Panelists at the H.C. Wainwright Sixth Annual Ophthalmology Virtual Conference said investigational therapies for inherited retinal disorders could begin to reshape treatment options for Stargardt disease and retinitis pigmentosa, two conditions with limited or no approved treatment choices today.
The discussion featured Dr. Ahmad Al-Moujahed, Assistant Professor of Ophthalmology at Stanford University School of Medicine; Dr. Hendrik Scholl, Chief Medical Officer of Belite Bio (NASDAQ:BLTE); and Dr. Samarendra Mohanty, President, Chief Scientific Officer and Co-Founder of Nanoscope Therapeutics.
Stargardt Disease Focuses on Slowing Structural Damage
For Stargardt disease, the panel emphasized that functional benefits can be difficult to demonstrate in short clinical trials because the disease progresses slowly. Al-Moujahed said researchers often look to structural preservation, such as slowing lesion growth, with the expectation that it may translate into long-term preservation of visual function.
Scholl said Belite Bio’s DRAGON trial showed a 35.7% reduction in annualized macular lesion growth. He described the effect as “substantial,” comparing it with lesion-growth reductions reported in pivotal trials of complement inhibitors for geographic atrophy. Scholl said definite decreased autofluorescence, or DDAF, is associated with complete degeneration of retinal pigment epithelium and photoreceptors, and that preserving photoreceptors should eventually translate into clinical benefit.
Asked why visual acuity changes were minimal in both arms over 24 months, Scholl said visual acuity declines too slowly in Stargardt disease to be a practical endpoint over a short trial period. He cited prior ProgStar data showing average visual acuity decline of about 0.55 ETDRS letters per year.
Scholl said all patients in DRAGON had DDAF at baseline and almost all had foveal involvement. He said Belite Bio did not identify a specific dependency on ABCA4 genotype, adding that more than 2,800 pathogenic ABCA4 mutations are known and that patients typically carry two mutations.
On timing of treatment, Scholl said DRAGON enrolled patients with established lesions because the trial needed a reliable approval endpoint. However, he said patients with earlier disease could potentially benefit most because they have more remaining photoreceptors to preserve, while even patients at the U.S. legal blindness level may benefit if additional loss can be slowed.
Safety and Monitoring for Tinlarebant
Scholl said tinlarebant’s safety profile in DRAGON was manageable. He said six serious adverse events were reported in the study, four in the placebo group, and all were non-ocular. Ocular events such as delayed dark adaptation, xanthopsia and night vision impairment were consistent with the drug’s anticipated pharmacologic effects, he said, and most events were mild and resolved while patients remained on study.
Scholl said delayed dark adaptation is also a symptom of Stargardt disease itself. At month 25, he said, both tinlarebant and placebo groups showed only small changes from baseline in measured dark adaptation time. He said xanthopsia refers to a temporary yellowish discoloration of the visual scene during light adaptation and would require patient education if the drug is approved.
For routine practice, Scholl said six-month retinal imaging visits could be reasonable if tinlarebant becomes available. He said frequent RBP4 or vitamin A monitoring is likely unnecessary in his view, and that DRAGON did not show an effect on liver health.
Nanoscope Highlights Restorative Approach in Advanced RP
Mohanty described Nanoscope’s MCO-010 as an optogenetic therapy targeted to inner retinal cells, including bipolar cells, that remain after photoreceptor loss in retinitis pigmentosa. He said vision in advanced RP is not defined only by best-corrected visual acuity, but also by visual field, mobility, shape discrimination and daily functioning.
Mohanty said patients in Nanoscope trials improved across measures including BCVA, mobility and shape discrimination, and that all treated patients improved on at least one of three key efficacy assessments. He said some patients who could not be measured effectively using a standard visual acuity tool still showed improvement in mobility or shape discrimination.
Asked whether improvements translate into real-world function, Mohanty said patients have reported gains in activities such as recognizing people, cooking, finding objects on a table and retrieving items from a refrigerator. He said some patient-reported outcomes correlated with BCVA, mobility and shape discrimination testing.
Mohanty said preserved optic nerve function is necessary for response because signals must be transmitted from the eye. He said patients in Nanoscope studies included retinas as thin as 60 microns and as thick as several hundred microns, and that thicker retinas may respond better because they may contain more bipolar cells.
On durability, Mohanty said Nanoscope currently has nearly four years of data from 35 dosed patients across trials and expects to have five-year data by the time of launch. He said the company believes the AAV-based expression in post-mitotic cells could last for a long period, though real-world evidence would be needed for confirmation.
Commercial and Regulatory Milestones
Scholl said Belite Bio is awaiting the FDA’s Day 74 letter following its NDA submission, which would communicate filing acceptance, provide a PDUFA date and shape the remainder of the review. He said the company believes it may receive Priority Review because tinlarebant has Breakthrough designation.
Scholl also said Belite Bio is studying tinlarebant in geographic atrophy through the PHOENIX trial, which has 530 patients. He said the company is nearing availability of 12-month data for all patients and has not yet decided whether to conduct an interim analysis for sample size re-estimation. He said the trial is expected to complete at the beginning of the third quarter of next year.
Mohanty said Nanoscope’s upcoming milestones include BLA acceptance, a Day 74 letter and a PDUFA date. He also cited planned randomized controlled trials in Stargardt disease and geographic atrophy, as well as regulatory activity outside the U.S., including Japan.
On commercialization, Scholl said Belite Bio is focused on genetic testing education, reimbursement discussions and patient education. He estimated U.S. Stargardt prevalence at roughly 50,000 to 55,000 patients, while noting inherited retinal diseases remain underdiagnosed.
Mohanty said Nanoscope’s initial U.S. focus is RP patients who are legally blind or worse, while broader indications may be pursued outside the U.S. He said the company is seeking acceptance of not requiring genetic testing, arguing that many RP patients do not yet have confirmed pathogenic mutations.
Physician Adoption and Patient Access
Al-Moujahed said he would discuss both therapies with patients if they become available, while explaining the reported benefits, potential side effects and the need for monitoring. For an oral therapy, he said he might initially see patients at three months to assess tolerability before extending follow-up intervals. For gene therapy, he said he would likely start with the worse-seeing eye and proceed cautiously.
Al-Moujahed identified reimbursement as a key practical concern for physicians, especially if the therapies are expensive. He said physicians may have sufficient patient populations and treatment expertise, but will need payer coverage processes to be manageable.
Looking ahead, Al-Moujahed said the inherited retinal disease field is entering “an exciting time,” with advances in disease-modifying therapies and vision restoration approaches. He said he expects patients could have several additional approved treatment options within a few years.
About Belite Bio (NASDAQ:BLTE)
Belite Bio, Inc (NASDAQ: BLTE) is a clinical-stage biotechnology company focused on discovering and developing small molecule therapeutics for metabolic and inflammatory diseases. Leveraging a proprietary drug-discovery platform, the company aims to address conditions such as nonalcoholic steatohepatitis (NASH) and obesity by targeting pathways involved in fibrosis, inflammation and metabolic regulation.
Belite Bio’s pipeline includes multiple candidates in preclinical and early clinical development stages.
