Ocugen, Inc. has released positive preliminary safety and efficacy results from the phase 1/2 trial of OCU400 for the treatment of inherited retinal diseases (IRDs) such as retinitis pigmentosa (RP) and Leber Congenital Amaurosis (LCA).
Refresh me on OCU400.
As a novel gene therapy product candidate, OCU400 is based on NR2E3—a nuclear hormone receptor (NHR) gene—that regulates physiological functions within the retina by delivering an adeno-associated viral (AAV) vector by subretinal injection.
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.
Of note, the FDA granted OCU400 Orphan Drug designation in December 2022 for both RP and LCA.
Didn’t we just hear about OCU400?
Indeed. Two weeks ago, the FDA approved Ocugen’s request to enroll pediatric patients in its RP/LCA gene therapy trial.
Now talk about this trial.
The multicenter, open-label, dose-ranging study (NCT05203939) enrolled 18 RP patients (ages 18 to 77) with rhodopsin (RHO) and NR2E3 gene mutations—10 patients in the dose escalation and 8 patients in the expansion phase.
Investigators also expanded the trial to include LCA patients with the CEP290 gene mutation as well as pediatric patients with the NR2E3, RHO, and CEP290 mutations.
What are the levels of dosage?
Three cohorts of patients received three level 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 was the preliminary data on?
Nine-month follow-up analysis for cohort 1 (3 patients) and 6-month follow-up data for 4 patients (1 from cohort 1; 3 from cohort 2) were assessed.
Findings?
Measuring with multi-luminance mobility testing (MLMT) and best-corrected visual assessment (BCVA), results indicated a favorable safety profile and visual improvements following OCU400 treatment in 7 patients.
Give me some numbers.
Key outcomes included 100% of patients demonstrating a stable or improved MLMT score trend. Further, 5 out of 7 (71.4%) OCU400-treated eyes showed a 1+ Lux level improvement in MLMT score versus 2 out of 7 (28.6%) for untreated eyes.
What else?
In cohort 1, 9-month follow-up of 2 out of 3 OCU400-treated patient eyes (66.7%) showed a 2+ Lux level improvement in MLMT score compared to none of the untreated eyes; and an 8-11 letters of improvement in BCVA score were observed in 3 out of 7 (42.9%) of OCU400-treated eyes (compared to none in untreated eyes).
What’s next?
Ocugen plans to continue monitoring long-term safety and efficacy data on the study patients. According to Clinical Trials, the study is slated to complete by February 2024.