Ophthotech Provides Update on Zimura Complement Programs for Treatment of Eye Diseases
Ophthotech announced the initiation of an open-label phase 2a clinical trial of Zimura (avacincaptad pegol), the company’s complement factor C5 inhibitor, in patients with wet age-related macular degeneration (AMD). Zimura will be administered in combination with Lucentis (ranibizumab), an anti-vascular endothelial growth factor (anti-VEGF), in patients with wet AMD who have not been previously treated with anti-VEGF drugs. A range of Zimura dosing regimens will be assessed. Clinical trial sites have been identified and activated.
“We believe that supplementing anti-VEGF therapy with a complement inhibitor such as Zimura may have the potential to further enhance the efficacy of anti-VEGF monotherapy in wet AMD,” Kourous A. Rezaei, MD, Senior Vice President of Medical Strategy, said in a company news release. “Our earlier phase 1/2a clinical trial assessing Zimura in combination with Lucentis, while small and uncontrolled, showed intriguing results. A recent peer-reviewed publication from the Journal of Clinical Investigation from Scripps Research Institute provided further support that anti-VEGF therapy upregulates complement activation and therefore that complement inhibition during anti-VEGF therapy may have therapeutic merit. These findings establish a foundation to pursue further development of Zimura in wet AMD.”
“We are excited to move the company forward with opportunities consistent with our overall strategy to develop Zimura for both orphan diseases and larger indications in the back of the eye, such as age-related retinal diseases,” Glenn P. Sblendorio, Chief Executive Officer and President of Ophthotech, said in the news release.
The company also announced that it remains on track to initiate two additional Zimura clinical trials before the end of the year. The company’s strategy in orphan indications will be led by a randomized, controlled clinical trial to assess Zimura monotherapy in Stargardt disease, a devastating orphan retinal disease-causing vision loss during childhood or adolescence. The other trial will be an open-label phase 2a clinical trial evaluating Zimura in combination with anti-VEGF therapy for idiopathic polypoidal choroidal vasculopathy (IPCV), an age-related eye disease. Ophthotech is also planning a phase 2a clinical trial of Zimura monotherapy for intermediate/posterior noninfectious uveitis, an orphan inflammatory disease of the back of the eye. This trial is planned to initiate in 2018.
The company is in the process of modifying its dry AMD program. Following the recent announcements of competitors’ conflicting topline results from two clinical trials assessing the role of two different types of complement inhibitors, one blocking the alternative complement pathway (did not meet primary endpoint) and the other blocking all three complement pathways (met primary endpoint), in the treatment of geographic atrophy, a dry form of AMD, Ophthotech has decided to modify its ongoing phase 2/3 clinical trial of Zimura monotherapy (which blocks all three complement pathways) in geographic atrophy. Ophthotech had originally planned to enroll 300 patients in an initial stage of the ongoing trial, with an interim analysis scheduled for the 18-month time point, and to potentially enroll up to an additional 600 patients thereafter. The trial will be modified to accelerate the anticipated timeline to obtain topline data by reducing the number of patients, shortening the time point for attaining the primary efficacy endpoint and thereby reducing the cost to complete the study. The modified study design will incorporate patients already enrolled in the study.
Zimura is designed to target and inhibit the complement protein C5, a central component of the complement cascade. Inhibition of C5 in the complement cascade prevents the formation of key terminal fragments (C5a and C5b-9) regardless of which of the three complement pathways (classical, lectin or alternative) induced their generation. C5b-9 is involved in the formation of the membrane attack complex (MAC: C5b-9), which can cause cell death through disruption of the cell membrane. By inhibiting the terminal steps of complement activation at the level of C5, we believe a therapeutic benefit may be achieved.
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