Oculis S.A. reported topline data from the phase 2b Randomized Evaluation of Licaminlimab's Efficacy and Safety for Dry Eye Disease (RELIEF) trial evaluating OCS-02, a biologic eye drop, for the treatment of dry eye disease (DED).
First, a rundown on Oculis.
The Switzerland-headquartered global clinical-stage biopharmaceutical company—with U.S. operations in Boston, Massachusetts—is developing novel topical treatments for such ophthalmic diseases as:
- Dry eye (our topic of interest)
- Retina
- Neuro-ophthalmology
See here for a look at its pipeline and clinical updates, including for:
- OCS-01 for diabetic macular edema (DME) and inflammation post-cataract surgery
- Lead investigational candidate
- OCS-05 for glaucoma, diabetic retinopathy (DR), geographic atrophy (GA) and neurotrophic keratitis (NK)
Now OCS-02.
OCS-02 (60 mg/mL licaminlimab ophthalmic suspension), a new anti-TNFα antibody fragment for topical ocular application, is based on a proprietary single-chain antibody fragment (scFv) technology.
Explain this technology.
With Oculis’s antibody fragment technology, the lower molecular weight of the fragment (in relation to a whole antibody) allows for the development of a higher formulation concentration that advances ocular tissue penetration.
The result: scFv is more equipped for topical ocular treatment of the ocular surface (such as in DED) or the anterior chamber full-length antibodies.
And the OCS-02 connection: OCS-02 is formulated to bind to and neutralize human TNFα activity.
Gotcha. Now back to explaining OCS-02.
Its dual mechanism of action (MOA) features both anti-inflammatory and anti-necrosis that have already been clinically proven with other anti-TNFα antibodies as a systemic treatment for multiple inflammatory ocular diseases.
- Plus: It’s also in clinical development for uveitis (see below).
Talk about this clinical data.
To be clear: Published in Translational Vision Science & Technology in 2022, the data on this eye drop is in regards to its efficacy for a different ocular condition: acute anterior uveitis (AAU).
Those findings: OCS-02 was well tolerated in participants when dosed (eight drops/day of 60 mg/mL for 15 days, then four drops/day for seven days).
- Plus: The study met its primary objective of a clinical response of ≥2-step decrease in anterior chamber (AC) cell grade at day 15. See the full study details and findings here.
That sounds promising … next: refresh me on this phase 2b trial.
Conducted in collaboration with ORA, Inc., the phase 2b study is a multicenter, randomized, double-masked, active-control study (NCT05896670) assessing the safety and efficacy of OCS-02 (vs. a placebo), both in eye drop form, randomized 1:1 for DED.
- The participants: 122 patients (aged 18+) with moderate-to-severe DED
- The doses:
- OCS-02 (60 mg/mL licaminlimab); three times a day (TID) for six weeks
- n = 62
- OCS-02 vehicle; TID for six weeks
- n = 60
- OCS-02 (60 mg/mL licaminlimab); three times a day (TID) for six weeks
Note: Patients in both eye drop groups were also assigned artificial tears (TID) for two weeks.
And as a bonus: Efficacy and safety of OCS-02 administered to a subset of 23 participants carrying a specific TNFR1-related genotype were also evaluated.
What did the study measure?
Primary outcome: Efficacy of OCS-02 for DED via patients’ total corneal staining, as measured by the change from baseline vs vehicle at:
- Pre-controlled adverse environment (CAE)
- Pre-CAE to post-CAE
- Post-CAE
Time period: Baseline to Day 43Measurements taken at: Baseline, Day 15, and Day 43
Now this topline data.
Oculus reported a favorable treatment effect for OCS-02 was observed in multiple sign endpoints, including fluorescein staining in the:
- Total cornea
- Inferior corneal
- Central corneal
- Nasal conjunctival
- Total conjunctival
- Total ocular surface regions
- Schirmer’s test
- Conjunctival redness
How did OCS-02 impact corneal inflammation?
By as early as Day 15, a “rapid and favorable treatment effect” was noted among the TNRF1 subgroup participants, growing to a significantly favorable effect by Day 43.
This was measured via the difference in mean change from baseline vs vehicle for inferior corneal fluorescein staining (CFS) score: -0.59 (Confidence interval [CI]: -1.165, -0.017).
Plus: The effect continued to increase over time.
Any adverse events?
While OCS-02 was well tolerated in general, mild and transient ocular treatment-emergent adverse events (TEAEs) were observed in:
- 11.5% of OCS-02 group participants
- 19.2% of vehicle group participants
Note: These TEAEs were similar in both the study and fellow eyes.
Also: No serious ocular AEs were associated with OSC-02.
This sounds promising! So what’s next?
According to Oculis CEO Riad Sherif, MD, the company is looking to discuss with the FDA plans advancing the OCS-02 clinical program to a phase 3 stage.
The plan: Conducting an end-of-phase 2 meeting and finalizing the phase 3 development plan.
And the overarching significance?
With OCS-02’s dual MOA—not to mention these promising findings on its effect for corneal inflammation—the eye drop represents a potentially groundbreaking paradigm shift in targeting and treating the root of DED