Ocugen, Inc. announced the FDA has approved its investigational new drug (IND) amendment for OCU400, its modifier gene therapy product, for the treatment of retinitis pigmentosa (RP).
Let’s start with this investigational candidate.
OCU400 is based on NR2E3—a nuclear hormone receptor (NHR) gene—intended to regulate physiological functions within the retina by delivering an adeno-associated viral (AAV) vector via subretinal injection.
The thought: OCU400 may help to reset the affected/altered gene cell networks along with reestablishing retinal homeostasis, potentially stabilizing cells and rescuing compromised photoreceptors from degenerative processes.
Note: OCU400 was granted Orphan Drug designation by the FDA in December 2022 for both RP associated with rhodopsin (RHO) mutations and Leber Congenital Amaurosis (LCA).
And most recently?
The candidate was also granted a Regenerative Medicine Advanced Therapy (RMAT) designation in December 2023.
Refresh: RMAT designation is part of the FDA’s dedicated program designed to expedite the development and review process of investigational drug candidates that are intended to treat, modify, reverse, or cure a serious or life-threatening condition.
Note: The designation is based on preliminary clinical evidence that indicates the specific therapy could potentially address an unmet need for the condition.
Gotcha. Now talk about this amendment.
This latest development paves the way for Ocugen to initiate a phase 3 trial on OCU400—making it the first gene therapy candidate to enter into this level with a broad RP indication, according to the company’s chairman, CEO, and co-founder Shankar Musunuri, PhD, MBA.
And this trial?
Per the company, the study will seek to enroll 150 participants who will be randomized 2:1:
- One arm of 75 participants with the RHO gene mutation
- 2.5 x 1010 vg/eye of OCU400
- One arm of 75 participants who are gene agnostic
- Untreated control group
So what will be measured?
The primary outcome measure will be an updated mobility course called the Luminance Dependent Navigation Assessment (LDNA), which will include a wider range of:
- Light intensity (0.04-500 Lux)
- Lux Levels (0-9)
- Uniform correlation between Lux level and Lux intensity
Arun Upadhyay, PhD, Ocugen’s chief scientific officer (CSO), noted that the LDNA sensitive mobility course was developed via a collaboration between the company and the FDA in order for the study to enroll patients with early to advanced stages of RP.
And the expectation for this?
Dr. Upadhyay stated that the company expects for the study to result in more than 50% of intent-to-treat RHO patients meeting “the responder criteria, which is demonstrating 2 or greater Lux level of improvement after one year of treatment based on phase 1/2 study results.”
About that previous phase 1/2 data…
We’ll give you the rundown:Reported in April 2023, the multicenter, open-label, dose-ranging study (NCT05203939) enrolled 18 RP patients (ages 18 to 77) with RHO and NR2E3 gene mutations—plus 10 patients in the dose escalation and 8 patients in the expansion phase.
The study was also expanded to include:
- LCA patients with the CEP290 gene mutation
- Pediatric patients with the following mutations:
- NR2E3
- RHO
- CEP290
See here for the three levels of dosing details (low, medium, and high) for OCU400, which was divided among three patient cohorts.
What was measured?
A different mobility test strategy: the multi-luminance mobility test (MLMT) and best-corrected visual acuity (BCVA).
Those preliminary findings: A favorable safety profile was indicated for OCU400, along with visual improvements following treatment in seven patients.
Our coverage of these results can be found here.
When can we expect the complete findings from that study?
Per Clinical Trials, the phase 1/2 study is being conducted in two phases—enrolling a total of 124 participants: 24 in OCU400-101 and 100 in OCU400-104.
The study’s estimated completion is slated for December 2024 … so stay tuned for more data in the near future.
And circling back to this phase 3 study… what’s next?
With the initiation of this study, the company reports that “OCU400 remains on track for the 2026 biologics license application (BLA) approval target.”
Clinical data will likely be reported before then as well.