Belite Bio’s Tinlarebant Studied to Treat Childhood-onset Stargardt Disease

Belite Bio presented final data from a 24-month, phase 2 study of Tinlarebant (LBS-008) in adolescent Stargardt disease (STGD1). The study—LBS-008-CT02—enrolled 12 adolescent STGD1 patients, aged 12-18 years, who completed the 24 months of treatment. Belite Bio’s Tinlarebant is an orally administered tablet intended to slow disease progression in patients affected with STGD1 and geographic atrophy (GA) in advanced dry age-related macular degeneration (Dry AMD).

Professor John Grigg, MBBS, MD, who is the study’s principal investigator, presented the final study data at AAO 2023, the 127th annual meeting of the American Academy of Ophthalmology, held November 3-6 in San Francisco, California.

Professor Grigg is Head Specialty of Ophthalmology at the University of Sydney and Consultant Ophthalmologist at the Sydney Children’s Hospitals Network at Westmead and Sydney Eye Hospital in Sydney, Australia.

“We are very encouraged by the promising 24-month treatment final results from this phase 2 study,” commented Prof. Grigg in Belite Bio’s press release. “The natural progression of childhood-onset STGD1 is characterized by a rapid visual decline and fast disease progression leading to permanent visual loss at a very young age. We are pleased that the phase 2 final data continued to demonstrate the slowing of disease progression in the study cohort and stabilization of several structural and functional parameters, including stabilization of visual acuity.”

As outline by the company, the key study findings include the following:

• Tinlarebant was safe and well-tolerated with no withdrawals due to adverse events through the 24-month study period.
• Retinal imaging showed that five of 12 patients (42%) remained free of atrophic retinal lesions (ie, definitely decreased autofluorescence [DDAF]) after 24 months of Tinlarebant treatment.
• A comparison of the 24-month DDAF lesion growth between Tinlarebant-treated patients and patients in the ProgSTAR studies possessing similar baseline characteristics (aged ≤ 18 years) showed a sustained lower DDAF lesion growth in the Tinlarebant group over the 24-month treatment period (P < .001).
• Visual acuity was stabilized in the majority of patients during the study with a mean loss of five letters after 24 months of treatment (a loss of < 10 letters is not considered clinically significant).

A copy of the AAO presentation slides is available through the company online here.

Additionally, the company advised that full enrollment of 104 patients in the DRAGON study is complete. The global, phase 3 DRAGON is a 2-year, multicenter, randomized, double-masked, placebo-controlled study to evaluate the safety and efficacy of Tinlarebant in the treatment of STGD1 adolescent patients. One-year interim data are expected in mid to late 2024.

Tom Lin, MMed, PhD (Med), who is Chairman and CEO of Belite Bio, discussed the implications of the results in the company press release.

“Tinlarebant’s final phase 2 results represent a significant milestone for Belite Bio and provide additional foundational support for the work being conducted across our trials,” commented Dr. Lin. “The final phase 2 data continue to demonstrate Tinlarebant’s safety profile and show a sustained lower DDAF lesion growth compared to ProgSTAR participants over the 2-year treatment period.”

Dr. Lin added, “We hope to see similar data in the ongoing phase 3 DRAGON study, further supporting Tinlarebant as a promising oral treatment for STGD1 patients.”

According to the company’s press release, Tinlarebant is intended to reduce the accumulation of the vitamin A-based toxins, bisretinoids, that cause retinal disease in STGD1 and also contribute to disease progression in GA, or advanced Dry AMD. Tinlarebant works by reducing and maintaining levels of serum retinol binding protein 4 (RBP4), the sole carrier protein for retinol transport from the liver to the eye. By modulating the amount of retinol entering the eye, Tinlarebant reduces the formation of bisretinoids.

Tinlarebant has been granted Fast Track Designation and Rare Pediatric Disease designation in the United States, and Orphan Drug Designation in the United States and Europe for the treatment of STGD1, advised Belite Bio.

Belite Bio also advised it intends to evaluate safety and efficacy of Tinlarebant in GA patients in the 2-year, phase 3 PHOENIX study.