Hengrui Medicine's Domestic Alopecia Areata Drug Amaxitinib (SHR0302) Nears Market Approval with Over RMB 1 Billion R&D Investment

Recently, Hengrui Pharma announced that it had received a "Notice of Acceptance" from the National Medical Products Administration (NMPA). The company’s marketing authorization application for Elmacitinib Sulfate Tablets (SHR0302) has been accepted by the NMPA, with the proposed indication being severe alopecia areata in adults.

SHR0302 tablets are a highly selective JAK1 inhibitor, with 16-fold selectivity for JAK1 over JAK2. It is an orally administered small-molecule innovative drug independently developed in China, holding first-class intellectual property rights. According to the announcement, no domestically developed JAK1 inhibitors have been approved for marketing in the field of alopecia areata to date.

Janus kinases (JAKs) are a family of signaling molecules that serve as intracellular adapters for type I and type II cytokine receptors, belonging to the non-receptor tyrosine kinase class. To date, four proteins have been identified within the JAK family: JAK1, JAK2, JAK3, and tyrosine kinase 2 (TYK2).

JAK/Signal Transducer and Activator of Transcription (STAT)-mediated gene regulation is involved in various physiological responses, including hematopoiesis, immune regulation, inflammation, tissue repair, apoptosis, and adipogenesis. Therefore, JAK inhibitors, as drugs that selectively inhibit JAK kinases, can modulate the signaling pathways of inflammatory factors, thereby exerting anti-inflammatory and immunomodulatory effects for the treatment of autoimmune diseases. Among them, JAK1 is widely expressed in tissues and has broad application prospects.

SHR0302 tablets, as a highly selective JAK1 inhibitor, exert anti-inflammatory and immunosuppressive biological effects by inhibiting JAK1 signaling. In June 2024, Hengrui Pharma’s Phase III clinical trial of SHR0302 tablets for alopecia areata (CTR20213405) met the protocol-prespecified primary endpoint.

This is a randomized, double-blind, placebo-controlled Phase III study evaluating the efficacy and safety of SHR0302 tablets in adult patients with alopecia areata. Led by Professor Zhang Jianzhong from Peking University People’s Hospital as the principal investigator, the study enrolled a total of 330 adult patients with severe alopecia areata. Both the 8 mg and 4 mg dose groups of SHR0302 tablets demonstrated significant superiority over the placebo group in achieving the primary endpoint. Long-term treatment with SHR0302 showed favorable safety and efficacy profiles in adult patients with severe alopecia areata, with no new safety signals identified compared to other JAK1 inhibitors.

In addition to the indication for alopecia areata, three additional indications for SHR0302 tablets have had their marketing authorization applications accepted by the National Medical Products Administration.

In August 2023, Hengrui Pharma submitted a New Drug Application (NDA) (CXHS2300071) for this product for the treatment of adult patients with active ankylosing spondylitis who have had an inadequate response to or are intolerant of nonsteroidal anti-inflammatory drug (NSAID) therapy. On November 4, 2023, the second NDA for this product was accepted by the Center for Drug Evaluation (CDE) (CXHS2300097), indicated for adult and adolescent patients aged 12 years and older with moderate-to-severe atopic dermatitis who have had an inadequate response to topical therapies or other systemic treatments, or who are intolerant to such therapies. On November 30, 2023, the third NDA for this product was accepted by the CDE (CXHS2300108), indicated for adult patients with moderate-to-severe active rheumatoid arthritis.

Furthermore, SHR0302 tablets are currently undergoing clinical studies in multiple indications, including ulcerative colitis and psoriatic arthritis, with the majority having entered Phase III clinical trials. In 2018, Hengrui Pharma licensed JSHR0302 to Arcutis Biotherapeutics, Inc. in the United States, thereby enabling broader application of this promising selective inhibitor.

To date, the cumulative R&D expenditure for SHR0302-related projects has amounted to approximately RMB 1.00373 billion.

Alopecia areata is an autoimmune disorder and a common form of inflammatory, non-scarring hair loss. It clinically presents as sudden-onset, well-demarcated, circular patches of hair loss on the scalp. Approximately half of patients experience recurrent episodes, which may persist for several years or even decades. In severe cases, it can lead to complete hair loss on the scalp or even over the entire body. The condition can occur at any age, is most prevalent among young and middle-aged adults, and shows no significant gender predilection.

According to incomplete statistics, alopecia areata is the second most prevalent form of hair loss worldwide, affecting approximately 147 million people globally.Among them, there are approximately 4 million patients in China, and the incidence rate among children and adolescents accounts for as high as 12.8% of the total alopecia areata patient population. A survey across six provinces in China showed that the prevalence of alopecia areata was 0.27%, with nearly 18.1% of alopecia areata patients diagnosed before the age of 18.

In the United States, mild-to-moderate alopecia areata (hair loss <50%/SALT score <50) accounts for more than half of the 800,000 patients with alopecia areata. Furthermore, according to a study published in JAMA Dermatology, the prevalence and incidence of alopecia areata among individuals aged 12–17 years in the United States increased between 2016 and 2019, peaking in early adulthood (ages 18–44).

For patients with severe alopecia areata, existing treatments include topical immunotherapy, systemic glucocorticoid therapy, and immunosuppressive therapy.

Local immunotherapy should be continued for at least 3 to 6 months before evaluating efficacy. The response rate is approximately 30%–50%, and adverse reactions are relatively common, primarily including contact dermatitis, lymphadenopathy, and hyperpigmentation. Systemic glucocorticoids, administered orally or via intramuscular injection, are associated with a high relapse rate if tapered too rapidly or discontinued abruptly, and long-term use entails numerous adverse effects. Immunosuppressants are effective only in a subset of patients; however, due to their relatively frequent adverse effects, higher costs, and high relapse rates upon discontinuation, they are not recommended as first-line agents in clinical practice.

Existing medications still fail to meet the needs of patients with severe alopecia areata,Some patients still respond poorly to existing medications or discontinue treatment due to intolerable adverse effects, underscoring an urgent need for the development of new, effective, and safe therapeutic agents. According to Market Data Forecast, the global hair loss treatment market was valued at USD 8.81 billion in 2021 and is projected to reach USD 13.44 billion (approximately RMB 89.6 billion) by 2026, representing a compound annual growth rate (CAGR) of 8.8%.

In the face of this multi-billion-dollar blue-ocean market, several oral drugs targeting the same mechanism for alopecia areata have already been approved and launched globally, including Pfizer’s ritlecitinib capsules, Eli Lilly’s baricitinib tablets, and Sun Pharmaceutical Industries’ deuruxolitinib tablets. According to data from the EvaluatePharma database, the combined global sales of ritlecitinib capsules and baricitinib tablets reached approximately $941 million in 2023.

In China, no domestically developed JAK1 inhibitor has yet been approved for marketing to treat severe alopecia areata, but numerous pharmaceutical companies have established relevant clinical pipelines. In addition to Hengrui Pharma, other domestic pharmaceutical companies such as Zeltis Pharma, Kelun Pharmaceutical, and Qiyuan Biologics have also laid out candidate therapies for alopecia areata, with some products already in Phase II and Phase III clinical trials. As major domestic pharmaceutical companies rapidly advance the market launch of related products, it is believed that this billion-level blue ocean market for alopecia areata will witness new changes.

References:
1. Hengrui Pharma, “Marketing Application for Ivarmacitinib Sulfate Tablets, a Domestically Produced JAK1 Inhibitor, for the Indication of Alopecia Areata Accepted”

2. Insight Database, “Hengrui’s JAK1 Inhibitor ‘Ivarmacitinib’ Files for Marketing Approval in China for a New Indication: Treatment of Alopecia Areata”