Clearside Biomedical, Inc. (Nasdaq: CLSD), a biopharmaceutical company revolutionizing the delivery of therapies to the back of the eye through the suprachoroidal space (SCS®), announced today positive results from the Extension Study of its OASIS Phase 1/2a clinical trial of CLS-AX (axitinib injectable suspension) administered by suprachoroidal injection via Clearside’s SCS Microinjector® in neovascular age-related macular degeneration (wet AMD) participants. These results include the final six-month data from all participants in the Extension Study and augment the previously reported 3-month results and interim extension data.
Thomas A. Ciulla, M.D., M.B.A., Chief Medical Officer and Chief Development Officer, said, “The positive data from our OASIS Extension Study reinforces our belief that CLS-AX has the potential to reduce treatment burden in patients with wet AMD while maintaining stable visual acuity. In all participants in the trial, CLS-AX was well tolerated and demonstrated an excellent safety profile across all timepoints and doses. Importantly, the full extension data reported today showed promising durability with 67% of participants going at least six months without additional treatment, and 50% of participants going beyond six months. With these favorable data, we are actively preparing for and expect to initiate a randomized, controlled, double-masked, Phase 2b clinical trial, called ODYSSEY, in the first quarter of this year, with the primary endpoint readout anticipated in mid-2024.”
George Lasezkay, Pharm.D., J.D., Clearside’s President and Chief Executive Officer, commented, “We made tremendous progress in 2022 with the commercialization of our first suprachoroidal product by Bausch + Lomb and the positive safety and durability results from our Phase 1/2a OASIS trial. As we advance our CLS-AX wet AMD program with the initiation of our ODYSSEY Phase 2b trial, we continue to build on this significant momentum and will further increase awareness of the broad potential in delivering therapies to the back of the eye using our proprietary SCS® platform technology.”
“This CLS-AX data demonstrating stable visual acuity with durability up to and beyond six months is very encouraging as we look to lower the treatment burden for wet AMD patients. As the management of wet AMD expands to include therapeutic options with different mechanisms of action, such as axitinib and faricimab, it makes sense to compare outcomes to these therapies in future clinical trials. CLS-AX, with suprachoroidal delivery and an alternate mechanism of action from standard of care anti-VEGF products, may prove to be a differentiated therapy for wet AMD and other retinal diseases,” added Mark R. Barakat, M.D., Director of Retinal Research Institute, Retinal Consultants of Arizona, and Clinical Assistant Professor of Ophthalmology, University of Arizona College of Medicine - Phoenix.
Conference Call & Webcast Details
Clearside will host a webcast and conference call with accompanying slides today at 8:30 a.m. ET, including comments by management and retinal expert, Dr. Mark R. Barakat. The live and archived webcast may be accessed on the Clearside website under the Investors section: Events and Presentations. The live call can be accessed by dialing (888) 506-0062 (domestic) or (973) 528-0011 (international) and entering conference code: 676850.
OASIS Data Summary
The OASIS Phase 1/2a trial is complete for both the 3-month dose-escalation portion and the 3-month Extension Study. The study included four cohorts at the following doses: Cohort 1 at 0.03 mg; Cohort 2 at 0.1 mg; Cohort 3 at 0.5 mg; Cohort 4 at 1.0 mg. Participants from Cohorts 2, 3 and 4 who rolled over into the Extension Study were followed for a total of 6 months after a single dose of CLS-AX. Participants enrolled in OASIS were heavily anti-VEGF treatment experienced with active disease1 at screening, which was confirmed by an independent reading center.
Safety and Tolerability Results in All Cohorts in the 3-Month Study (n=27) & 6-Month Extension Study (n=14)
- No serious adverse events (SAEs), no treatment emergent adverse events (TEAEs) related to study treatment, and no dose limiting toxicities.
- No adverse events related to inflammation, vasculitis or vascular occlusion.
- No vitreous “floaters” or dispersion of CLS-AX into the vitreous.
- No retinal detachments, endophthalmitis, or adverse events related to intraocular pressure.
Durability in the 6-Month Extension Study in Cohorts 3 & 4 at higher doses (n=12)
- 77% - 85% reduction in treatment burden was observed compared to the average monthly injections in the six months before CLS-AX administration.
- Participants not requiring additional therapy:
- ≥ 3 Months: 11/12 (92%)
- ≥ 4 Months: 10/12 (83%)
- ≥ 6 Months: 8/12 (67%)
- > 6 Months: 6/12 (50%)
Biologic Effect in the 6-Month Extension Study in Cohorts 3 & 4 (n=12)
- CLS-AX showed signs of biologic effect with stable mean best corrected visual acuity (BCVA) and stable mean central subfield thickness (CST) to the 6-month timepoint.
- On Optical Coherence Tomography (OCT) images, anatomical signs of TKI biologic effect were observed in anti-VEGF treatment experienced sub-responders.
About the Planned ODYSSEY Phase 2b Clinical Trial
ODYSSEY will be a multi-center, randomized, double-masked Phase 2b clinical trial to assess a total of approximately 110 treatment-naïve participants with wet AMD. In addition to loading doses of faricimab, participants will be randomized 1:1 to receive either CLS-AX administered by suprachoroidal injection via Clearside’s SCS Microinjector®, or intravitreal faricimab dosed per approved prescribing information2. The objectives of the trial are to demonstrate comparable mean change in BCVA from baseline between treatment arms with improved durability and reduced treatment burden for the CLS-AX arm, measured at 6 and 12 months.
Trial Design
- Loading Doses: Participants in both arms will receive 4 monthly faricimab (6.0 mg) loading doses. In the CLS-AX arm, participants will also receive one dose of CLS-AX (1.0 mg) at the same visit as the third loading dose of faricimab (baseline).
- Monthly Disease Activity Assessments (DAA): DAAs begin 2 months after the last faricimab loading dose to determine need for retreatment. The retreatment criteria include decrease in BCVA, increase in CST, or new macular hemorrhage3.
- Subsequent Treatments:
- In the CLS-AX arm, participants are required to be dosed with CLS-AX at least every 6 months following the last CLS-AX dose. Participants may be dosed sooner than 6 months with CLS-AX if retreatment criteria is met during a DAA.
- In the faricimab arm, participants are required to be dosed with faricimab at least every 4 months (per label). Participants may be dosed sooner with faricimab if retreatment criteria is met during a DAA. If participants are retreated earlier than 4 months, they will continue to receive further doses of faricimab at that dosing interval for the remainder of the study (per label).
- Key inclusion criteria: Treatment naïve wet AMD participants with subfoveal choroidal neovascularization (CNV) secondary to wet AMD, and BCVA of 78–24 letters.
- Endpoints: Primary endpoint is the mean change from baseline in BCVA at 6 months (Week 24 Visit) from baseline. Key secondary endpoints include mean change in CST and treatment burden reduction as measured by total injections. All endpoints will be measured at 6 months (Week 24 Visit) and 12 months (Week 48 & 52 Visits combined) from baseline.