The Emerging Role of Oral Peptide Therapeutics in Psoriasis and Beyond

Peptide drugs are emerging as a new frontier across medicine and have recently found a space in dermatology. These therapeutic agents are composed of short chains of amino acids, typically fewer than 50, and bridge the gap between small-molecule drugs and larger protein biologics.¹ Currently, more than 60 peptide-based therapeutic treatments are FDA approved, with more than 500 still in development. One of the most well-known examples is semaglutide, owned by Novo Nordisk and marketed under the brand names Wegovy, Ozempic, and Rybelsus.²

Historically, however, peptide therapies have been limited by poor membrane permeability and limited oral bioavailability, making injection the primary route of administration.^3,4 This paradigm is now shifting with advances in oral peptide technology and the introduction of agents such as icotrokinra (Icotyde; Johnson & Johnson) into the psoriasis space. Overall, oral peptide therapy represents a rapidly evolving frontier that dermatologists cannot afford to overlook.

Peptides in Medicine

Peptide therapies may be derived from endogenous molecules, such as insulin or glucagon-like peptide-1 (GLP-1) analogs, or designed synthetically to target specific biological pathways.³ Their applications span across systems, with roles in immune modulation, anti-inflammatory signaling, and cell growth regulation.

Immunomodulatory peptides can precisely alter immune responses by mimicking endogenous signaling molecules or directly interacting with immune cells, enhancing tumor-specific immunity or restoring immune tolerance in autoimmune diseases.^5,6 Anti-inflammatory peptides exert their effects through multiple mechanisms, including regulation of inflammatory mediator release, modulation of MAPK and NF-κB signaling pathways, and reduction of oxidative stress.⁷ These peptides also interfere with cytokine signaling pathways, further contributing to their role as immunomodulators.⁸

Cell growth–regulating peptides are among the most well-established therapies, functioning by binding to specific membrane receptors to directly stimulate or inhibit cell proliferation, or by modulating endocrine or paracrine growth factor secretion.⁹ GLP-1 and GLP-2 drugs further regulate cell proliferation and apoptosis in tissues throughout the body, including the pancreas and gastrointestinal tract.¹⁰ Together, these diverse mechanisms highlight the versatility of peptide therapies in modulating immune, inflammatory, and cellular processes, underscoring their growing potential as targeted therapeutics (Table^11-15).

Limitations of Peptides

Traditional peptide therapies face several significant limitations, including poor oral bioavailability, rapid enzymatic degradation, short half-lives, and limited membrane permeability. Collectively, these challenges necessitate frequent parenteral administration, which can reduce patient adherence.¹⁶

Oral delivery is particularly challenging due to peptide denaturation in the low pH of the stomach, enzymatic degradation by gastrointestinal proteases, and limited transport across tight junctions, resulting in a bioavailability of less than 2%.¹⁶ These constraints have important clinical implications, often requiring frequent injections that may increase the risk of adverse effects.¹⁷

In addition, cost remains a substantial barrier to access, with disparities driven by factors such as insurance type, high out-of-pocket costs, and prior authorization requirements.¹⁸

Oral Peptide Technology

A major breakthrough in peptide therapeutics has been the development of oral delivery systems for agents that previously required injections. Oral peptide delivery is primarily enabled by permeation-enhancing technologies that overcome the barriers posed by enzymatic degradation and poor intestinal permeability.

One of the most clinically successful approaches uses sodium-N[8-(2-hydroxybenzoyl)amino] caprylate (SNAC), which facilitates transcellular absorption via a unique mechanism involving membrane-defect formation and local pH buffering.¹⁹ Despite these advances, oral bioavailability remains low, averaging around 1%, and it is offset by high doses and strict administration conditions.²⁰

The landmark approval of oral semaglutide (Rybelsus; Novo Nordisk) for type 2 diabetes in 2019 marked a major breakthrough, followed by oral octreotide (Mycapssa; Chiesi) for acromegaly in 2020.²¹ Success in endocrinology is now being translated into advances in dermatology.

Oral peptides may offer an advantage with improved patient adherence through convenience and noninvasive, daily pill administration, which is appealing to needle-averse patients. Additional advantages include avoidance of injection-site reactions, greater target specificity, and rapid metabolism, which allow predictable on-off effects.

However, oral peptide delivery remains challenging due to enzymatic degradation and poor absorption.¹⁶ Many agents require the strict fasting or “wake-and-take” administration protocols, which may limit adherence.

Peptides in Psoriasis

Dermatologists may also be familiar with commercially available oral peptide supplements and cosmetic peptides, including collagen peptides and bioactive peptide nutraceuticals marketed for skin, hair, and nail health. Unlike FDA-approved oral peptide therapeutics, these products are generally regulated as dietary supplements rather than medications and typically lack standardized efficacy and pharmacokinetic data.²² Most recently, icotrokinra has emerged as the first oral peptide therapy approved for dermatologic use, specifically used for moderate to severe plaque psoriasis in patients 12 years and older.²³

This oral interleukin-23 receptor antagonist peptide selectively blocks IL-23 signaling, bridging the gap between the targeted efficacy of injectable biologics and the convenience of oral administration. This represents a significant advancement in dermatology, where monoclonal antibody biologics such as dupilumab (Dupixent; Sanofi/Regeneron Pharmaceuticals) and secukinumab (Cosentyx; Novartis) have transformed the treatment of conditions such as atopic dermatitis, psoriasis, and hidradenitis suppurativa. While highly effective, these therapies require injections. Icotrokinra is administered once daily on an empty stomach, offering a potentially favorable alternative to injectable regimens.¹⁵

Implications for Dermatologists

Although peptide-based therapeutics are not new to medicine, the recent emergence of orally bioavailable peptide agents has introduced a relatively novel therapeutic class within prescription dermatology. As oral peptide drugs continue to expand into the treatment of inflammatory and immune-mediated skin diseases, dermatologists are likely to become increasingly familiar with this modality, both through prescription therapeutics and broader exposure to peptide-based products already common in dermatologic and aesthetic practice.

Practical considerations for peptide therapies in dermatology include appropriate patient selection, monitoring, and counseling to optimize patient adherence and outcomes. Clinicians should monitor for therapeutic efficacy and potential adverse effects while educating patients on administration requirements and the expected timeline for response.

For icotrokinra specifically, special consideration is warranted for patients with renal impairment. Although no dose adjustment is required, close monitoring is recommended.¹⁵ Insurance coverage and access remain significant barriers, often requiring prior authorization and contributing to delays in care. Looking ahead, expansion of the oral peptide pipeline in dermatology is expected to broaden therapeutic options, with emerging indications and the potential for combination regimens to enhance efficacy.

Conclusion

While not new to medicine, oral peptide therapy is a relatively new class of drugs in dermatology. Advancements in oral peptide molecular biology, chemistry, and delivery technologies have enabled significant progress and applications across a variety of conditions, including inflammatory skin diseases such as psoriasis. For dermatologists, staying informed is essential—not only to critically evaluate emerging data but also to responsibly integrate these innovations into daily practice.

Sarita Pattisam is a third-year osteopathic medical student at the Ohio University Heritage College of Osteopathic Medicine in Dublin, Ohio.

Shannon Trotter, DO, is a board-certified dermatologist and principal investigator at DOCS Dermatology Group in Columbus, Ohio, clinical instructor at the Ohio University Heritage College of Osteopathic Medicine, and the host of the Derm-it Trotter! Don’t Swear About Skincare podcast.

References

1. Jülke EM, Beck-Sickinger AG. Peptide therapeutics: current status and future opportunity with focus on nose-to-brain delivery. Peptides. 2025;188:171404. doi:10.1016/j.peptides.2025.171404
2. Xiao W, Jiang W, Chen Z, et al. Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines. Sig Transduct Target Ther. 2025;10(1):74. doi:10.1038/s41392-024-02107-5
3. Diao L, Meibohm B. Pharmacokinetics and pharmacokinetic-pharmacodynamic correlations of therapeutic peptides. Clin Pharmacokinet. 2013;52(10):855-868. doi:10.1007/s40262-013-0079-0
4. Liu M, Svirskis D, Proft T, et al. Progress in peptide and protein therapeutics: challenges and strategies. Acta Pharm Sin B. 2025;15(12):6342-6381. doi:10.1016/j.apsb.2025.10.026
5. Karati D, Meur S, Das S, Adak A, Mukherjee S. Peptide-based drugs in immunotherapy: current advances and future prospects. Med Oncol. 2025;42(5):177. doi:10.1007/s12032-025-02739-9
6. Cai J, Li X, Du H, Jiang C, Xu S, Cao Y. Immunomodulatory significance of natural peptides in mammalians: promising agents for medical application. Immunobiology. 2020;225(3):151936. doi:10.1016/j.imbio.2020.151936
7. Liu H, Zhang L, Yu J, Shao S. Advances in the application and mechanism of bioactive peptides in the treatment of inflammation. Front Immunol. 2024;15:1413179. doi:10.3389/fimmu.2024.1413179
8. Dadar M, Shahali Y, Chakraborty S, et al. Antiinflammatory peptides: current knowledge and promising prospects. Inflamm Res. 2019;68(2):125-145. doi:10.1007/s00011-018-1208-x
9. Prevost G, Mormont C, Gunning M, Thomas F. Therapeutic use and perspectives of synthetic peptides in oncology. Acta Oncol. 1993;32(2):209-215. doi:10.3109/02841869309083914
10. Brubaker PL, Drucker DJ. Minireview: glucagon-like peptides regulate cell proliferation and apoptosis in the pancreas, gut, and central nervous system. Endocrinology. 2004;145(6):2653-2659. doi:10.1210/en.2004-0015
11. Ozempic- oral semaglutide tablet; Rybelsus- oral semaglutide tablet. DailyMed. Updated January 30, 2026. Accessed May 13, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=27f15fac-7d98-4114-a2ec92494a91da98
12. Mycapssa- octreotide capsule, delayed release. DailyMed. Updated July 24, 2025. Accessed May 13, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=58d80bc6-bdfb-4908-93e7-aace447c8d1a
13. Linzess- linaclotide capsule, gelatin coated. DailyMed. Updated November 4, 2025. Accessed May 13, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=09beda19-56d6-4a56-afdc-9a77b70b2ef3
14. Desmoda- desmopressin acetate oral solution. DailyMed. Updated March 2, 2026. Accessed May 13, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4c0e1356-d14f-cfb4-e063-6294a90acd27
15. Icotyde- icotrokinra tablet, film coated. DailyMed. Updated March 17, 2026. Accessed May 13, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aee3c963-edc0-4252-8769-cdf6c7cdc21a
16. Tyagi P, Pechenov S, Anand Subramony J. Oral peptide delivery: translational challenges due to physiological effects. J Control Release. 2018;287:167-176. doi:10.1016/j.jconrel.2018.08.032
17. Yamamoto A, Ukai H, Morishita M, Katsumi H. Approaches to improve intestinal and transmucosal absorption of peptide and protein drugs. Pharmacol Ther. 2020;211:107537. doi:10.1016/j.pharmthera.2020.107537
18. Mozaffarian D, Agarwal M, Aggarwal M, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and the Obesity Society. Am J Clin Nutr. 2025;122(1):344-367. doi:10.1016/j.ajcnut.2025.04.023
19. Colston KJ, Faivre KT, Schneebeli ST. Permeation enhancer-induced membrane defects assist the oral absorption of peptide drugs. Nat Commun. 2025;16(1):9512. doi:10.1038/s41467-025-64891-0
20. Maher S, Brayden DJ. Formulation strategies to improve the efficacy of intestinal permeation enhancers. Adv Drug Deliv Rev. 2021;177:113925. doi:10.1016/j.addr.2021.113925
21. Brayden DJ, Hill TA, Fairlie DP, Maher S, Mrsny RJ. Systemic delivery of peptides by the oral route: formulation and medicinal chemistry approaches. Adv Drug Deliv Rev. 2020;157:2-36. doi:10.1016/j.addr.2020.05.007
22. Myung SK, Park Y. Effects of collagen supplements on skin aging: a systematic review and meta-analysis of randomized controlled trials. Am J Med. 2025;138(9):1264-1277. doi:10.1016/j.amjmed.2025.04.034
23. Stein Gold L, Eyerich K, Merola JF, Torres J, Coates LC, Allegretti JR. Oral peptide therapeutics as an emerging treatment modality in immune-mediated inflammatory diseases: a narrative review. Adv Ther. 2025;42(7):3158-3172. doi:10.1007/s12325-025-03213-8
24. Icotrokinra results show potential to set a new standard of treatment in plaque psoriasis. News release. Johnson & Johnson. March 8, 2025. Accessed May 13, 2026. https://www.jnj.com/media-center/ press-releases/icotrokinra-results-show-potential-toset-a-new-standard-of-treatment-in-plaque-psoriasis
25. Icotrokinra results show signi cant skin clearance in patients with di cult-to-treat scalp and genital psoriasis. News release. PR Newswire. May 9, 2025. Accessed May 13, 2026. https://www.prnewswire.com/newsreleases/icotrokinra-results-show-signi cant-skinclearance-in-patients-with-di cult-to-treat-scalp-andgenital-psoriasis-302450309.html?tc=eml_cleartime
26. Icotrokinra long-term results a rm promise of targeted oral peptide with high rates of durable skin clearance and favorable safety pro le in di cult-totreat scalp and genital psoriasis.News release. Johnson & Johnson. October 24, 2025. Accessed May 13, 2026. https://www.jnj.com/media-center/press-releases/ icotrokinra-long-term-results-a rm-promise-oftargeted-oral-peptide-with-high-rates-of-durable-skinclearance-and-favorable-safety-pro le-in-di cult-totreat-scalp-and-genital-psoriasis
27. Johnson & Johnson seeks rst icotrokinra US FDA approval aiming to revolutionize treatment paradigm for adults and adolescents with plaque psoriasis. News release. Johnson & Johnson. July 21, 2025. Accessed May 13, 2026. https://www.jnj.com/media-center/press-releases/johnson-johnson-seeks-rst-icotrokinra-u-s-fdaapproval-aiming-to-revolutionize-treatment-paradigmfor-adults-and-adolescents-with-plaque-psoriasis
28. Johnson & Johnson seeks rst European Medicines Agency approval for icotrokinra aiming to transform the plaque psoriasis treatment paradigm. News release. Johnson & Johnson. September 11, 2025. Accessed May 13, 2026. https://www.globenewswire. com/news-release/2025/09/11/3148479/0/en/Johnson-Johnson-seeks-rst-European-Medicines-Agency-approval-for-icotrokinra-aiming-to-transform-theplaque-psoriasis-treatment-paradigm.html
29. Icotrokinra shows superiority to deucravacitinib in rst reported head-to-head trials reinforcing promise of novel targeted oral peptide for treatment of plaque psoriasis. News release. Johnson & Johnson. September 17, 2025. Accessed May 13, 2026. https://www.jnj.com/media-center/press-releases/icotrokinra-showssuperiority-to-deucravacitinib-in-rst-reported-headto-head-trials-reinforcing-promise-of-novel-targetedoral-peptide-for-treatment-of-plaque-psoriasis
30. Armstrong A, Hashim M, Feghelm L, Yang YW, Disher T. Comparative analysis of icotrokinra and approved advanced treatments for achievement of completely clear skin in patients with moderate-to-severe psoriasis: a systematic literature review and network meta-analysis. Presented at: 2026 Maui Derm Hawaii Conference; January 25-29, 2026; Maui, HI.
31. FDA approval of Icotyde (icotrokinra) ushers in new era for rst-line systemic treatment of plaque psoriasis with a targeted oral peptide. News release. Johnson & Johnson. March 18, 2026. Accessed May 13, 2026. https://www.jnj.com/media-center/press-releases/fda-approval-of-icotyde-icotrokinra-ushers-in-new-era-for-first-line-systemic-treatment-of-plaque-psoriasis-with-a-targeted-oral-peptide