PracticalDermatology

New Positive 52-Week Data for Skyrizi

AbbVie’s risankizumab (Skyrizi) met both primary and all ranked secondary endpoints, including superiority at week 52, versus secukinumab (Cosentyx, Novartis) in a head-to-head Phase 3 study. Skyrizi showed significantly higher rates of skin clearance, meeting the primary endpoint of superiority with at least a 90 percent improvement from baseline in the Psoriasis Area and Severity Index (PASI 90) at week 52. Of patients treated with Skyrizi, 87 percent achieved PASI 90 compared to 57 percent of Cosentyx treated patients at 52 weeks. At week 16, Skyrizi also met the other primary endpoint of non-inferiority to Cosentyx with 74 percent of Skyrizi patients achieving PASI 90 compared to 66 percent of Cosentyx patients.

“In this study, Skyrizi showed superior efficacy compared to Cosentyx in helping patients achieve and maintain high levels of skin clearance at week 52,” says Michael Severino, MD, vice chairman and president, AbbVie. “Head-to-head data like these are crucial to help patients and their doctors make informed treatment decisions. We are pleased to add these results to the growing body of evidence supporting Skyrizi as a differentiated treatment option for adults living with psoriasis.”

Skyrizi also showed superiority compared to Cosentyx for all ranked secondary endpoints, including PASI 100, and PASI 75, as well as a static Physician Global Assessment score of clear or almost clear (sPGA 0/1) at week 52.

Current safety data available demonstrated that the safety profile of Skyrizi was consistent with that observed in previously reported studies, with no new safety signals observed through week 52. The rates of adverse events (AEs) were comparable between Skyrizi and Cosentyx. The most common AEs were nasopharyngitis, upper respiratory tract infection, headache, arthralgia and diarrhea. The rate of serious AEs were 5.5 percent in the Skyrizi group and 3.7 percent in the Cosentyx group. Adverse events leading to discontinuation of the study drug were 1.2 percent in the Skyrizi group and 4.9 percent in the Cosentyx group. There were no deaths in either treatment group.

Skyrizi is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally.

EC Approves Stelara for Pediatric Psoriasis

The European Commission (EC) has approved the expanded use of Janssen Pharmaceutical Companies’ ustekinumab (Stelara) for the treatment of pediatric patients (ages six to 11) with moderate to severe plaque psoriasis. Ustekinumab was previously approved for use in adolescent and adult patients with plaque psoriasis, aged 12 years and older, and is now the first available biologic treatment in Europe in this patient population to selectively address the IL23/IL12 pathway, an important therapeutic target for the condition.

In one-third of 14 million cases in Europe, psoriasis begins in childhood. The condition can have a profound, long-term impact on the psychological health and overall quality of life for children. The development of pediatric psoriasis is also associated with high incidence of low self-esteem, and it can have long-term ramifications into adulthood and beyond.

“This latest EC approval is a significant milestone for young children struggling to cope with the symptoms of psoriasis,” says Lloyd Miller, Vice President, Immunodermatology Disease Area Leader, Janssen Research and Development, LLC. “We’re delighted that this therapy, which has a well-established safety and efficacy profile in adults with plaque psoriasis and other immune diseases, is now expanded to children as young as six who are living with this chronic disease.”

The EC approval is based on results from the Phase 3 CADMUS Jr study, building on the prior Phase 3 CADMUS study, which found ustekinumab improved the signs and symptoms of plaque psoriasis, as well as healthrelated quality of life (HrQOL), in paediatric patients aged six to 11 years old. The primary endpoint was the proportion of patients who achieved a physician’s global assessment (PGA) score of Cleared (0) or Minimal (1) at week 12. Secondary endpoints included the proportion of patients achieving improvements in psoriasis area and severity index of ≥75 percent (PASI 75), ≥90 percent (PASI 90), and change from baseline in Children’s Dermatology Life Quality Index (CDLQI) at week 12.

In the study, 44 patients (aged six to 11 years) from nine countries were enrolled and treated with at least one injection of ustekinumab. At baseline, the mean duration of psoriasis was 3.5 (standard deviation 2.49) years. At week 12, subjects treated with ustekinumab showed clinically meaningful improvements in their psoriasis and HrQOL. At week 12, 77.3 percent achieved PGA 0/1, 84.1 percent achieved PASI 75, and 63.6 percent achieved PASI 90. The mean change from baseline in CDLQI was -6.3. All patients were followed for up to 52 weeks after the first administration of ustekinumab. Improvements in PGA 0/1, PASI 75, PASI 90 and CDLQI were maintained through to week 52 (75.6, 87.7, 70.7, and 58.3 percent, respectively).

Safety data from CADMUS Jr were consistent with the known safety profiles reflected in respective current prescribing information labels and ustekinumab was generally welltolerated by pediatric patients with plaque psoriasis. Overall, 34 patients had more than one adverse event (AE; [77.3 percent]) and three had more than one serious AE (6.8 percent). One patient had a serious infection (mononucleosis), 29 had infections (65.9 percent), and 12 had infections requiring treatment (27.3 percent). In general, the AEs and other safety data reported up to one year in two pediatric patient studies (CADMUS and CADMUS Jr) were similar to those seen in previous studies in adults with plaque psoriasis.

This marketing authorization follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), issued on December 12, 2019.

Analysis: Anti-IL-17 Biologics Demonstrate Greater Cumulative Benefits for Psoriasis

In a recent meta-analysis comparison of cumulative clinical benefits of biologics for the treatment of psoriasis over 16 weeks ixekizumab and brodalumab were shown to have greater cumulative clinical benefit for patients with psoriasis, according to study findings. The study, published in the Journal of the American Academy of Dermatology, excluded recently approved biologics.

For the study, researchers conducted a systematic literature review to identify Phase 3 trial data on Psoriasis Area and Severity Index (PASI) responses for biologics during 12 and 16 weeks of treatment. They compared cumulative clinical benefit, measured by area-under-the-curve for PASI 75, PASI 90, and PASI 100 using the network meta-analysis (NMA) and Bayesian methodology on the relative probability of achieving percent of maximum AUC.

The results showed that among biologics approved for psoriasis treatment, anti-IL-17 biologics demonstrated consistently greater cumulative clinical benefits on PASI 75, PASI 90, and PASI 100 over the 12- or 16-week period than anti-IL-23 and other biologics. For biologics with 12-week data, ixekizumab and brodalumab showed greater cumulative benefits for PASI 75, PASI 90, and PASI 100 than secukinumab, followed by guselkumab, infliximab, adalimumab, ustekinumab, and etanercept. Ixekizumab showed greater cumulative benefits than all other biologics reporting 16-week data.

National Psoriasis Foundation Establishes New Funding Opportunities

The National Psoriasis Foundation (NPF) has established two new funding opportunities for 2020 focused on advancing research related to prevention and milestones toward a cure for psoriatic disease.

Inspired by the National Institute of Health Accelerating Medicines Partnership (AMP), NPF will invest an estimated $6.5 million over five years to establish the Psoriasis Prevention Initiative (PPI). Aiming to identify an intervention that will prevent the onset of psoriatic disease, disease relapse or relevant comorbidities, the PPI grant focuses on multi-institution, multi-disciplinary, team-based research.

“Funding for PPI is very different from our other grants as the intention is to create an opportunity for the research and clinical communities to combine their perspectives to accelerate psoriatic disease research efforts,” says Randy Beranek, president, and CEO, NPF. “We are uniquely positioned to do this and feel that supporting a collaborative effort will improve the prospect for success in finding a prevention for psoriatic disease.”

NPF has also launched the Milestones to a Cure grant which aims to support psoriatic disease research focused on treatment durability, remission/relapse, prevention, and personalized medicine.

To learn more about all NPF grant offerings, visit psoriasis.org/grants.