EMA recommends NUZ-001 for orphan drug status in Europe
Phase 1 trial data show treatment may slow ALS progression
The European Medicines Agency (EMA) has recommended that monepantel, now named NUZ-001, be granted orphan medicinal product designation to treat amyotrophic lateral sclerosis (ALS).
The positive opinion will be reviewed by the European Commission, which is expected to issue a final decision in December. If granted, the designation will provide developer Neurizon Therapeutics with incentives including reduced regulatory fees, assistance with trial protocols, and 10 years of market exclusivity if an approval is ultimately granted.
NUZ-001 received a similar designation in the U.S. earlier this year.
A veterinary drug, monepantel was being repurposed by PharmAust to treat ALS. The company recently changed its name to Neurizon, which prompted monepantel’s name change to NUZ-001.
‘Critical milestone’ for company
“Receiving a positive opinion from the EMA for Orphan Medicinal Product Designation is a critical milestone for Neurizon,” Michael Thurn, PhD, Neurizon’s managing director and CEO, said in a company press release. With the designation, “along with the Orphan Drug Designation from the United States Food and Drug Administration, we have secured market exclusivity for NUZ-001 across the world’s key markets for the treatment of ALS,” he said.
NUZ-001 is a deworming agent widely used in veterinary medicine. But it also seems to work as a potent inhibitor of the mTOR signaling pathway, which is important for cell growth and survival and for clearing out defective components or molecules from cells.
By activating this pathway, the medication may help to protect nerve cells and clear the misfolded proteins that accumulate to toxic levels in virtually all ALS patients.
Data from a Phase 1 trial called MEND (NCT04894240) has generally supported this hypothesis.
In the trial, 12 ALS adults received a high or a low dose of NUZ-001, given daily in the form of oral tablets. Compared with before treatment, patients showed no significant changes in disease severity as measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), indicating a slowing of disease progression in these patients.
When the two groups were compared with matched controls from previous ALS clinical studies, disease progression was 39% slower with the low NUZ-001 dose and 58% slower with the high dose. While no survival data was yet available, a computer model estimated that these benefits could translated into a meaningful survival benefit of up to 4.5 years.
After completing MEND, all patients continued to receive NUZ-001 via a compassionate use program, which allows patients to receive experimental therapies. Ten participants then joined an open-label extension to receive the treatment at the high dose for one year.
Data after four months in the extension study showed that patients on NUZ-001 continued to have a slower rate of ALSFRS-R progression, by 43.2%, compared with the historical, matched controls. During that period, more than half of patients on the experimental therapy (56%) experienced no worsening in their ALSFRS-R scores.
NUZ-001 also helped patients live significantly longer, resulting in an 80.3% lower risk of death compared with the untreated patients from the historical database.
Based on the promising findings, NUZ-001 has been selected for Phase 2/3 testing within the HEALEY ALS Platform Trial, which is investigating multiple ALS candidate treatments at the same time to shorten development timelines.
Enrollment is expected to start early next year. If positive, results could lead to NUZ-001 accelerated approval, according to the company.
“This important recognition highlights the significant potential of NUZ-001 to provide a meaningful therapeutic option for patients with ALS,” Thurn said. “We look forward to further engagement with the EMA and other regulators as we advance our mission to deliver innovative treatments to patients battling this devastating disease.”
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