Psoriasis Pipeline Update: Will An Oral IL-23 Inhibitor Be the Next Psoriasis Blockbuster?

Dr. Amy Paller discusses the latest data on JNJ-2113 with DermWire.

Investigational JNJ-2113 is a novel oral interleukin (IL)-23R antagonist peptide that binds with high affinity to the IL-23R. It is the first and only targeted oral peptide designed to block the IL-23 receptor, which underpins the inflammatory response in psoriasis and other IL-23-mediated diseases.

New Phase IIb data presented at the European Academy of Dermatology and Venereology (EADV) Congress 2023 in Berlin showed that the JNJ-2113 induces a strong systemic pharmacodynamic response in people living with moderate to severe plaque psoriasis when compared with placebo.

If this research pans out, JNJ-2113 could be a game changer in psoriasis, says Amy Paller, MD. She is the chair of the department of dermatology, director of the Skin Biology and Diseases Resource-Based Center, and the Walter J. Hamlin Professor of Dermatology Professor of Dermatology and Pediatrics (Dermatology) at Northwestern University’s Feinberg School of Medicine in Chicago.

FRONTIER 1 evaluated three once-daily dosages and two twice-daily dosages of the agent taken orally by patients with moderate-to-severe plaque psoriasis. Results indicated the proportion of patients who achieved Psoriasis Area and Severity Index (PASI) 75 was 9.3% for the placebo group, and 37.2%, 58.1%, 51.2%, 65.1%, and 78.6% for the JNJ-2113 groups at week 16, respectively. Similarly, the proportion of patients who achieved PASI 90 was 2.3% for the placebo group, and 25.6%, 51.2%, 26.8%, 46.5%, and 59.5% for the treatment groups at week 16, respectively, the study showed.

“JNJ-2113 was statistically significant at every endpoint,” Dr. Paller tells DermWire. “It was a huge success, and the medication itself is oral and yet is targeted toward IL-23, which is where we think the action is in psoriasis,” she says.

So far, this drug seems to produce a biologic level of activity in an oral medication.

“If an oral drug can truly achieve what a biologic can achieve, we have real winners,” she says. Moreover, there were no adverse events beyond what was seen among patients who received a placebo in the study.

There are other oral disease-modifying drugs to treat psoriasis such as methotrexate (MTX) and cyclosporine, but they are not ideal.  “MTX requires lab tests and can take months before it kicks in, “she says.  Deucravacitinib is a first-in-class, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor.  "This is kind of in the JAK inhibitor family, “ she says. “It has not been shown to have adverse effects and is looking safe but still may have some of the  baggage  associated with the JAK family.”

An effective oral treatment for psoriasis will be an especially important addition for children.

“I am really excited to get this in front of pediatricians,’ she says. No kid wants an injection, and no parent really wants to put their child through rounds of injections. “It

a real struggle within the family.”