CLS-1001 – Macular Edema Associated with Non-infectious Uveitis
Uveitis is a set of conditions characterized by inflammation in the eye. Macular edema is the most dominant cause of vision distortion and loss in uveitis. We are developing a treatment for macular edema due to noninfectious uveitis using a suprachoroidal injection of CLS-TA, (“suprachoroidal CLS-TA”) our proprietary, preservative-free formulation of the corticosteroid triamcinolone acetonide (CLS-TA). We have completed an open label phase 1/2 and masked, randomized phase 2 trial, where we met our primary endpoint showing significant reduction in macular edema (p=0.002) and improvement in best corrected visual acuity (p=0.0004), each at 2 months from baseline.
We are actively enrolling patients in a 6-month controlled, randomized, masked, multi-center phase 3 clinical trial and expect to report data in early 2018. Based on our end-of-Phase 2 review with the FDA in May 2015, we expect this trial to be the only pivotal clinical trial necessary to support a 505(b)(2) NDA filing for CLS-TA.
We believe that CLS-TA will be at least as effective in treating uveitis, including the associated macular edema, as commonly used local treatments with injected corticosteroids. However, we believe that there will be improved bioavailability of drug in the retina and choroid, which may result in faster onset of therapeutic effect, an efficacy profile with similar or lower drug amounts required, and longer duration of therapeutic effect, potentially resulting in a reduced frequency of necessary injections. Based on preclinical studies of ocular distribution of TA sparing the anterior portions of the eye, including the lens, we also believe that CLS-TA may result in fewer side effects compared to commonly used local corticosteroid treatments.
CLS-1003 – Macular Edema Associated with Retinal Vein Occlusion (RVO)
RVO is a sight-threatening disorder resulting from the blockage of a retinal vein. In our RVO program, we are developing a potential treatment where suprachoroidal CLS-TA is used along with intravitreal Eylea (aflibercept).
In April 2016, we completed a 46-patient Phase 2 clinical trial with suprachoroidal CLS-TA concomitantly with intravitreal aflibercept in patients with macular edema associated with RVO. The study met the primary endpoint with significantly fewer additional intravitreal aflibercept injections in the combination arm compared to the control monotherapy intravitreal aflibercept arm (p=0.013). Visual acuity and macular edema improvements were also better in the combination arm compared to the monotherapy arm; based on these encouraging positive results, and with feedback from a recent (4Q16) end of phase 2 review with the FDA, we have commenced a Phase 3 clinical trial, the SAPPHIRE study, in RVO patients. SAPPHIRE will enroll approximately 460 patients randomized 1-1 to a combination arm (suprachoroidal CLS-TA with intravitreal aflibercept) and a control arm (monotherapy intravitreal aflibercept) with a primary best corrected visual acuity outcome at 8 weeks.
We believe that CLS-TA used along with an anti-VEGF agent may provide a differentiated therapeutic benefit for RVO patients since our combination treatment potentially couples the advantages of visual acuity gain and macular edema reduction along with a quarterly, rather than monthly, dosing schedule, compared to currently used monthly intravitreal anti-VEGF injections alone.
CLS-1004 – Diabetic Macular Edema (DME)
We have expanded our CLS-TA development programs to include focusing on treatment for another retinal vascular condition, known as diabetic macular edema, or DME. DME is a common ocular complication of diabetes and is the primary cause of vision loss associated with diabetes.
In November 2016, we began enrolling patients with DME in an open-label Phase 1/2 clinical trial to collect safety data, in addition to efficacy observations, associated with administering a combination of intravitreal Eylea and suprachoroidal CLS-TA, or following the administration of suprachoroidal CLS-TA alone, in patients with DME over a 6-month evaluation period. We expect to enroll approximately 20 patients in this trial and to report preliminary results in the second half of 2017.
We are planning a controlled, randomized, masked phase 2 trial where we will compare safety and efficacy outcomes from a combination of suprachoroidal CLS-TA and intravitreal aflibercept to intravitreal aflibercept monotherapy over a nine-month evaluation period.