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4-year data demonstrate safety, efficacy of Ilumya in plaque psoriasis

Jeffrey Crowley

The safety and efficacy of Ilumya were maintained after 4 years of treatment among patients with plaque psoriasis enrolled in the open-label reSURFACE1 trial, according to data presented at the European Academy of Dermatology and Venereology Congress.

“Here we have over 144 weeks of data, that’s after 52 weeks of an initial trial, so in total we have 4 years of long-term data,” study author Jeffrey Crowley, MD, of Bakersfield Dermatology in California, told Healio Dermatology. “Patients held a response at high levels, whether it was PASI 100, 90 or 75, patients maintained that efficacy. There wasn’t any breakthrough of disease between dosing, which can be seen with some other agents.”

Long-term safety, efficacy

The analysis included 506 patients who remained on treatment with either Ilumya (tildrakizumab-asmn, Sun Pharma) 100 mg or 200 mg during the open-label extension of the reSURFACE1 trial. Efficacy endpoints included the proportion of patients who achieved Psoriasis Area and Severity Index (PASI) 75, PASI 90 and PASI 100 at each visit in the extension study; and percentage of patients with Physician Global Assessment (PGA) response — “clear” or “minimal” with an at least grade two reduction from baseline, according to Crowley and colleagues.

Of those in the 100 mg group (n = 239), at 64 weeks, 87% achieved PASI 75, 54% achieved PASI 90 and 31% achieved PASI 100. In this dose group, results were similar at 208 weeks: 82% achieved PASI 75, 56% achieved PASI 90 and 28% achieved PASI 100.

Among those in the 200 mg group (n = 267), at 64 weeks, 82% achieved PASI 75, 52% achieved PASI 90 and 27% achieved PASI 100. Results at 208 weeks were almost identical: 82% achieved PASI 75, 55% achieved PASI 90 and 27% achieved PASI 100.

PGA responses were also favorable among patients in the 100 mg group (65% at 64 weeks and 58% at 208 weeks) and 200 mg group (63% at 64 weeks and 60% at week 208).

Twenty-two percent of patients enrolled in the extension study (n = 525) discontinued: 8% due to patient withdrawal, 5% due to singular adverse events and 4% due to loss to follow-up. Crowley and colleagues reported no significant difference in adverse events between tildrakizumab dose groups, and the occurrence of prespecified events was relatively low at less than 1.4 per 100 person-years.

“The safety profile here is quite clean,” Crowley said. “The mechanism of action here with interleukin-23 is different from what we’ve used with anti-TNF and anti-IL-17 agents, with those drugs you need to maintain high serum levels of the drug to maintain effect. When you start losing serum levels that’s associated with a loss of effect, you need more frequent dosing for those mechanisms to maintain patients. Here, you have a drug that is dosed every 3 months, where you don’t need those high serum drug levels.”

Background on reSURFACE1

The three-part, randomized, double-blind, placebo-controlled trial included patients aged 18 years or older with chronic, moderate to severe plaque psoriasis. In part one, patients were randomly assigned to 100 mg or 200 mg of subcutaneous tildrakizumab or placebo at weeks 0 and 4. During part two, patients assigned placebo in part one were randomly assigned to the study drug at 100 mg or 200 mg at weeks 12 and 16 and every 12 weeks thereafter. Patients assigned tildrakizumab in part one continued their dose of the study drug at week 16 and every 12 weeks. In part three, patients assigned to the study drug in part one were re-randomly assigned according to treatment response as measured by PASI scores:

• partial responders on 200 mg: continue current dose;
• partial responders on 100 mg: randomly assigned to 100 mg or 200 mg tildrakizumab;
• responders on either dose: continue initial dose or placebo; and
• responders assigned placebo: retreated with initial dose of study drug at relapse, at 4 weeks and every 12 weeks.

Partial response was defined as 50% to 74% improvement in PASI response, and response was defined as 75% or greater improvement in PASI response.

The extension study began at the end of the 64-week base study and included patients with a 50% or greater improvement in PASI score. During the extension, every 12 weeks, patients received the same tildrakizumab dose they were on at the end of the base study.

Based on these data and results from reSURFACE2, tildrakizumab received FDA approval for the treatment of moderate to severe plaque psoriasis in adults in spring 2018.

Additionally, data from a post hoc analysis of the reSURFACE trials published in Journal of the American Academy of Dermatology this fall demonstrated that metabolic syndrome does not affect the efficacy, safety or drug survival of tildrakizumab.

Sun Pharmaceuticals is currently conducting phase 2 studies of tildrakizumab for psoriatic arthritis, phase 3 studies of tildrakizumab for the treatment of nail and scalp psoriasis, and a real-world quality of life study in patients with moderate to severe plaque psoriasis.

“The IL-23 genetic pathway is included in many different autoimmune disease areas. We are committed to advancing science in other disease states where the IL-23 pathway may play a role, and we will continue to lead exploratory research and clinical development of Ilumya in conditions beyond plaque psoriasis,” a Sun Pharmaceuticals spokesperson said. – by Stacey L. Adams and Abigail Sutton

Reference:

Crowley J, et al. Efficacy and safety of long-term tildrakizumab for plaque psoriasis: 4-year results from reSURFACE1. Presented at: 28th European Academy of Dermatology and Venereology Congress; Oct. 9-13, 2019; Madrid.

Disclosures: Crowley reports he has received research and grant support from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Janssen, MC2 Therapeutics, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceuticals, UCB and Verrica Pharmaceuticals; has served as consultant for AbbVie, Amgen, Celgene, Dermira, Eli Lilly, Novartis, Sun Pharmaceutical Industries and UCB. He also has served on speakers bureau for AbbVie, Janssen, Eli Lilly, Novartis, Regeneron, Sanofi and UCB. Please see the poster for all other authors’ relevant financial disclosures.