The FDA has granted a Regenerative Medicine Advanced Therapy (RMAT) designation to Ocugen, Inc.’s OCU400, an investigational candidate for retinitis pigmentosa (RP) associated with rhodopsin (RHO) mutations.
Refresh me on RMAT.
The FDA’s RMAT designation is part of a dedicated program designed to expedite the development and review process of investigational drug candidates intended to treat, modify, reverse, or cure a serious or life-threatening condition. The designation is based on preliminary clinical evidence that indicates the specific therapy could potentially address an unmet need for the condition.
Now OCU400.
The novel gene therapy candidate which consists of a functional copy NR2E3 delivered to target retinal cells via a subretinal injection leveraging an adeno-associated viral (AAV) vector.
And NR2E3 is …?
NR2E3 is an epigenetic regulator, or nuclear hormone receptor (NHR) gene—which regulates physiological functions within the retina..
So what is OCU400 intended to do?
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.
Important to know: the FDA granted OCU400 Orphan Drug designation in December 2022 for both RP and Leber Congenital Amaurosis (LCA).
Gotcha. So what was this RMAT designation based on?
Per Ocugen, preliminary results from the multicenter, open-label, dose-ranging phase 1/2 study (NCT05203939) that examined the use of OCU400 in 18 participants (aged 18 to 77) with RP associated with NR2E3 and RHO mutations:
- 10 patients in the dose escalation phase
- 8 patients in the expansion phase
To note, the trial was also expanded to include LCA participants with the CEP290 gene mutation and pediatric patients with the NR2E3, RHO, and CEP290 mutations.
And the dosage levels?
A total of three patient cohorts received three levels of doses (vg/mL*):
- Cohort 1: up to 1.66 x 1010 vg/mL (low dose)
- Cohort 2: up to 3.33 × 1010 vg/mL (mid dose)
- Cohort 3: up to 1.66 × 1011 vg/mL (high dose)
*vg= viral genomes
What’s being measured?
The secondary outcome measures included:
- Low-luminance visual acuity (LLVA)
- Best-corrected visual acuity (BCVA)
Another notable outcome measured in the study was Multi-luminance mobility testing (MLMT).
Findings so far?
Preliminary 9-month data of cohort 1 indicated a favorable safety profile and visual improvements in OCU400-treated patients, with 100% demonstrating a stable or improved MLMT score trend. See here for further details, reported in April 2023.
So what’s next?
The company is currently working with the FDA to finalize phase 3 protocols for advancing the clinical development of OCU400 to potentially “support an application for marketing authorization.”
According to Clinical Trials, the ongoing 12-month phase 1/2 trial—is expected to conclude by December 2024.
Stay tuned for the data readout from cohorts 2 and 3 in the meantime!