Janssen Seeks to Expand Plaque Psoriasis Indication for Ustekinumab to Adolescents

Supplemental biologics license application submitted to FDA

A supplemental biologics license application has been submitted to the FDA seeking approval of ustekinumab (Stelara, Janssen Biotech, Inc.) for the treatment of adolescents (12–17 years of age) with moderate-to-severe plaque psoriasis.

It is estimated that 7.5 million Americans have psoriasis, which can range from mild to severe and disabling, and approximately one-third of those affected develop the immune-mediated disease before 20 years of age. Ustekinumab, a human monoclonal antibody that targets interleukin (IL)-12 and IL-23 cytokines, has been approved in the U.S. for the treatment of adults with moderate-to-severe plaque psoriasis since September 2009.

The application is supported by data from the phase 3 CADMUS registration study, which evaluated the efficacy and safety of ustekinumab in the treatment of adolescents (12–17 years of age) with moderate-to-severe plaque psoriasis. Results from the CADMUS study were published in the Journal of the American Academy of Dermatology in May 2015. The efficacy and safety profile of ustekinumab in the CADMUS trial was consistent with the profile of this anti-IL-12/23 monoclonal antibody as previously observed in adults receiving ustekinumab.

CADMUS, a phase 3, randomized, double-blind, placebo-controlled, parallel, multicenter trial, evaluated the efficacy and safety of ustekinumab in pediatric patients 12–17 years of age with moderate-to-severe plaque psoriasis. Patients (N = 110) had been diagnosed with psoriasis more than six months prior to first study agent administration and had a Psoriasis Area Severity Index (PASI) score greater than or equal to 12, a Physician's Global Assessment (PGA) score greater than or equal to 3, and body surface area (BSA) involvement of at least 10%. In addition, patients were inadequately controlled with topical therapy or were candidates for systemic/phototherapy.

Patients were randomized 1:1:1 to receive subcutaneous injections of placebo, ustekinumab standard dosing (SD) (intended to achieve exposures comparable to adults), or ustekinumab half standard dosing (HSD) (intended to achieve exposures half of those seen in adults). Ustekinumab dosing tiers were determined by body weight. Patients receiving placebo crossed over to receive ustekinumab SD or HSD at weeks 12 and 16; all patients continued with maintenance dosing every 12 weeks through week 40.

Final efficacy and safety evaluations were made at weeks 52 and 60, respectively. The primary endpoint of the study was a PGA score of cleared (0) or minimal (1) at week 12. Secondary endpoints at week 12 included at least a 75% or 90% improvement in psoriatic skin lesions, as measured by PASI 75 or PASI 90, and improvement in quality of life, as measured by the Children's Dermatology Life Quality Index (CDLQI), a patient-reported outcome.

Another phase 3 study, CADMUS Jr., is ongoing to evaluate the efficacy and safety of ustekinumab in the treatment of younger pediatric patients 6 to 11 years of age living with moderate-to-severe plaque psoriasis.

Source: PR Newswire; December 16, 2016.