Breakthrough for Severe Alopecia Areata: Domestic Innovative Drug Restores Over 80% Hair Growth, NDA Submitted

On June 12, Zelgen announced that the pivotal Phase III clinical trial of its independently developed gacitinib hydrochloride tablets (formerly known as jakitinib hydrochloride tablets) for the treatment of severe alopecia areata had met its primary efficacy endpoint, achieving statistical significance (p<0.0001). Zelgen stated that it would accelerate the marketing approval process for gacitinib hydrochloride tablets for the indication of treating patients with severe alopecia areata.

Zelgen’s independently developed garsocitinib hydrochloride is a novel dual inhibitor of JAK and ACVR1, classified as a Class 1 new drug. Upon successful market launch, it is expected to address substantial patient demand, with sales potentially exceeding expectations.

This is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial conducted at 44 hospitals, including Peking University People’s Hospital and the Hospital for Skin Diseases of the Chinese Academy of Medical Sciences. A total of 425 patients with severe alopecia areata who met the protocol criteria were randomly assigned to receive either ritlecitinib tablets 50 mg twice daily (BID), 75 mg BID, or placebo. After an independent, unblinded third-party team analyzed the data from patients who completed 24 weeks of treatment in this trial,The results showed the primary efficacy endpoint, namely the percentage of subjects with a Severity of Alopecia Tool (SALT) score ≤20 (i.e., hair coverage >80%) at 24 weeks of treatment.Both groups of gikacitinib tablets were significantly superior to the placebo group, achieving statistical significance (p<0.0001).

In terms of safety, ruxolitinib demonstrated a favorable safety and tolerability profile in patients with severe alopecia areata. Detailed data from this clinical trial will be presented at upcoming academic conferences.

Currently, the extension study of the Phase III clinical trial of ruxolitinib for the treatment of severe alopecia areata is ongoing. Previously, the company announced the results of the Phase II clinical trial of ruxolitinib hydrochloride tablets for the treatment of severe alopecia areata, which were selected for an oral presentation at the 30th Congress of the European Academy of Dermatology and Venereology (EADV) in 2021.

The results showed that among 82 subjects with severe alopecia areata (SALT score ≥50%) who completed the 24-week efficacy evaluation, the response rates (proportion of subjects achieving a ≥50% reduction in SALT score from baseline at Week 24) in the 50 mg BID, 150 mg QD, and 200 mg QD groups were 59.2%, 63.3%, and 60.0%, respectively; the median changes in SALT scores from baseline at Week 24 were 52.25%, 58.13%, and 54.33%, respectively. When including all 111 subjects across the three groups, regardless of whether they completed the 24-week efficacy evaluation, the overall response rates were 50.0%, 48.7%, and 37.5%, respectively. All dose groups demonstrated favorable tolerability and safety profiles. According to the "Chinese Clinical Diagnosis and Treatment Guidelines for Alopecia Areata (2019)," only approximately 8% of patients with severe alopecia areata (SALT score ≥50%) recover without treatment.

Jacotinib Hydrochloride Tablets are currently undergoing multiple clinical studies for immune-inflammatory diseases and fibrotic disorders. In October 2022, the New Drug Application (NDA) submitted by Zelgen for Jacotinib Tablets in the treatment of intermediate- and high-risk myelofibrosis was accepted by the National Medical Products Administration (NMPA) and is currently under review.

Furthermore, Zelgen is conducting clinical trials of jakacitinib tablets for autoimmune diseases, including moderate-to-severe atopic dermatitis (Phase III), ankylosing spondylitis (Phase III), idiopathic pulmonary fibrosis (Phase II), and moderate-to-severe plaque psoriasis (Phase II). The Phase II/III clinical trial of jakacitinib hydrochloride tablets for the treatment of non-segmental vitiligo in adolescents aged 12 years and older and adults has been approved. The research on jakacitinib tablets for the treatment of myelofibrosis has received support from the National Major Science and Technology Special Project for “Major New Drug Development.”

Alopecia Areata (AA) is a common inflammatory, non-scarring alopecia characterized clinically by the sudden onset of well-demarcated, circular patches of hair loss on the scalp. Approximately half of patients experience recurrent episodes, with the condition persisting for years or even decades. In severe cases, it can lead to complete hair loss on the scalp or even the entire body. This condition can occur at any age, is more prevalent among young and middle-aged adults, and shows no significant gender predilection.

Research data indicate that alopecia areata is the second most prevalent form of hair loss worldwide, affecting approximately 147 million people globally, including around 4 million in China. A six-province survey in China reported a prevalence rate of 0.27%, with nearly 18.1% of patients diagnosed before the age of 18.

The pathogenesis of alopecia areata remains unclear; it is currently believed to result from an autoimmune attack on hair follicles mediated by immune cells and inflammatory cytokines. Furthermore, emotional distress and stress are recognized as triggers for alopecia areata. Following the onset of the condition, patients may develop psychiatric disorders such as recurrent depressive disorder, depression, and anxiety disorders. Anxiety and depression, in turn, can exacerbate alopecia areata, creating a vicious cycle. Due to the incompletely understood pathogenic mechanisms, current treatments yield suboptimal satisfaction rates and are associated with high recurrence rates.

As public attention to hair-related issues intensifies, the “hair loss economy” has emerged, manifested in the pharmaceutical industry by the research and development of related innovative drugs. According to Frost & Sullivan, the market size for hair loss treatment in China is projected to reach RMB 41.2 billion in 2026, with a compound annual growth rate (CAGR) of nearly 12%.

Therapeutic agents for alopecia areata hold promising market prospects. In recent years, scientists have been actively exploring effective treatments for this condition, with Janus kinase (JAK) inhibitors emerging as a class of particular interest.

However, currently only two JAK inhibitors—Eli Lilly’s baricitinib and Pfizer’s ritlecitinib—have been approved in China for the treatment of alopecia areata; prior to this, no domestically produced JAK inhibitor had been approved for marketing in China for this indication.

As an innovation-driven pharmaceutical company, Zelgen has developed a portfolio of products with differentiated competitive advantages across multiple therapeutic areas, leveraging its small-molecule drug R&D and industrialization platform as well as its novel complex recombinant protein drug R&D and industrialization platform, which includes bispecific and trispecific antibodies.

Zelgen’s successful Phase III clinical trial will fill the gap in the domestic market for JAK inhibitors targeting severe alopecia areata. Upon successful commercial launch, the drug is expected to meet substantial patient demand, with sales potentially exceeding expectations. Furthermore, other Chinese pharmaceutical companies, such as Hengrui Medicine and Kelun Pharmaceutical, have related products in development, warranting future anticipation.