A new oral medication for plaque psoriasis, which targets the same inflammation pathway as currently available injectable therapies, has shown promising results in a phase 2 dose-finding study for the treatment of moderate to severe disease.
In the study, 255 patients with plaque psoriasis were randomly assigned to receive either a placebo or an oral Interleukin (IL)-23 receptor antagonist peptide called JNJ-77242113 (Janssen). Of those who received the oral medication at the highest dose of 100 mg twice daily, 79% showed a reduction in the Psoriasis Area and Severity Index (PASI) by at least 75% (PASI 75) compared to 9% of patients who received the placebo, reported Dr. Robert Bissonnette of Innovaderm Research in Montreal, Quebec, Canada, and colleagues.
„The extent of psoriasis reduction observed at higher doses of JNJ-77242113 at week 16 was comparable in magnitude to the responses seen with several of the injectable biologics currently approved for psoriasis,“ the researchers wrote in The New England Journal of Medicine (NEJM).
The researchers found that 60% of patients who received the 100 mg dose of the medication showed a PASI-90 response, which is a positive outcome compared to Phase 3 studies of two other oral therapies for psoriasis, Deucravacitinib (Sotyktu) and Apremilast (Otezla). However, they cautioned against drawing further conclusions from these data as these agents were not directly tested against JNJ-77242113 in comparative studies.
The investigational product is an oral IL-23 receptor antagonist peptide that selectively blocks the proximal signaling of IL-23 and the production of downstream inflammatory cytokines such as IL-17, the authors explained.
„The modulation of the interleukin-23 pathway using monoclonal antibodies has proven effective in treating psoriasis and is associated with a favorable safety profile compared to older oral therapies (e.g., Cyclosporin, Acitretin, Methotrexate, and Dimethyl fumarate),“ the investigators wrote.
Currently available biologic agents targeting IL-23 include Guselkumab (Tremfya), Risankizumab (Skyrizi), and Tildrakizumab (Ilumya). These agents require intravenous or subcutaneous administration, while JNJ-77242113 is taken orally, theoretically giving it an advantage in terms of patient preference.
The new medication must be taken twice daily on an empty stomach, at least two hours before eating or drinking. Patients are instructed to wait an additional 30 minutes before eating or drinking after taking the medication.
The results of the study have convinced at least one former skeptic of the drug’s effectiveness. Dr. Mark G. Lebwohl, Dean for Clinical Therapeutics at the Icahn School of Medicine at Mount Sinai in New York, NY, initially doubted that a peptide targeting a receptor could be effective. However, he now believes that it is „profoundly effective.“
Dr. Lebwohl has become an investigator for the currently recruiting Phase 3 study ICONIC-LEAD, which is testing JNJ-77242113 against a placebo in adolescents and adults with moderate to severe plaque psoriasis.
In a companion editorial to the study in NEJM, Dr. Joel M. Gelfand, Vice Chair of Clinical Research and Medical Director of the Dermatology Clinical Studies Unit at the University of Pennsylvania in Philadelphia, noted that if the PASI 90 rate is confirmed in larger studies, it would be similar to the most effective injectable biologics, with no evidence of increased side effects at higher doses.
However, he warned that larger studies will be needed to determine whether severe adverse events such as COVID-19, an infected cyst, and a suicide attempt reported during the study were coincidental or related to the inhibition of interleukin 23 signaling.
During the study, there were no reports of deaths, serious adverse cardiovascular events, or cancer.
The study was supported by Janssen Research and Development. Bissonnette disclosed institutional research funds from Janssen as well as participation on advisory boards and honoraria. Gelfand disclosed consulting for Janssen Biotech. Lebwohl disclosed institutional research funds from Janssen, but no personal honoraria.
Medscape award-winning medical journalist Neil Osterweil has been writing regularly for Medscape for many years.