Johnson & Johnson's First-in-Class Oral Peptide Drug Icotrokinra Approved by FDA for Moderate-to-Severe Plaque Psoriasis

Another powerful player has emerged in the field of oral peptide drugs.

On the evening of March 18, Johnson & Johnson announced that its oral peptide drug Icotrokinra received FDA approval for marketing, intended for treating moderate to severe plaque psoriasis (PsO) in adolescents aged 12 years and older and adults.

This is the world's first and only oral peptide drug targeting the IL-23 receptor.

The IL-23 receptor is a key mechanism in the inflammatory response of plaque psoriasis and has potential application value in other IL-23-mediated diseases. Icotrokinra can achieve single-digit pM-level binding affinity with IL-23R, offering patients a new treatment option in the form of a once-daily tablet and ushering in a new era in the field of psoriasis treatment.

In 2017, Johnson & Johnson entered into a licensing and collaboration agreement with Protagonist Therapeutics to develop a first-generation IL-23R drug. The scope of the collaboration was expanded in 2019 to include a second-generation IL-23R drug, with the total deal value reaching up to $1.025 billion. In 2021, Johnson & Johnson revised the collaboration agreement again, securing global rights to two second-generation IL-23R drugs (Icotrokinra and JNJ-5186), with the total deal value potentially reaching up to $980 million.

Due to the acidic environment in the human stomach causing changes in the structure of proteins, peptides, and other substances, as well as various enzymes in the intestines further degrading them, peptide drugs often get dismantled before they can take effect, making it extremely difficult for peptide drugs to be formulated into oral preparations that exert therapeutic effects.

The approval and market launch of Icotrokinra not only once again broke through the technical bottleneck of oral peptide drugs but also expanded the competitiveness of oral peptide drugs into the autoimmune treatment field.Notably, multiple companies had previously invested in oral peptides for metabolic fields such as diabetes treatment and weight loss, engaging in prolonged competition.

Multi-Target Battle, Relying on Technological Breakthrough

The metabolic field with GLP-1 as a key target can be considered the main battleground for the development of oral peptide drugs. After Eli Lilly's tirzepatide claimed the top spot as the "blockbuster drug," areas such as blood sugar reduction and weight loss in the metabolic field have become must-contend territories for most pharmaceutical companies both in China and internationally. Oral peptides, due to their high technical difficulty, can be either an insurmountable "gap" or a protective "barrier."

By the end of 2025, Novo Nordisk's once-daily weight loss version of the oral semaglutide tablet (25mg) received FDA approval for marketing. It is used to reduce excess body weight and maintain long-term weight loss while lowering the risk of major adverse cardiovascular events.This is also the first approved oral peptide GLP-1 drug for weight management.

The drug is administered in an oral dosage form. By adding the absorption enhancer SNAC (a derivative of sodium salicylate), it protects peptides from degradation in the gastrointestinal tract, thereby enabling oral absorption.

Currently, among the oral peptide drugs under research, most take effect in the gastrointestinal tract, and only a few can enter the bloodstream, mostly being small molecules.Semaglutide (oral tablets) is the only active peptide drug that alters the environment, enters the bloodstream, and is absorbed orally.

In February this year, Hengrui and Kailera Therapeutics jointly announced that the Phase II clinical trial (HRS9531-T-201) of once-daily oral Rempopotide tablets conducted in 166 obese adults in China had achieved positive topline data. Based on the encouraging clinical data, Hengrui Medicine will advance Rempopotide tablets into Phase III trials in China, and the partner Kailera plans to initiate a global Phase II trial in 2026.

The Nextpharma database of PharmaCube shows that Rvipotide tablets are currently the only oral GLP-1R/GIPR agonist drug to have obtained Phase II weight loss study data.In May 2024, Hengrui Medicine granted Kailera the exclusive rights to develop, manufacture, and commercialize its GLP-1 class innovative drug portfolio, including Ripotipeptide, outside of Greater China.

While pushing the world's first cAMP-biased long-acting GLP-1 receptor agonist Enotuglutide to market, Xianwei Da reached a nearly $500 million collaboration with Pfizer. This "rising star" has also developed an oral formulation.

Xianwei Da Bio applies its proprietary biased GLP-1 technology to oral formulations, developing oral Enotuglutide (code name XW004). The drug is currently in Phase II clinical trials. Data shows that the oral bioavailability of this drug is 3-5 times higher than existing oral GLP-1 therapies, a breakthrough that helps reduce dosage, minimize adverse reactions, and significantly improve treatment safety and patient compliance.

In addition to the GLP-1 receptor, targets such as the IL-23 receptor, IL-17 receptor, and PCSK9 are also areas where oral peptide drugs are attempting to make breakthroughs.

IL-23 Receptor is the Interleukin-23 receptor, which inhibits the IL-23/TH17 inflammatory pathway and is mainly used to treat autoimmune diseases such as plaque psoriasis and ulcerative colitis.

Johnson & Johnson's Icotrokinra has been approved for marketing, filling the gap for oral peptide drugs in this field. Currently, apart from Johnson & Johnson, the main company developing oral peptide drugs targeting the interleukin receptor family is Protagonist Therapeutics, the original developer of Icotrokinra.

Protagonist Therapeutics is a clinical-stage biopharmaceutical company focused on the discovery and development of "novel chemical entities based on peptides." Its goal is to leverage its proprietary platform to design and optimize "structurally constrained" peptides—combining the advantages of traditional small molecules with those of antibody/large-molecule biologics, while minimizing the limitations associated with conventional peptide (and protein) drugs.

Currently, Protagonist Therapeutics is developing PN-881 with its proprietary peptide technology platform.This is an oral IL-17 peptide antagonist currently in Phase I clinical trials, being developed for indications such as psoriasis, psoriatic arthritis, hidradenitis suppurativa, and spondyloarthritis.

In September 2025, Merck announced positive results from the Phase III CORALreef Lipids study of its oral PCSK9 inhibitor Enlicitide for the treatment of hypercholesterolemia, marking a breakthrough advancement.

Enlicitide (MK-0616) is an oral cyclic peptide PCSK9 inhibitor developed by Merck & Co., administered orally once daily. An application for its market approval has been submitted, and it is on track to become the world’s first oral PCSK9 inhibitor.

Results from the Phase III CORALreef Lipids study of Enlicitide show that the study successfully met all primary and key secondary endpoints. At week 24, compared to the placebo group, patients in the Enlicitide group achieved statistically and clinically significant reductions in LDL-C levels, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB) levels, and lipoprotein(a) levels. In terms of safety, the incidence of adverse events was comparable to placebo, with no serious hepatic, renal, or muscle toxicity; daily oral administration resulted in patient compliance as high as 97%, significantly higher than injectable formulations.

From Semaglutide to Icotrokinra and Enlixibat, oral peptide drugs are undergoing revolutionary changes. With technological breakthroughs and product launches, production related to the future commercialization of these products has become a new challenge for pharmaceutical companies, while also presenting new opportunities. An increasing number of CXO companies in China are seizing this opportunity.

CXO Industry Chain Welcomes New Growth Opportunities

In recent years, the expansion of oral peptide drugs, including GLP-1, has become a new growth engine for CXOs.

From the current layout of CXOs in China, the industry is showing a pattern led by the forefront and breaking through with differentiation——Head CXOs secure large orders with global production capacity and integrated capabilities; niche CXOs focus on their unique strengths, positioning themselves at key links; innovative CROs concentrate on original R&D to complete the ecosystem, jointly forming a system that covers the entire industry chain.

Among them, leading CXOs such as WuXi AppTec and ChemPartner have become major beneficiaries of this round of dividends. For instance, in recent years, WuXi AppTec's TIDES (peptides + oligonucleotides) has become its most sought-after business. In just the first three quarters of 2025, the year-on-year revenue growth of this business reached 121.1%, with income exceeding 7.8 billion yuan, and it is expected to surpass 10 billion yuan for the entire year without any issue.

Upon closer examination, the core driver of this business growth is the global scaling of GLP-1, which has made the synthetic production capacity of peptide drugs a scarce resource.

As early as 2011, WuXi AppTec had taken the lead in establishing capabilities in peptide research and testing, and gradually built an integrated CRDMO platform around peptide drugs. By September of last year, the total volume of its solid-phase peptide synthesis reactors had increased to over 100,000 liters, ranking among the top global peptide production capacities.

Public information shows that WuXi AppTec is the largest CDMO supplier of Eli Lilly's tirzepatide in China, and it has also undertaken multiple oral peptide project orders, occupying a key position in the global peptide supply chain.

Pharmaron recently also reached a cooperation with Eli Lilly, focusing on the commercial production of the oral GLP-1 drug Orforglipron. For this purpose, Eli Lilly will invest 200 million US dollars in Pharmaron to support its capacity construction. The choice of this GLP-1 giant to partner with Pharmaron undoubtedly values the latter's potential in small molecule CDMO.

In addition, companies such as Nuotai Biotech, Sinopharm Peptide, and Kintor Pharmaceutical have built unique barriers in areas like peptide active pharmaceutical ingredient (API) and intermediate process development, thereby entering this field.

Since 2003, NovaTech Biologics has been deeply engaged in peptide active pharmaceutical ingredients (API). Relying on an "API + formulation" integrated solution, it has achieved continuous performance growth during the peptide boom. Currently, its product pipeline includes semaglutide, liraglutide, tirzepatide, as well as oligonucleotide drugs.

The core advantage of Sinovation Biotech lies in its production capabilities covering all technical routes, including solid-phase synthesis, liquid-phase synthesis, and chemical modification. Thanks to these technical capabilities, in the first three quarters of last year, the revenue and net profit of Sinovation Biotech increased significantly by 53.96% and 123.03%, respectively.

Jinkai Bio's revenue has experienced continuous rapid growth, benefiting from the scaling up of its SNAC intermediate business. Compared with injectable formulations, the oral version not only requires a larger amount of API but also needs to add the permeation enhancer SNAC to improve the drug's stability and absorption efficiency in the gastrointestinal tract.

Jinkai Biochemistry is one of the few companies globally with the capability to stably supply SNAC at the ton level. Currently, it has established the first commercial production line for SNAC in China that complies with FDA cGMP standards. Since 2021, Jinkai Biochemistry has been collaborating with Novo Nordisk as the supplier of KDA01 (SNAC), a key intermediate for oral semaglutide, and is currently the sole exclusive supplier in China.

In January 2024, when oral semaglutide was approved for marketing in China, the share price of Jinkai Biotech experienced a limit-up, which sufficiently proves that securing a key position can also allow one to share in the large market of oral peptides.

In the upstream source innovation segment of the industry, Zhongsheng Full Peptide has formed a differentiated layout, focusing on the discovery and development of novel peptide-based therapeutic drugs. Earlier this year, it successively secured peptide candidate drug development collaborations with Eli Lilly and Novartis.

It can be said that the approval and market launch of Johnson & Johnson's oral peptide drug has once again opened up vast development opportunities for related companies in China. In the future, as the application areas of oral peptides continue to expand, Chinese pharmaceutical companies and CXOs are also expected to benefit from more growth dividends in the global peptide wave.

In the field of psoriasis, this February,Novartis SecukinumabApproved for a new indication in China, used to treat moderate to severe plaque psoriasis in children. In addition, there are multiple IL-23 targeted drugs under research and already on the market, including Picoquimab (Piqochi) marketed by Innovent Biologics, Johnson & Johnson's Guselkumab, etc.

And important developers of oral peptide formulations include:AbbVie, AstraZeneca, Eli Lilly, Ferring, Ipsen, Johnson & Johnson, Merck & Co., Novartis, Novo Nordisk, Sanofi, Takeda, Teva, etc.The main markets for oral peptide formulations will be in the fields of oncology, metabolic diseases, and central nervous system disorders.

The peptide industry is currently in an unprecedented golden age of development. Compared with small-molecule chemical drugs, peptide drugs exhibit higher biological activity and specificity; compared with biologics, they stand out with advantages such as low immunogenicity, high purity, and lower production costs. Overall, peptide drugs are highly favored for their high activity, low dosage, and low toxicity.

Reference: PharmaCube

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