Oral Peptide Therapeutics as an Emerging Treatment Modality in Immune-Mediated Inflammatory Diseases: A Narrative Review

Immune-mediated inflammatory diseases (IMIDs), such as psoriasis, psoriatic arthritis, and inflammatory bowel disease, encompass a heterogenous group of conditions associated with chronic inflammation. Systemic treatments for patients with IMIDs include parenterally delivered monoclonal antibodies (mAbs) that disrupt specific cytokine and cytokine receptor binding interactions, and orally delivered small molecules that inhibit certain enzymes involved in the regulation of inflammatory signaling. Many patients prefer oral alternatives to injectables, but currently available oral advanced therapies are less effective than mAbs and/or have tolerability concerns. Thus, an unmet need exists for additional oral treatment options for patients with IMIDs. Therapeutic peptides can be designed to possess characteristics that provide both the target selectivity typically associated with parenterally delivered mAbs and an oral route of administration. Oral peptide therapeutics are an area of intense research in several therapeutic areas, and, although some oral peptides are available for certain indications, such as diabetes, there are currently no targeted oral peptides available for the treatment of patients with IMIDs. Icotrokinra (JNJ-77242113), which is currently in development to treat patients with various IMIDs, is the first targeted oral peptide designed to selectively inhibit interleukin (IL)-23 signaling by blocking the IL-23 receptor on human immune cells. In a phase 2b study in adults with moderate-to-severe psoriasis, icotrokinra showed a significant dose-response effect versus placebo, and a tolerable safety profile at Week 16. Sustained skin clearance and no safety signals were observed through Week 52 in the extension study to the phase 2b study. Ongoing phase 2 and phase 3 clinical studies in patients with psoriasis, psoriatic arthritis, and ulcerative colitis will provide data to inform the therapeutic potential of icotrokinra to address the unmet need in these diseases.