As Clearside CEO Daniel H. White noted during a conference call announcing the trial results, Clearside is unique in that it has exclusive rights to deliver drugs into the suprachoroidal space using its proprietary microinjector. Clearside believes the advantages of suprachoroidal delivery are the ability to target higher concentrations of drugs, fewer typical steroid side effects such as elevated IOP and cataract, and applicability to a wide range of eye diseases.
Of the 160 patients enrolled in the phase 3 PEACHTREE trial, 96 were randomized to the treatment arm to receive two 4.0-mg doses of suprachoroidal CLS-TA 12 weeks apart, and 64 were randomized to undergo sham procedures at the same 12-week interval. Patients were evaluated every 4 weeks for a total of 24 weeks, and a total of 155 patients, or 97% of those enrolled, completed the full evaluation period of the trial. In the PEACHTREE trial, 47% of patients who received suprachoroidal CLS-TA every 12 weeks gained at least 15 letters in BCVA, as measured using the ETDRS scale, from baseline to week 24, compared to 16% of patients who underwent a sham procedure. This improvement, which was the primary endpoint of the trial, was statistically significant (P<.001). Moreover, in terms of improvements in BCVA, the mean change from baseline was better in the treatment arm than the sham arm at each monthly evaluation. The mean improvement from baseline was maintained throughout the evaluation period, with 9.6 letters gained at week 4 and 13.7 letters at week 24 in the active arm, compared to 1.2 letters at week 4 and 2.9 letters at week 24 in the control arm, respectively.
In a key secondary endpoint, administration of suprachoroidal CLS-TA resulted in a mean reduction from baseline of 157 microns in central subfield thickness at week 24 in the active arm compared to a 19 micron mean reduction in the sham arm, a result that was also statistically significant (P<.001). Subgroups of patients will be followed for 6 additional months to assess the durability of the effects from treatment.
Suprachoroidal CLS-TA was generally well tolerated, with no treatment-related serious adverse events reported in the trial. Through 24 weeks, corticosteroid-related elevated IOP adverse events were reported for approximately 11.5% of patients in the CLS-TA treatment group, compared to no patients in the sham group.
“The positive data reflect well on the suprachoroidal approach," said Rahul N. Khurana, MD, on the call held to discuss results. Dr. Khurana is an investigator for PEACHTREE, a partner at Northern California Retina Vitreous Associates, and a clinical associate professor of ophthalmology at UCSF Medical Center. “The gain of 15 letters was the greatest proportional increase I’ve ever seen in a uveitis trial and CLS-TA resulted in lower increases in IOP than I’ve ever seen in my practice. The PEACHTREE study was the first pivotal phase 3 clinical trial of a drug candidate for patients with uveitic macular edema in which a BCVA measure was the primary efficacy endpoint, potentially raising the bar for future trials in this population." Based on the positive results, and if marketing authorization is obtained from the FDA, said Dr. Khurana, suprachoroidal CLS-TA has the potential to become a new paradigm for treatment of visual impairment associated with macular edema associated with noninfectious uveitis.
“Having nearly 50% of the PEACHTREE trial patients treated with suprachoroidal CLS-TA gain 15 or more letters in vision is highly compelling," said White in a press release. "It represents a huge step forward in advancing suprachoroidal administration of CLS-TA toward becoming a powerful new approach in potentially treating blinding eye diseases. We currently expect to submit a new drug application for suprachoroidal CLS-TA in patients with macular edema associated with uveitis to the FDA in the fourth quarter of 2018.”
Clearside’s stock price (symbol CLSD) jumped approximately 60% when the shares opened for trading following the announcement of the trial results.