Ocugen, Inc. received Rare Pediatric Disease Designation (RPDD) from the FDA for OCU410ST, its gene therapy candidate for the treatment of ABCA4-associated retinopathies, including Stargardt disease.
First, let’s talk RPDD.
This FDA-granted status RPDD is granted by the FDA for drugs under development for rare childhood diseases (affecting patients under the age of 18) when a few key criteria have been met.
- See those criteria here.
A major advantage to this: Companies granted RPDD are also eligible to (potentially) receive a Priority Review Voucher (PRV) after their therapeutic’s marketing approval.
- Even better: A PRV would accelerate the FDA review process—cutting it down to just six months from approximately 10—and would also be transferrable to another candidate in that company’s pipeline.
Nice! Next up: Stargardt.
As one of the most common inherited single-gene retinal diseases with no approved treatment, Stargardt is commonly associated—among other symptoms—with a slow loss of central vision in both eyes.
Its cause: Changes (mutations) in the ATP-binding cassette subfamily A, member 4 (ABCA4) gene, which affects how the body uses Vitamin A, and follows an autosomal recessive pattern of inheritance.
- In turn, these mutations lead to defective processing and “transportation of all-transretinaldehyde from the photoreceptors to retinal pigmental epithelium (RPE) cells.”
The patients: The disease is sometimes referred to as juvenile macular dystrophy (degeneration) because it primarily affects pediatric patients and young adults under the age of 18.
Now to Ocugen’s candidate.
OCU410ST is an investigational modifier gene therapy that utilizes Ocugen’s adeno-associated vector (AAV) delivery platform for the retinal delivery of the Retinoic acid-related orphan receptor α (RORA) gene.
The candidate is one of several therapeutics in Ocugen’s modifier gene therapy pipeline based on nuclear hormone receptor (NHR) RORA—responsible for regulating pathophysiological pathways and genes (including ABCA4) associated with the development of Stargardt disease.
- 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.
Is it under clinical investigation for any other retinal diseases?
Indeed it is. In fact, the FDA’s RPDD was for ABCA4-associated retinopathies that included Stargardt and:
- Retinitis pigmentosa 19 (RP19)
- Cone-rod dystrophy 3 (CORD3)
Even further: OCUF410ST was previously granted Orphan Drug Designation (ODD) for those three retinopathies as well.
Gotcha. So has the therapeutic undergone any clinical evaluations yet?
It has, and plans are underway for another upcoming clinical study.
But first: OCU410ST was most recently evaluated in the two-part, multicenter, open-label, dose-ranging phase 1/2 GARDian trial, which analyzed the safety and efficacy of a unilateral subretinal administration of OCU410ST (in three dose levels) among Stargardt patients.
- The findings, as of the 6-month follow-up:
- OCU410ST demonstrated a favorable safety and tolerability profile
- No OCU410ST-related serious adverse events (AEs) were observed
- Treated eyes had 52% slower lesion growth from baseline versus untreated eyes at the 6-month follow-up
- A clinically meaningful 2-line (10-letter) improvement was observed for best-corrected visual acuity (BCVA) among treated eyes (p = 0.023 statistical significance)
Sounds promising! And what’s up next?
In late February 2025, Ocugen announced plans (after FDA consultation) to move forward with a phase 2/3 pivotal confirmatory clinical trial of OCU410ST.
The intent: If positive, the findings from this trial would be the foundation for a potential Biologics License Application (BLA) submission.
What do we know so far about this trial?
A total of 51 participants will be randomized, of which:
- 34 are expected to receive a single, subretinal, 200-μL injection of OCU410ST (concentration level: 1.5 x 1011 vg/mL) in the eye with worse visual acuity
- 17 will serve as untreated controls
The primary endpoint: Change in atrophic lesion size
The secondary endpoints: Visual acuity (measured via BCVA) and low luminance visual acuity [LLVA] of OCU410ST-treated versus untreated patients.
And the timeframe for this?
Ocugen plans to initiate this trial within “the next few weeks.”
- One-year data is expected to be used in its anticipated BLA filing in 2027.
And keep in mind: Thanks to the FDA granting RPDD and ODD to OCU410ST, its clinical development pathway toward approval can be expedited by 2 to 3 years, Chief Medical Officer Huma Qamar, MD, MPH, previously stated.