Bristol Myers Squibb Announces China Approval of Sotyktu® (Deucravacitinib), the World’s First Oral TYK2 Allosteric Inhibitor for Moderate-to-Severe Plaque Psoriasis

"Refined Ease" Pursues Purity, "Silver" Brings New Life Breakthrough "Mouth"

ShanghaiOctober 20, 2023PR Newswire -- Bristol-Myers Squibb China announced the world's first tyrosine kinase 2 (TYK2) allosteric inhibitor, Sondiduo.^®(Deucravacitinib Tablets) have been approved by the National Medical Products Administration (NMPA) for adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.SondidoIt is currently the world's only approved TYK2 allosteric inhibitor, which selectively targets TYK2 through a unique "allosteric inhibition" mechanism, thereby inhibiting the signaling of key cytokines involved in the pathogenesis of psoriasis, such as interleukin (IL)-23, IL-12, and type I interferon (IFN). While precisely targeting to exert therapeutic effects, it also offers good safety. With once-daily oral administration, it provides convenient dosing and will bring a new oral targeted treatment option for psoriasis patients in China.

Over Half of Chinese Psoriasis Patients Have Moderate to Severe Conditions, Bearing Heavy Disease Burden

Psoriasis is a common chronic, systemic, inflammatory, immune-mediated disease that seriously impairs patients' physical and mental health and quality of life.^[1]In China, the prevalence of psoriasis is approximately 0.47%.^[2], the number of patients exceeds 6.5 million, nearly 60% of whom have progressed to moderate or severe conditions.^[3]In terms of disease type, plaque psoriasis is the most common type, accounting for about 80%-90% of psoriasis cases.^[4], characterized by well-defined round or oval plaques, covered with silvery white scales on the surface, which can cause skin dryness, itching, pain and other discomforts.

Although the most prominent manifestation of psoriasis is skin lesions, it is not merely a skin disorder but rather a systemic disease that affects the entire body, especially causing significant harm to patients with moderate to severe conditions. On one hand, many patients with moderate to severe psoriasis may develop various other comorbidities, including psoriatic arthritis, cardiovascular diseases, metabolic syndrome, obesity, diabetes, and inflammatory bowel disease.^[5],[6],[7]On the one hand, it further aggravates the disease burden; on the other hand, the appearance damage caused by psoriasis may also lead to patients developing inferiority complex, seriously affecting their social life.^[4], and these injuries may linger with the patient for life due to the recurring nature of the disease. The physiological and psychological burden brought by the illness is extremely heavy.

Systemic treatment has entered the "precision" era, with "diversity" and "personalization" needs urgently awaiting fulfillment.

Currently, psoriasis cannot be completely cured. Patients with moderate to severe psoriasis should promptly receive systemic treatment to improve their condition and control disease progression. In the past, traditional oral immunosuppressants were primarily used in clinical practice. However, due to the non-selective suppression of the immune system by such therapies, balancing benefits and risks has always been a major challenge. In recent years, targeted therapies represented by biologics have started to be widely used in clinical settings, advancing systemic treatment for psoriasis in China into the "precision" era. This provides patients with more effective treatment options that offer both high efficacy and good safety. However, current targeted treatment options are mainly concentrated in the field of large-molecule drugs (biologics), which can only be administered via injection, have high storage requirements, and raise concerns in clinical practice about reduced efficacy due to the immunogenicity of large-molecule drugs. As a result, the treatment needs of many patients remain unmet.

In response to this,POETYK PSO-3 IIIPrincipal Investigator of the Phase Study Project, Professor Zhang Jianzhong from the Department of Dermatology, Peking University People's Hospital"Psoriasis is a chronic, inflammatory disease with significant individual variability in clinical manifestations and severity. Doctors hope to have as many high-quality treatment options as possible to meet patients' diverse treatment needs, and oral therapy is a very important component. Previously, there were few breakthroughs in oral medications in China. The approval of deucravacitinib marks a major milestone in the systemic treatment of psoriasis, breaking through the bottlenecks of current oral therapies in terms of efficacy, safety, and convenience, expanding the scope of targeted therapies, and allowing more patients to choose a treatment plan that suits them better."

First FocusTYK2Target, a new breakthrough in the core pathogenic pathway

TYK2 is a kinase responsible for mediating the signaling of cytokines such as IL-23, IL-12, and type I IFN, which can promote the downstream production of inflammatory factors like IL-17. It is a key signaling molecule in the IL-23/Th17 axis, a well-recognized core pathogenic pathway leading to the onset and progression of psoriasis. As the world’s first approved TYK2 allosteric inhibitor,SondidoThrough a unique "allosteric inhibition" mechanism, it binds to the TYK2 regulatory domain (rather than the ATP binding site) to inhibit its activation, thereby blocking cell signaling and immune responses mediated by it. At therapeutic doses, it does not inhibit JAK1, JAK2, or JAK3.^[8], precisely targets to exert therapeutic effects while ensuring good safety.

This approval is mainly based on the results of the POETYK PSO-3 study, which confirmedSondidoSignificant Benefits and Good Safety in the Treatment of Patients with Moderate to Severe Plaque Psoriasis^[9]. A total of 220 Asian adult patients with moderate to severe plaque psoriasis were enrolled in the study, of which 81.8% were Chinese patients. The results showed that, among all randomly assignedSondidoIn the treatment group, 68.8% of patients achieved PASI 75 (at least 75% improvement in Psoriasis Area and Severity Index) by week 16, and 38.2% achieved PASI 90 (at least 90% improvement in Psoriasis Area and Severity Index, meaning almost clear or completely clear skin lesions), both significantly better than the control group (8.1% and 1.4%, respectively, P<0.0001 for both). Notably, 62.9% of patients with moderate to severe scalp psoriasis who continued treatment for 16 weeks...SondidoAchieving ss-PGA 0/1 (clear or almost clear scalp lesions) after treatment, significantly better than the placebo group (9.8%, P<0.0001), demonstrated the substantial benefit of this therapy for treating the challenging area of the scalp.

In terms of safety, in the POETYK PSO-3 studySondidoThe overall safety and tolerability were good, with adverse events mainly being mild or moderate. The most common adverse events (>10%) were upper respiratory tract infections and nasopharyngitis, consistent with the safety profile observed in the global pivotal Phase III POETYK PSO-1 and POETYK PSO-2 studies.

Ms. Chen Siyuan, Vice President of Bristol-Myers Squibb, General Manager of China and Asian Regional Markets, and President of Bristol-Myers Squibb China"We are deeply proud to bring this world's first oral TYK2 allosteric inhibitor to millions of Chinese psoriasis patients. Behind this 'first' is not only Bristol-Myers Squibb's strong innovative leadership but also our deep understanding of patient experiences and needs — by providing this highly effective and convenient oral treatment option, we give patients more time and enable them to enjoy a higher quality of life. The next step is that we will work with all parties to improve the accessibility of this innovative therapy within the multi-level medical security system, benefiting an even broader population of Chinese psoriasis patients and fulfilling our long-term commitment under the 'China 2030 Strategy'."

This material is not for promotional use. For more professional medical information, please consult a healthcare professional.

About Sondido^®(Deucravacitinib Tablets) 

Sondido(Deucravacitinib Tablets) are an oral, selective tyrosine kinase 2 (TYK2) allosteric inhibitor with a unique mechanism of action, and also the world's only approved TYK2 allosteric inhibitor.SondidoBy selectively targeting TYK2 to inhibit the signaling of IL-23, IL-12, and IFN, these cytokines are key factors involved in the pathogenesis of various immune-mediated diseases.SondidoBy binding to the regulatory domain of TYK2, high selectivity is achieved, leading to allosteric inhibition of TYK2 and its downstream functions. Within the physiological concentration range,SondidoSelectively inhibits TYK2; and at therapeutic doses,SondidoDoes not inhibit JAK1, JAK2, or JAK3.

Currently, the evaluationSondidoMultiple clinical trials for the treatment of various immune-mediated diseases are being conducted worldwide, including psoriasis, psoriatic arthritis, systemic lupus erythematosus, etc.

Note: The indications for psoriatic arthritis and systemic lupus erythematosus of Sondito have not been approved in China.

AboutPOETYK PSO-3^[5]

POETYK PSO-3 is a multi-center, randomized, double-blind, placebo-controlled Phase III clinical study designed to evaluateSondido(Deucravacitinib Tablets) (6 mg, oral, once daily) versus placebo in the efficacy and safety for Asian patients with moderate to severe plaque psoriasis. The study randomized a total of 220 Asian patients (from mainland China, Taiwan, China, and South Korea) with moderate to severe plaque psoriasis, of which 180 were from the Chinese population. Patients were randomly assigned to receiveSondidoOr placebo treatment until Week 16, after which all patients continued to receiveSondidoTreatment continued up to Week 52. The co-primary endpoints of the study were the proportions of patients achieving sPGA 0/1 and PASI 75 responses at Week 16 compared with placebo.

After completing the 52-week POETYK PSO-3 clinical study, eligible patients can participate in the POETYK PSO-LTE trial to continue receiving treatment in an open-label format.Sondido(6mg, oral, once daily) treatment.

About Psoriasis 

Psoriasis is a common chronic, systemic immune-mediated disease that seriously damages patients' physical health, quality of life, and work efficiency. At least 100 million people worldwide are affected by various types of psoriasis.^[10]Nearly a quarter of patients with psoriasis have moderate to severe conditions.^[2]In China, the prevalence of psoriasis is approximately 0.47%.^[1], the number of patients exceeds 6.5 million.

Despite the availability of effective systemic treatments, many patients with moderate-to-severe psoriasis remain under-treated or untreated, and a significant proportion of patients feel that current treatment options do not meet their needs.^[3,4]Psoriasis affects patients' emotional health, brings social pressure in daily life and workplace, and causes a decline in quality of life. In addition, psoriasis is also associated with multiple comorbidities that may impact patients' health, including psoriatic arthritis, cardiovascular disease, metabolic syndrome, obesity, diabetes, inflammatory bowel disease, and depression.

[1] Michalek, I. M., Loring, B. & John, S. M. Global report on psoriasis. (2016). Geneva, Switzerland: World Health Organization.

[2] Huang Dan, Chen Kun. Progress in Epidemiological Investigations Related to Psoriasis [J]. Theory and Practice of Diagnostics, 2021, 20(01): 48-52.

[3] Chen, K., Wang, G., Jin, H., Xu, J., Zhu, X., Zheng, M., & Gu, H. (2017). Clinic characteristics of psoriasis in China: a nationwide survey in over 12000 patients. Oncotarget, 8(28), 46381–46389.

[4] Zhang Xuejun, Chinese Psoriasis Diagnosis and Treatment Guidelines (2018 Complete Edition), Chin J Dermatol, October 2019, Vol. 52, No. 10: 667-710

[5] Bristol Myers Squibb. An Investigational Study of Experimental Medication BMS-986165 in Participants with Moderate to Severe Crohn's Disease. https://clinicaltrials.gov/ct2/show/NCT03599622. NLM identifier: NCT03599622.

[6] Dubertret L et al. European patient perspectives on the impact of psoriasis: the EUROPSO patient membership survey. Br J Dermatol. 2006 Oct;155(4):729-36.

[7] Neimann A et al. Prevalence of cardiovascular risk factors in patients with psoriasis. J Am Acad Dermatol. 2006;55(5), 829–835. https://doi.org/10.1016/j.jaad.2006.08.040.

[8] Chimalakonda, A., et al., Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors. Dermatol Ther (Heidelb), 2021

[9] Zhang, JZ et al. Deucravacitinib, an Oral, Selective Tyrosine Kinase 2 Inhibitor, in Asian Patients With Moderate to Severe Plaque Psoriasis: Findings From the Phase 3 POETYK PSO-3 Trial. Abstract N. 3448, EDAV 31st Congress 2022.

[10] World Health Organization. Global report on psoriasis. 2016. https://apps.who.int/iris/bitstream/handle/10665/204417/9789241565189_eng.pdf.psoriasis?sequence=1