Nomlabofusp leads to long-term frataxin gains for FA patients: Data
Developer expects to seek FDA accelerated approval for injection therapy
Daily use of the experimental therapy nomlabofusp is leading to long-term clinical improvements and increases in frataxin levels for people with Friedreich’s ataxia (FA) relative to what would be expected in the absence of treatment.
That’s according to new data from an ongoing open-label extension study (NCT06447025) that’s testing nomlabofusp’s long-term safety and effectiveness in adults and adolescents with FA. The study is enrolling by invitation in the U.S.
A few serious allergic reactions have occurred, prompting treatment developer Larimar Therapeutics to adjust the dosing regimen going forward. The company also plans to expand the study to children ages 2-11 in the future.
“The long-term clinical data [now being] presented … reinforce our conviction in the potential of nomlabofusp to address the root cause of FA and be the first potential disease modifying therapy,” Carole Ben-Maimon, MD, president and CEO of Larimar, said in a company press release. Ben-Maimon noted the “consistent directional improvements across [four] key clinical outcomes observed in the [open-label] study.”
Larimar has shared all clinical updates with the U.S. Food and Drug Administration (FDA) — the company has been in regular communication with the agency through its participation in the START pilot, fully called the Support for Clinical Trials Advancing Rare Disease Therapeutics program.
Larimar expects to submit an application to the FDA next year seeking nomlabofusp’s accelerated approval for FA. Regulators have already provided guidance on the application’s requirements.
Plans for global Phase 3 trial now in the works, per Larimar
The company also plans to launch a global Phase 3 clinical trial, with identified sites in the U.S., Canada, Australia, the U.K., and the European Union now going through the qualification process.
Jennifer Farmer, CEO of the Friedreich’s Ataxia Research Alliance (FARA), noted that “FA is a relentlessly progressive disease that is life-altering and can be life-shortening.”
Farmer said FARA is “encouraged by” the positive outcomes seen thus far in the extension study.
“Treatment approaches, like nomlabofusp, that target the root cause of FA … are of great interest to the FA community,” Farmer said.
People with FA are deficient in frataxin, an important protein for the proper function of mitochondria, which are the organelles that produce most cellular energy. The disease’s hallmark symptom is ataxia, a loss of muscle control and coordination.
Formerly known as CTI-1601, nomlabofusp is designed to deliver a lab-made version of frataxin that’s been modified to better enter cells and reach the mitochondria. When given via daily under-the-skin, or subcutaneous, injections, the treatment is expected to restore more normal energy production and to ease FA symptoms.
FA is a relentlessly progressive disease. … Treatment approaches, like nomlabofusp, that target the root cause of FA … are of great interest to the FA community.
The OLE, which started dosing last year, is evaluating the long-term effects of nomlabofusp in FA patients. It initially enrolled adults who had completed treatment in previous Phase 1 or Phase 2 nomlabofusp clinical trials, but has since been expanded to involve adolescents, ages 12-17, from a separate run-in study (NCT06681766), as well as participants who had not previously received nomlabofusp.
In the study, all participants receive daily subcutaneous injections of the treatment, either self-administered or given by a caregiver. The daily dose was 25 mg at the start, which was later increased to 50 mg. As of Aug. 27, 39 OLE participants had received at least one dose of nomlabofusp, according to its developer.
Patients given nomlabofusb in study saw greater skin frataxin levels
These newly reported results show that nomlabofusp led to increased skin frataxin levels among participants. All 10 individuals with at least six months of data achieved frataxin levels more than 50% of what’s typically seen in healthy people, the data showed.
“Importantly, achieving tissue [frataxin] levels equivalent to more than 50% of those found in healthy volunteers means participants are at levels found in asymptomatic carriers who do not develop the disease,” Ben-Maimon said.
The frataxin increases were associated with consistent trends toward improvement in key clinical outcomes after a year of treatment. This included a median 2.25-point reduction in scores on the modified Friedreich Ataxia Rating Scale (mFARS), a standard measure of disease progression.
In contrast, data from an external matched group of untreated FA patients showed that mFARS scores increased, or worsened, by a median of 1 point.
Other clinical measures of physical function and fatigue also tended to improve with nomlabofusp relative to the natural history group, according to the researchers.
Among those who received long-term daily dosing — 14 people on the therapy for at least six months and eight on it for more than a year — nomlabofusp was generally well tolerated. The most common side effects were mild or moderate injection site reactions.
Nomlabofusb dose lowered after life-threatening allergic reactions
Seven people experienced anaphylaxis, a life-threatening allergic reaction, and withdrew from the study. These events usually occurred on the first day of treatment and always happened within the first six weeks, per the developer.
Larimar consulted experts and decided to modify the dosing regimen to address this complication. The FDA agreed with this change. The new regimen will involve a test dose under careful observation and a slower increase to the full 50 mg dose.
FARA’s Farmer noted that FA patients and their families are “informed and engaged,” understanding that “therapies come with side effects and risks that must be evaluated in the context of potential benefit.”
The planned Phase 3 trial is expected to enroll approximately 100-150 FA patients, ages 2-40, who can still walk. Participants will be randomly assigned to receive daily nomlabofusp (50 mg) or a placebo for about 1.5 years. The main goals will be to evaluate safety, mFARS scores, and upright stability.
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