On March 4, Novartis published a clinical trial of a Phase III study of Cosentyx in the treatment of moderate to severe plaque psoriasis at the 2019 Annual Meeting of the American Academy of Dermatology (AAD2019). The reason for this study is that 441 of the 543 patients with moderate to severe plaque psoriasis enrolled were Chinese. This is the first appearance of Cosentyx’s Phase III study of Chinese patients.
The study (NCT03066609) was a randomized, double-blind, placebo-controlled, international multicenter study with a 52-week evaluation of Cosentyx treatment of moderate to severe chronic plaque-type silver shavings with or without psoriatic arthritis. The efficacy and safety of patients. 441 Chinese patients were randomized into 3 groups and given Cosentyx 300 mg (n=221), Cosentyx 150 mg (n=110), and placebo (n=110) by subcutaneous injection. The primary end point of the study was the proportion of patients with PASI 75 (75% improvement in psoriasis area severity) at week 12 and the proportion of patients with IGA2011 0/1 (researcher’s overall assessment of improvement score 0/1). The secondary end point was the proportion of patients with PASI 90 at 12 weeks (the psoriasis area severity index improved by more than 90%, lesions were cleared or almost cleared).
The results show that Cosentyx has a rapid onset and excellent efficacy in Chinese patients. The improvement of the condition can be manifested in the third week of treatment, and the effect is more pronounced as the treatment time is prolonged. For example, in patients treated with Cosentyx 300 mg, 97.7% of patients achieved PASI 75 at week 16, and nearly 90% achieved PASI 90. In terms of safety, Cosentyx was well tolerated and the incidence of adverse events was consistent with previous studies.
Cosentyx appears to be particularly effective in Chinese psoriasis patients when compared to previously published placebo-controlled clinical studies. For example, the New England Journal of Medicine published two Phase III studies of Cosentyx in patients with plaque psoriasis in July 2014. Data from the ERASURE study (n=738) showed that the Cosentyx 300mg group was treated for the 12th week. The PASI 75 ratio was 81.6%; the FIXTURE study (n=1306) data showed that the proportion of PASI 75 at the 12th week of the Costentyx 300mg group was 77.1%.
Professor Zhang Jianzhong, former chairman of the Chinese Society of Dermatology and Sexually Transmitted Diseases, is the main investigator of this international multicenter trial of Chinese patients. He was also very surprised by the excellent efficacy of Cosentyx in Chinese patients with psoriasis: “The data from this clinical trial in China is very gratifying, even better than some international data in terms of efficacy and safety, or will be given to China’s silver. The treatment of psoriasis has revolutionized. Cosentyx not only contributes to the overall improvement of treatment goals, it is expected to increase the target of psoriasis treatment from PASI 75 to PASI 90 or even PASI 100. It also shows good safety. Biologics are only considered for use after phototherapy and systemic therapy are ineffective, but in the future this sequence is likely to be rewritten, and biologics may become the first line of systemic treatment, which will allow more patients with moderate to severe psoriasis to get better early. Good and safer treatment.”
The reason why Cosentyx has such excellent results is related to its unique mechanism of action. The occurrence and progression of psoriasis is the result of a combination of inflammatory cytokines and multiple signaling pathways, such as IL-6, IL-15, IL-17, IL-23, IL-27, TNF-α, INF – γ and so on. As can be seen from the figure below, IL-17A is a signaling protein downstream of the IL-23 pathway and a key factor in disease progression. Therefore, IL-17A inhibitors act more accurately and act more rapidly than IL-23 inhibitors. At the same time, IL-17A inhibitors have a very low risk of tuberculosis recurrence compared to traditional TNF-α inhibitors.
The unique mechanism of action, excellent clinical data, large patient population, and unmet clinical needs have supported the successful transformation of IL-17A monoclonal antibodies from science to business. Cosentyx, the world’s first listed IL-17A monoclonal antibody, was first approved in 2015/1/21, and its global sales revenue has approached $3 billion in just four years.
Cosentyx is currently approved by the FDA for three indications for psoriasis, arthritic psoriasis and ankylosing spondylitis, and has been approved for marketing in more than 80 countries and regions including the United States and the European Union. In November 2018, CDE released the “First Batch of Clinically Needed New Drugs List” to speed up the approval of clinically needed special effects drugs. Cosentyx is also among them. It is expected to be approved for listing in China soon. A large number of psoriasis patients in China.