Use of newly named drug leads to stable motor symptoms in Parkinson’s

Gain Therapeutics’ oral therapy candidate rexaceract, formerly called GT-02287, stabilized motor symptoms in a small group of people with Parkinson’s disease who were treated for one year.

That’s according to new data from an open-label extension of an early clinical trial, which showed no meaningful progression of Parkinson’s motor symptoms for any of the evaluable participants taking rexaceract. The study involved people with and without genetic factors that may increase the risk of Parkinson’s.

The findings, “Long-Term Open-Label Data on the GCase Modulator GT-02287 (Rexaceract) in People with Parkinson’s Disease,” were presented by Joanne Taylor, PhD, Gain’s chief scientific officer, at the International Congress of Parkinson’s Disease and Movement Disorders, now being held in Seoul, South Korea. Gain stated in a company press release that these data, stemming from a Phase 1b trial, offer preliminary clinical evidence supporting the drug’s potential as a disease-modifying treatment for Parkinson’s.

“We believe rexaceract has the potential to shift the treatment paradigm beyond symptom management by addressing the underlying biology of Parkinson’s disease, and we expect rexaceract to be the backbone of the next generation of treatment for Parkinson’s,” said Gene Mack, Gain’s president and CEO.

The company said it now plans to submit a new Phase 2 trial protocol to the U.S. Food and Drug Administration in the coming weeks, incorporating information from this study. That new mid-stage trial is expected to start the trial at the beginning of 2027, per the developer.

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A progressive disease, Parkinson’s is marked by the buildup of toxic clumps of alpha-synuclein protein, which is thought to contribute to the loss of nerve cells that produce dopamine, a signaling molecule involved in motor function. Genetic factors, such as mutations in the GBA1 gene, may increase a person’s risk of developing Parkinson’s.

The GBA1 gene provides instructions to produce glucocerebrosidase, known as GCase, an enzyme that breaks down and recycles certain fatty molecules, such as glucosylsphingosine (GluSph), inside lysosomes, the cell’s recycling centers. GBA1 mutations reduce GCase activity, which can contribute to lysosomal dysfunction and to alpha-synuclein accumulation.

Rexaceract showed lasting benefits, backing its development

Rexaceract is a small molecule designed to bind GCase and restore its function. This is expected to prevent alpha-synuclein from clumping in the brain, thereby slowing Parkinson’s progression. The treatment is being developed for people with Parkinson’s regardless of GBA1 mutations, as GCase function may also be impaired in individuals without these mutations.

Preclinical studies in animal models of Parkinson’s demonstrated that rexaceract restored GCase activity and reduced alpha-synuclein accumulation, nerve cell damage, and loss. The treatment also improved motor function and preserved more complex behaviors in mice, suggesting it may slow disease progression.

In a subsequent Phase 1 trial involving healthy volunteers, rexaceract was shown to be generally safe and well tolerated. The experimental treatment also reached the cerebrospinal fluid (CSF), the liquid that surrounds the brain and spinal cord, and increased GCase activity at clinically relevant doses.

Now, a Phase 1b clinical trial (NCT06732180) tested rexaceract, given once daily for 90 days, at a dose of 13.5 mg/kg/day. The study enrolled 21 people with Parkinson’s with or without GBA1 mutations, ages 30 to 85, diagnosed within the previous seven years.

Initial results showed that, over about three months of treatment, rexaceract was safe and led to a reduction in the CSF levels of GluSph, a substrate of GCase. Among nine patients with available data, the treatment also eased motor symptoms and helped patients maintain daily activities.

For the new analysis, 16 participants entered the trial’s nine-month extension, with 13 completing one year of treatment. Among 12 evaluable participants, there was no meaningful progression of motor symptoms, the new data show. The researchers noted specifically that scores on the MDS-sponsored Revision of the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II and III — which assess motor aspects, activities of daily living, and motor symptoms — remained stable.

The stabilization of motor symptoms was similar among participants with high and low GluSph levels before treatment, the data showed.

The stabilization of MDS-UPDRS scores [which would signify worsening symptoms] over one year of treatment with rexaceract … is particularly encouraging.

“Seeing MDS-UPDRS scores remain stable after a full year of dosing is an important clinical milestone for rexaceract,” Mack said, adding that these data “[give] us greater confidence in the durability of the clinical profile we are seeing and [strengthen] our conviction as we advance rexaceract into the next stage of development.”

No new safety signals emerged during the trial’s extension, and most treatment-emergent adverse events were mild, the researchers noted. Further, per the team, transient increases in liver enzymes seen during the initial treatment period, which can indicate liver damage, did not occur during the extension.

According to Taylor, “the stabilization of MDS-UPDRS scores over one year of treatment with rexaceract regardless of biomarker stratification is particularly encouraging.”