The European Medicines Agency (EMA) has issued a positive opinion recommending orphan medicinal product designation for monepantel, now known as NUZ-001, for the treatment of amyotrophic lateral sclerosis (ALS). This decision, which is pending final approval from the European Commission in December, offers Neurizon Therapeutics potential benefits including reduced regulatory fees, trial protocol assistance, and 10 years of market exclusivity upon approval. NUZ-001 had previously received orphan drug designation in the U.S. earlier this year.
Mechanism of Action and Clinical Data
NUZ-001, originally a veterinary deworming agent, is being repurposed for its potential to inhibit the mTOR signaling pathway. This pathway is crucial for cell growth, survival, and the clearance of defective cellular components. By activating mTOR, NUZ-001 may protect nerve cells and facilitate the removal of toxic misfolded proteins, a hallmark of ALS.
Phase 1 trial data from the MEND study (NCT04894240) provides preliminary support for this mechanism. The trial involved 12 ALS patients who received either a high or low daily oral dose of NUZ-001. Results indicated that patients experienced no significant changes in disease severity as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), suggesting a slowing of disease progression. When compared to matched controls from prior ALS clinical studies, disease progression was reportedly 39% slower in the low-dose group and 58% slower in the high-dose group. While survival data was not yet available, modeling suggested a potential survival benefit of up to 4.5 years.
Continued Treatment and Extended Study Results
Following the MEND trial, all participants continued NUZ-001 treatment through a compassionate use program. Ten of these patients then enrolled in an open-label extension study, receiving the high dose for one year. Data from the first four months of the extension study indicated a 43.2% slower rate of ALSFRS-R progression compared to historical controls. Notably, over half (56%) of the patients on NUZ-001 experienced no worsening of their ALSFRS-R scores during this period. Furthermore, NUZ-001 was associated with an 80.3% reduction in the risk of death compared to untreated patients from a historical database.
Path to Phase 2/3 Trial
Based on these promising findings, NUZ-001 has been selected for Phase 2/3 testing within the HEALEY ALS Platform Trial. This platform trial design allows for the simultaneous investigation of multiple ALS candidate treatments, potentially accelerating development timelines. Enrollment is anticipated to commence early next year, and positive results could pave the way for accelerated approval of NUZ-001.
Company Perspective
"Receiving a positive opinion from the EMA for Orphan Medicinal Product Designation is a critical milestone for Neurizon," said Michael Thurn, PhD, Neurizon’s managing director and CEO. He added that the designation, combined with the Orphan Drug Designation from the FDA, secures market exclusivity for NUZ-001 in key global markets for ALS treatment. "This important recognition highlights the significant potential of NUZ-001 to provide a meaningful therapeutic option for patients with ALS," Thurn concluded.
