Ocugen Eyes 3 Retinal Gene Therapy Filings as Late-Stage Pipeline Advances

Key Points

• Ocugen plans three late-stage retinal gene therapy filings, targeting BLAs for retinitis pigmentosa and Stargardt disease next year and for geographic atrophy in 2028. The company says it aims to deliver two top-line readouts in 2025 and a third in geographic atrophy later on.
• The geographic atrophy program (OCU410) is moving into Phase 3 with a medium-dose selection based on Phase 2 data showing about a 33% reduction in lesion growth. Ocugen expects to enroll fewer than 300 patients in an adaptive trial designed with regulators in the U.S. and Europe.
• OCU410ST for Stargardt disease and OCU400 for retinitis pigmentosa are also advancing, with Stargardt’s pivotal study potentially supporting a BLA filing around mid-next year and retinitis pigmentosa top-line data expected in the first half of next year. Ocugen says its therapies are intended as one-time treatments across large patient populations.

Ocugen NASDAQ: OCGN outlined plans to advance three late-stage retinal disease programs, with company speaker Shankar saying the company is targeting biologics license applications for retinitis pigmentosa and Stargardt disease next year and a third BLA for geographic atrophy in 2028.

Speaking during a Piper Sandler discussion with analyst Biren Amin, Shankar said Ocugen is focused on inherited retinal diseases and dry age-related macular degeneration, including retinitis pigmentosa, Stargardt disease and geographic atrophy, the late form of dry AMD. He cited more than 100,000 retinitis pigmentosa patients in the U.S., about 50,000 Stargardt disease patients in the U.S. and 2 million to 3 million geographic atrophy patients in the U.S. and EU in the late stage of disease.

Shankar said Ocugen has retinitis pigmentosa and Stargardt programs in Phase 3 and expects to begin a global Phase 3 program for geographic atrophy in the third quarter, with alignment from regulators in the U.S. and Europe.

OCU410 Phase 3 Plans for Geographic Atrophy

Amin began by asking about OCU410, Ocugen’s gene therapy candidate for geographic atrophy. Shankar said the therapy uses a modified RORA gene, which Ocugen is also using in its Stargardt program. He said RORA is intended to regulate multiple pathways involved in disease progression, including oxidative stress, lipid metabolism, inflammation and the complement system.

Shankar contrasted the approach with currently approved therapies that target the complement system, saying Ocugen believes RORA could help “reset” cellular homeostasis and create a healthier environment for photoreceptors and retinal pigment epithelial cells. He said Phase 2 data showed treatment benefit in one year, while many trials in the disease area run for at least two years.

Discussing Phase 2 results, Shankar said the medium dose showed about a 33% reduction in lesion growth when using the square root measure, while the company observed a bell-shaped dose-response pattern rather than a linear one. He said the high dose did not perform as consistently as the medium dose, leading Ocugen to select the medium dose for Phase 3.

For the pivotal study, Shankar said Ocugen plans to use a baseline lesion size range of 2.5 mm squared to 17.5 mm squared, consistent with approved products, and will measure the rate of change in lesion size at four-month intervals through 12 months. He said the company expects to enroll fewer than 300 patients and plans an adaptive design in which a data monitoring committee may review the trial after 50% of patients complete one year.

Shankar said Ocugen designed the trial assuming an effect size lower than the Phase 2 result, using roughly 25% to build in a buffer. Secondary endpoints will include ellipsoid zone preservation and low-luminance visual acuity. He said the medium dose showed about 27% preservation of ellipsoid zone loss in Phase 2, and the company hopes to see results in the 20%-plus range.

On safety, Shankar said there were no serious adverse events related to the drug in Phase 2, though some surgery-related issues can occur with vitrectomy and most resolved.

Stargardt Program OCU410ST

Amin also asked about OCU410ST, Ocugen’s program for Stargardt disease. Shankar said Phase 1 results from the GARDian1 trial showed a 54% reduction in lesion growth in evaluable subjects compared with untreated eyes, using the contralateral eye as a control. He said the result informed the design of the Phase 2/3 pivotal study, which included 51 planned subjects, with 34 treated and 17 untreated.

Shankar said the company is also monitoring ellipsoid zone and low-luminance visual acuity as secondary measures. He said the program is intended as a one-time therapy and is being studied across a broad range of patients, including pediatric and adult patients aged three and older and patients from early to advanced stages of disease.

The GARDian3 pivotal trial includes an adaptive sample size re-estimation, which Shankar said is expected this quarter. He said the data monitoring committee could recommend no change, an adjustment in sample size or an extension of follow-up from 12 months to 16 months. Ocugen over-recruited the study to 63 patients, he said, potentially reducing the need for additional enrollment if the committee recommends a larger sample.

If no changes are made, Shankar said top-line results are expected in the second quarter of next year, followed by a BLA filing “a few weeks after that” or around mid-next year. If the timeline is extended, he said any delay could be roughly four to six months and still could allow the company to reach year-end next year. He also said no serious adverse events related to the drug have been observed so far in the Stargardt program.

OCU400 for Retinitis Pigmentosa

Ocugen’s third program, OCU400, targets retinitis pigmentosa. Shankar said enrollment is complete in the Phase 3 trial, with top-line data expected in the first half of next year. He described the trial as a large genetic medicine study with 140 patients and more than 25 genetic mutations represented.

Shankar said OCU400 uses NR2E3 delivered through an AAV vector and is designed to be gene-agnostic by upregulating key transcription factors and helping reset cellular function. He said the trial includes a 2:1 randomization ratio, with more patients in the treatment arm than the control arm, and covers a broad population that includes syndromic and non-syndromic retinitis pigmentosa.

The primary functional assessment will use a Luminance Dependent Navigation Assessment, which Shankar said is similar to the multi-luminance mobility test used in the approval of Luxturna but modified to be more specific and sensitive. He said the trial will compare the rate of improvement over one year against the control arm.

Upcoming Milestones

Shankar said Ocugen is aiming for two top-line readouts next year from its retinitis pigmentosa and Stargardt programs, followed by a third program readout in geographic atrophy in 2028. He reiterated the company’s goal of filing three BLAs over the next two years, followed by marketing authorization applications and potential global approvals.

“We’re going after with our one-time potential treatments, targeting hundreds of thousands to millions,” Shankar said, describing that as a key point of differentiation for the company.

About Ocugen NASDAQ: OCGN

Ocugen Inc is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing gene therapies to treat rare inherited retinal diseases, as well as vaccines designed to address unmet needs in infectious diseases. Headquartered in Malvern, Pennsylvania, the company applies its proprietary gene therapy platform to create novel treatments aimed at preserving and restoring vision, while leveraging strategic partnerships to broaden its vaccine pipeline.

In its gene therapy portfolio, Ocugen is advancing multiple programs targeting retinal disorders.

This instant news alert was generated by narrative science technology and financial data from MarketBeat in order to provide readers with the fastest reporting and unbiased coverage. Please send any questions or comments about this story to contact@marketbeat.com.