the first step in evaluating the safety and [pharmacological properties] of nomlabofusp in pediatric patients with FA,” said Rusty Clayton, a board-certified pediatric pulmonologist and Larimar’s chief medical officer. Clayton noted that the study is assessing nomlabofusp’s pharmacokinetics, or the movement of the drug into, through, and out of the body.
Phase 1 study plans to also enroll younger children in coming months
To be eligible for this run-in study (NCT06681766), patients must be able to move 25 feet, with or without an assistive device, and to sit upright, as well as transfer from their bed to a chair safely, and eat and take care of their personal hygiene with little help. A run-in study is designed to enroll participants and assess their adherence, among other factors, before fully committing them to clinical testing.
Those adolescents receiving the therapy will be given a weight-based dose that’s equivalent to the 50 mg adult dose, according to the company. Treatment will be administered daily for seven days.
Participants who complete the study will be screened to join an ongoing open-label extension (NCT06447025), known as an OLE for short, in which they would receive nomlafobusp daily for as long as two years.
“We expect to transition both the adolescents and children into the ongoing OLE study after assessing safety and exposure data from each successive cohort,” Clayton said.
Data from both the adults now in the OLE and the adolescents in the Phase 1 study are expected this summer, according to Clayton.
“We look forward to reporting long-term 50 mg data in adults from our OLE study, as well as available data from adolescents completing the pediatric [pharmacokinetics] run-in study, in mid-2025,” Clayton said.
FA is caused by mutations in the FXN gene, which provides instructions for producing a protein called frataxin. This protein is needed for the healthy functioning of mitochondria, the bean-shaped structures that output the energy cells use to run their activities.
Nomlabofusp, formerly known as CTI-1601, makes use of a recombinant, or lab-made, carrier to deliver a version of frataxin to mitochondria. Once the carrier is cleaved off, frataxin becomes fully functional and helps to restore the energy produced by mitochondria. This is expected to ease FA symptoms caused by a missing or faulty frataxin.
We expect to transition both the adolescents and children into the ongoing OLE [open-label extension] study after assessing safety and exposure data from each successive cohort [patient group]. … We look forward to reporting long-term 50 mg data in adults … as well as available data from adolescents completing the pediatric … study, in mid-2025.”
An early Phase 2 dose-exploration study (NCT05579691), completed in late 2023, tested two nomlabofusp doses — 25 and 50 mg — against a placebo in 28 adults with FA. The results showed dose-dependent increases in frataxin levels in cells of the skin and inside the mouth after daily treatment for two weeks, followed by every other day use for two additional weeks. Nomlabofusp was well tolerated at both doses, with no serious side effects.
The OLE, which is open to all patients who’ve participated in earlier clinical studies of nomlabofusp, is testing how safe and well tolerated nomlabofusp is when given long-term as a subcutaneous injection. It’s also measuring the levels of frataxin in cells of the mouth and the skin, and watching for changes in the levels of blood fats and other clinical measures.
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