Miglustat Shows Promise in Stabilizing Vision in Juvenile Batten Disease
核心洞察
Treatment with Batten-1 (miglustat) for 18 months showed no signs of deteriorating vision in patients with juvenile Batten disease (搜索).
The Phase 1/2 study demonstrated that Batten-1 was safe and well-tolerated over two years, with potential stabilization of visual acuity.
A Phase 3 trial, with visual acuity as the primary endpoint, is planned to support drug registration in the U.S. and Europe.
Treatment with Batten-1 (miglustat) has shown potential in preserving vision in individuals with juvenile Batten disease (搜索), according to recent findings from an open-label Phase 1/2 study and expanded access program. Theranexus, the company developing Batten-1, reported that patients treated with the small molecule for 18 months and continuing treatment outside the study showed no signs of worsening vision, a common symptom of the disease.
Phase 1/2 Study and Expanded Access Program
All patients completed the Phase 1/2 study (NCT05174039), sponsored by the Beyond Batten Disease Foundation (BBDF), and opted to continue taking Batten-1 as oral capsules through an expanded access program. After two years of use, the treatment remained safe and well-tolerated, with case reports suggesting a possible stabilization of visual acuity, according to a press release from the Batten foundation.
"These case reports on visual acuity, in conjunction with other personal positive observations on visual experience in younger patients," add to evidence supporting Batten-1 as a possible disease-modifying therapy, said Gary Clark, MD, the study’s principal investigator at Texas Children’s Hospital in Houston.
Planned Phase 3 Trial
Based on the Phase 1/2 safety data, both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved the design of a Phase 3 trial. Theranexus has also launched an offering to fund the planned study, which will test a liquid formulation of Batten-1 considered more suitable for young patients.
"Our positive Phase 1/2 study, as well as very promising additional case reports of expanded use of miglustat with positive outcome on vision, strongly support the launch of our [Phase 3 trial], as well as the selection [of] visual acuity as primary endpoint," said Mathieu Charvériat, PhD, Theranexus’ CEO and chairman.
The planned Phase 3 clinical trial will be pivotal, "aimed at supporting the drug’s registration [approval] in the U.S. and Europe," Theranexus stated in the release.
About Juvenile Batten Disease
Juvenile Batten disease (搜索), also known as CLN3 disease, is caused by mutations in the CLN3 gene, which provides instructions for producing a protein called battenin. This protein is involved in various cellular processes, including breaking down and recycling unneeded molecules. The disease often leads to legal blindness by age 12.
When battenin is faulty or missing, aggregates of fatty molecules build up in lysosomes, the structures inside cells where unneeded molecules are broken down and recycled. Nerve cells are particularly vulnerable to this buildup.
Mechanism of Action
Batten-1 acts by preventing the enzyme glucosylceramide synthase (搜索) from working. This enzyme is involved in the production of certain fatty molecules. By blocking the enzyme, Batten-1 is expected to reduce the buildup of fatty aggregates and slow or prevent disease symptoms.
Phase 1/2 Study Details
The Phase 1/2 study enrolled six adolescents and adults, with an average age of 18.8 years (five males and one female), who were treated with Batten-1 as oral capsules at a maximum 600 mg dose every day for up to 104 weeks, or about two years.
Common side effects reported by all patients included diarrhea and weight loss. Two patients experienced a lesser appetite, muscle weakness, and low platelet counts. No serious treatment-related side effects were reported.
At 12 months, "physical assessment scores do not show expected [disease] progression," the researchers noted. In addition to keeping motor symptoms stable for at least 18 months, Batten-1 treatment appeared to stabilize vision with juvenile Batten disease (搜索), according to case reports on access program patients.