Sun Pharma has announced that two pivotal Phase-3 clinical trials evaluating the efficacy and safety of the investigational IL-23p19 inhibitor antibody tildrakizumab (MK-3222) in patients with moderate-to-severe plaque psoriasis met their primary endpoints for both evaluated doses.
The co-primary efficacy endpoints of the placebo controlled studies (MK-3222-010 and MK-3222-011) were: the proportion of participants with Psoriasis Area Sensitivity Index 75 (PASI 75) response at week 12 compared to placebo and the proportion of participants with a Physician's Global Assessment (PGA) score of clear or minimal with at least a 2 grade reduction from baseline at week 12 compared to placebo. The overall safety profile of tildrakizumab in both Phase-3 clinical trials was consistent with the safety data observed in previously reported studies.
The second study (MK-3222-011) also included an etanercept comparator arm, with a key secondary endpoint comparing tildrakizumab and etanercept on PASI 75 and PGA. Tildrakizumab 200mg was superior to etanercept on both PASI 75 and PGA endpoints at week 12, while the 100 mg dose showed superiority to etanercept on PASI 75 only.
"Tildrakizumab is the first IL-23p19 inhibitor to demonstrate positive results in Phase-3 clinical trials for the treatment of moderate-to-severe plaque psoriasis, further validating the importance of the role of IL-23 in psoriasis. We are encouraged by these results and the potential to provide a new treatment option to patients with moderate-to-severe plaque psoriasis, a disease that often takes both a physical and emotional toll on their lives," stated Dilip Shanghvi, Managing Director, Sun Pharma. "We would like to thank the over 1,800 patients who participated as well as the investigators at more than 200 clinical sites."
"While there are existing treatment options for psoriasis, many patients continue to struggle with the debilitating impact this chronic disease can have on their bodies, their lives and their families," said Kim Papp, MD, clinical trial investigator and president, Probity Medical Research, Inc. "Tildrakizumab works by selectively targeting IL-23, specifically the p19 component of the cytokine. Blocking this key cytokine helps control the pathogenic cells responsible for the inflammatory process of psoriasis. These new data are encouraging and support the potential of tildrakizumab as a new treatment option for patients."
The preparations for submission of a Biologics License Application to the U.S. Food and Drug Administration are proceeding. The detailed findings from the Phase-3 clinical trials will be presented at upcoming scientific meetings.
Tildrakizumab Study Design
Tildrakizumab Phase-3 studies are randomized, placebo-controlled, multicenter studies designed to demonstrate efficacy of tildrakizumab in moderate-to-severe plaque psoriasis compared to placebo and comparative drug and to assess safety and tolerability. Psoriasis Area Severity Index (PASI) and Physician Global Assessment (PGA) were the primary endpoints in the studies. A PASI score is a measure of psoriatic plaque redness, scaling and thickness and extent of the involvement in each region of the body. Treatment efficacy is often measured by reduction of PASI from baseline (i.e. 75 percent reduction is known PASI 75,) a 90 percent reduction is known as PASI 90 and PASI 100 is total clearance of skin disease. PGA measures lesion thickness, erythema and scaling across all of a patient's psoriasis lesions in order to determine the disease activity on a six-point scale from "clear" to "severe."
Tildrakizumab is an investigational humanized, anti-IL-23p19 monoclonal antibody designed to selectively block the cytokine IL-23. Evidence from human genetics studies suggest that inhibition of IL-23 may provide an approach for the treatment of some inflammatory conditions.