Published in Pipeline

Ocugen doses first patient in phase 3 RP gene therapy trial

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Ocugen, Inc. has dosed its first patient in the phase 3 liMeliGhT clinical trial for OCU400—an investigational candidate for the treatment of retinitis pigmentosa (RP) associated with rhodopsin (RHO) mutations.

Let’s start with OCU400.

OCU400 is a modifier gene therapy candidate based on NR2E3—a nuclear hormone receptor (NHR) gene.

Its intended purpose: To regulate physiological functions within the retina by delivering an adeno-associated viral (AAV) vector via subretinal injection.

Which would lead to: OCU400 may reset the affected/altered gene cell networks as well as reestablish 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 RHO mutations and Leber Congenital Amaurosis (LCA).

Any other regulatory updates to know of for this candidate?

Just a few …

  • December 2023: OCU400 was granted a Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA.
    • Designation was based on a phase 1/2 trial evaluating OCU400 among participants (aged 18 to 77) with RP associated with NR2E3 and RHO mutations (more on that in a moment)
  • April 2024: The FDA approved OCU400’s investigational new drug (IND) amendment for RP
    • Why this is important: The amendment enabled Ocugen to initiate this phase 3 trial (our topic of conversation)—a significant step that made OCU400 the first gene therapy candidate to enter into this clinical level with a broad RP indication.

Nice! Now before we get to this phase 3 trial, talk about that phase 1/2 study.

That multicenter, open-label, dose-ranging phase 1/2 study (NCT05203939) evaluated OCU400 at three dose levels:

  • 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

The findings?

Reported in April 2023, 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 multi-luminance mobility test (MLMT) score trend. See here for more info.


  • 89% of RP patients demonstrated preservation or improvement in the treated eye for one of the following scores from baseline: BCVA, low-luminance visual acuity (LLVA), or MLMT
  • 80% of RHO mutation participants experienced either preservation or improvement in MLMT scores from baseline
  • 78% of participants demonstrated preservation or improvement in treated eyes in MLMT scores from baseline

Note: The phase 1/2 study is slated to conclude in December 2024.

Alrighty, now let’s talk phase 3.

The multicenter, assessor-blinded, randomized phase 3 study (NCT06388200) is assessing the efficacy, safety, and tolerability of OCU400 among the following RP patients:

  • Participants (n = 150, estimated)
    • Criteria (see here for complete details):
      • Ages = 8+
      • Diagnosis:
        • RP associated with RHO mutations
        • Any other RP-associated mutation with a clinical phenotype of RP
      • Best-corrected visual acuity (BCVA) of ≤ 75 letters and ≥25 letters as measured by an Early Treatment Diabetic Retinopathy Study (ETDRS) chart

And the study setup?

Participants are being randomized 2:1 into groups to receive the following:

  • One arm of patients with the RHO gene mutation (n = 75)
    • 2.5 x 1010 vg/eye of OCU400
  • One arm of patients who are gene agnostic (n = 75)
    • Untreated control group

Study duration: 1 year

What’s being measured?

Two primary outcomes (with each measured at 52 weeks):

  • Participants with a change in functional vision in their study eye, as assessed via the Luminance Dependence Navigation Assessment (LDNA)
    • Note: LDNA is considered a “more sensitive and specific measurement of function” than MLMT—which was used in previous phase 3 trials, according to Ocugen.
  • Participants in the gene agnostic group with a change in functional vision in the study eye (also assessed via LDNA)

See here for secondary and other outcome measures.

When can we expect data from this?

Per Clinical Trials, the study is expected to conclude in October 2026 … but we’ll likely hear about interim results prior to then.

Down the road: As Ocugen previously reported, the company plans to use this phase 3 data to support a Biologics License Application (BLA) submission in 2026.

And the overall significance?

With no treatments currently available for RP patients diagnosed with gene-associated mutations, OCU400 represents a potentially groundbreaking therapeutic option that could “initiate a paradigm shift” within not just the RP field, but ophthalmology as a whole, according to Ocugen Retina Scientific Advisory Board Chair Lejla Vajzovic, MD, FASRS.

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