Clinical Trials

Date: 2016-10-01

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the 25th European Academy of Dermatology and Venereology (EADV) Congress

Company: Merck&Co (USA - NJ) Sun Pharmaceuticals (India)

Product: tildrakizumab

Action mechanism:

• monoclonal antibody. Tildrakizumab is an investigational humanized, anti-IL-23p19 monoclonal antibody designed to selectively block the cytokine IL-23. In clinical studies for the treatment of chronic plaque psoriasis, tildrakizumab demonstrates efficacy in blocking inflammation by blocking IL-23. Other potential indications, which may be evaluated in future, include psoriatic arthritis and Crohn’s disease.
• The drug has been initially developed by Merck&Co. In September 204, Merck & Co and Sun Pharmaceutical Industries have concluded a licensing agreement for tildrakizumab, (MK-3222).
• In July 2016, Sun Pharma had announced a strategic licensing agreement with Almirall on the development and commercialization of tildrakizumab for psoriasis in Europe.

Disease: moderate-to-severe plaque psoriasis

Therapeutic area: Autoimmune diseases - Dermatological diseases - Inflammatory diseases

Country: Australia, Canada, Japan, UK, USA (NCT01722331) Austria, Belgium, Canada, Czech Republic, Denmark, France, Germany, Hungary, Italy, The Netherlands, Poland, USA (NCT01729754)

Trial details:

• • MK-3222-010/(reSURFACE1 is being conducted to evaluate the efficacy and safety/tolerability of subcutaneous MK-3222, followed by an optional long-term safety extension study, in participants with moderate-to-severe chronic plaque psoriasis. (NCT01722331)
• MK-3222-011/(reSURFACE2 is being conducted to evaluate the efficacy and safety/tolerability of tildrakizumab (SCH 900222/MK-3222) in a population of participants with moderate-to-severe plaque psoriasis. (NCT01729754)

Latest news:

• • On October 1, 2016, Sun Pharmaceutical Industries will announce latebreaking data from two pivotal Phase-3 clinical trials (reSURFACE 1 and 2) achieving the primary endpoint with tildrakizumab in patients with moderate-to-severe plaque psoriasis at the 25th European Academy of Dermatology and Venereology (EADV) Congress in Vienna, Austria.  The Phase-3 data results through week 28 are being presented for the first time as part of the “Late Breaking News” Session.
• Tildrakizumab clinical trials included over 1,800patients from more than 200 clinical trial sites worldwide. In the trials, an average of 63 percent of patients achieved 75 percent of skin clearance (Psoriasis Area Sensitivity Index or PASI 75) by week 12 after only two injections, and 77 percent achieved 75 percent skin clearance after 28 weeks and three injections of the 100 mg dose of tildrakizumab (64 percent and 80 percent in reSURFACE1, 61 percent and 74 percent in reSURFACE2). Similarly, an average of 57 percent and 66 percent of patients had a Physician’s Global Assessment (PGA) score of “clear” or “minimal” with the 100 mg dose at weeks 12 and 28 respectively. Those receiving the 200 mg dose also saw an average of 64 percent and 78 percent of patients achieving PASI 75 at weeks 12 and 28 respectively. Also, 59 percent and 69 percent of the patients had PGA score of “clear” or “minimal” at weeks 12 and 28 respectively.
• The data further showed that a higher number of patients on tildrakizumab achieved PASI 90 and 100 compared to placebo and etanercept. An average of 37 percent and 36 percent of patients on tildrakizumab achieved PASI 90 at week 12 with the 100 mg dose and 200 mg dose respectively which increased to 54 percent and 59 percent at week 28. Correspondingly, an average of 13 percent on tildrakizumab achieved PASI 100 at week 12 regardless of dose with an increase to 24 percent for the 100 mg dose and 30 percent for the 200 mg dose at week 28.
• The overall safety profile of tildrakizumab in both Phase-3 clinical trials was consistent with the safety data observed in previously reported studies. The incidences of severe infections, malignancies, and  extended major cardiovascular events (MACE) were low and similar across treatment groups (1-3 percent). Preparations for regulatory submissions in both the U.S. and Europe are proceeding.
• • On May 4, 2016, Sun Pharmaceutical Industries announced that two pivotal Phase-3 clinical trials evaluating the efficacy and safety of 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.

Is general: Yes