The European Commission has granted NLX-112 (Neurolixis), a highly selective serotonin 5-HT1A receptor agonist, orphan medicinal product designation for the treatment of spinocerebellar ataxia (SCA), following a positive recommendation from the Committee for Orphan Medicinal Products. This decision underscores the potential of NLX-112 to address the unmet needs of patients suffering from this rare and debilitating genetic disorder.
The designation was supported by collaborative research between Neurolixis and Patricia Maciel’s team at the University of Minho in Portugal, funded by the United States Department of Defense. Their preclinical work demonstrated that NLX-112 significantly reduced motor dysfunction in models of SCA type 3 (SCA3), also known as Machado-Joseph Disease.
Preclinical Evidence and Mechanism of Action
"Serotonin plays a crucial role in motor control, and our research shows that NLX-112 can mitigate the motor impairments seen in transgenic models of SCA3. This finding suggests that NLX-112 has the potential to improve the lives of patients suffering from this devastating disorder," said Patricia Maciel, PhD, an associate professor at the University of Minho School of Medicine.
NLX-112, also known as befiradol, is an oral drug that selectively activates serotonin 5-HT1A receptors. This mechanism of action has shown efficacy in preclinical models of motor disorders. Clinical testing has included over 600 patients with various nonmotor indications, supporting its potential in neurological treatments. In a phase 2a trial (NCT05148884) for Parkinson's disease (PD), NLX-112 demonstrated positive results in patients with levodopa-induced dyskinesia (LID).
Benefits of Orphan Drug Designation
The orphan medicinal product designation provides significant benefits for NLX-112, including 10 years of market exclusivity in the European Union after marketing approval. Neurolixis may also be granted an additional 2 years of exclusivity upon successful compliance with a pediatric assessment plan.
"This designation is a critical milestone for Neurolixis as we expand our drug development programs targeting rare neurological disorders. With NLX-112, we are making strides in the field of movement disorders, including Spinocerebellar Ataxia, and this designation further solidifies our commitment to advancing treatments for rare diseases," stated Adrian Newman-Tancredi, PhD, DSc, chief executive officer at Neurolixis.
Spinocerebellar Ataxia: An Unmet Need
SCA comprises a group of rare, genetic disorders causing progressive neurological symptoms such as clumsiness, muscle weakness, and tremors. SCA3, the most common form, leads to difficulties in speech and swallowing, a staggering gait, and sometimes dystonia or Parkinson's-like symptoms. Currently, there is no cure or approved treatment for SCA3, which typically begins in adolescence and can lead to paralysis.
Prior Clinical Findings
NLX-112's efficacy was highlighted at the 2023 International Congress of Parkinson’s Disease and Movement Disorders, where it met the primary endpoint of safety and tolerability and the secondary endpoint of significantly reducing LID. The randomized, double-blind, placebo-controlled trial, conducted across five centers in Sweden, involved 22 patients (NLX-112, n = 15; placebo, n = 7) who completed the 8-week treatment. Safety results were positive, with no significant differences between the NLX-112 and placebo groups, and no serious adverse events were reported in the NLX-112 group.
Neurolixis' Broader Pipeline
In addition to NLX-112, Neurolixis is advancing NLX-101 in a phase 1 study for rare autism spectrum disorders, such as Fragile X and Rett syndromes. The company is also developing NLX-204, a preclinical candidate showing promise as a rapid-acting antidepressant and analgesic using a non-opioid mechanism.
