The FDA has cleared Ocugen, Inc. for its investigational new drug (IND) amendment to launch a phase 2/3 pivotal confirmatory clinical trial of its modifier gene therapy candidate for Stargardt disease.
First up, an Ocugen refresh.
The biotech company’s primary focus is on developing—and eventually commercializing—novel gene therapies, biologicals, cell therapies, and vaccines targeting major blindness diseases across the globe.
Among these ocular diseases: retinitis pigmentosa (RP); Leber congenital amaurosis (LCA); wet and dry age-related macular degeneration (AMD; geographic atrophy [GA]); diabetic macular edema (DME); diabetic retinopathy; and Stargardt.
- Check out its portfolio.
Real quick: What does an IND acceptance mean?
In general: An FDA-authorized IND application enables a sponsor (company) to conduct human clinical trials with an experimental drug or biological product
- Importantly: INDs are considered a critical step in the U.S. regulatory and approval process for new therapeutics.
Got it. Now zero in on this specific gene therapy.
The asset: OCU410ST.
What it is: An investigational modifier gene therapy dependent on Ocugen’s adeno-associated vector (AAV) delivery platform for the retinal delivery of the Retinoic acid-related orphan receptor α (RORA) gene.
- Specifically: It is one of several therapeutics in Ocugen’s gene therapy pipeline based on nuclear hormone receptor (NHR) RORA, which is responsible for regulating pathophysiological pathways and genes associated with Stargardt development.
- About NHR: These are transcription factors that bind with proteins to regulate gene expression, acting as “on-off” switches for cell differentiation, metabolism, and proliferation.
Expand on this Stargardt connection.
The disease develops as a result of mutations (changes) in the ATP-binding cassette subfamily A, member 4 (ABCA4) gene.
- In turn, these mutations lead to defective processing and transportation of all-trans retinaldehyde from photoreceptors to retinal pigment epithelium (RPE) cells.
How OCU410ST gets involved: The gene therapy regulates genes and pathways involved in the onset and progression of Stargardt.
Hold up … wasn’t this asset just in the news?
Indeed it was—just 2 weeks ago, in fact.
The reason: The FDA granted OCU410ST Rare Pediatric Disease designation (RPDD) for all types of Stargardt (ABCA4-associated retinopathies), as well as:
- RP 19 (RP19)
- Cone-rod dystrophy 3 (CORD3)
Plus, prior to this: The gene therapy received Orphan Drug designation (ODD).
Now before we get to this trial clearance, let’s talk clinical data so far.
Earlier this year, Ocugen reported positive 6-month findings from the multicenter, open-label, dosing-ranging phase 1/2 GARDian trial on OCU410ST as a unilateral subretinal injection in three doses for Stargardt.
The crux of the data: OCU410ST demonstrated a favorable safety and tolerability profile, with treated eyes displaying a 52% slower lesion growth from baseline versus untreated eyes
And more recently?
The company reported lesion growth continued to slow (48%) at the 12-month mark, along with a statistically significant (p=0.031) improvement and clinically meaningful, nearly 2-line gain in visual function (best-corrected visual acuity [BCVA]) among treated eyes when compared to untreated eyes.
Nice! So what’s the plan for the phase 2/3 trial?
A total of 51 Stargardt patients are expected to be enrolled, with:
- 34 (with poorer visual acuity) to receive a one-time injection of OCU410ST (200 μL at a concentration of 1.5 × 10¹¹ vector genomes/mL)
- 17 assigned to an untreated control group
And what will be measured?
The main goal: To determine the reduction in atrophic lesion size.
The secondary endpoints: Improvements in BCVA and low-luminance visual acuity (LLVA) versus controls.
When can we expect data?
No specific timeframe was released; however, the company did share that it plans to use 1-year findings from the study to support a Biologics License Application (BLA) submission to the FDA for marketing approval in 2027.
- Shankar Musunuri, PhD, MBA, Ocugen chairman, CEO, and co-founder, also stated that—with this phase 2/3 trial initiation—the company will be expediting “the clinical development of OCU410ST by 2 to 3 years and potentially providing an innovative gene therapy to patients desperate for a treatment option.”