银屑病新药TYK2变构抑制剂氘可来昔替尼(颂狄多)国内获批上市

Bristol-Myers Squibb China announced on October 20, 2023 that their tyrosine kinase 2 (TYK2) allosteric inhibitor tablet (trade name: Sondido) has been approved by the China National Medical Products Administration (NMPA) for the treatment of adult patients with moderate to severe plaque psoriasis who are suitable for systemic treatment or phototherapy.

Deuterated colexitinib (Sondido) is the world's first approved allosteric inhibitor of TYK2. It can be taken orally once daily, providing a new oral targeted treatment option for Chinese psoriasis patients. This news will bring new treatment options and hope to Chinese psoriasis patients.

About deuterated colexitinib (Sondido)

The allosteric inhibitor deuterated colexitinib developed by Bristol-Myers Squibb Company uses differential structural design to bind to the pseudokinase domain JH2 of TYK2, causing TYK2 to assume an inactive conformation. On September 9, 2022, the US FDA approved the marketing of deuterated colexitinib for the treatment of adults with moderate to severe plaque psoriasis who are suitable for systemic treatment or phototherapy.

The role of deuterated colexitinib (Sondido)

Deuterated colexitinib is a highly selective oral TYK2 inhibitor and has no inhibitory effect on JAK1/2/3 at therapeutic doses. Deuterated colexitinib allosterically binds to the pseudokinase domain Janus homolog 2 (JJH2) of TYK2 and selectively inhibits TYK2. Because it does not bind to the competitive ATP-binding site of the conserved domain like other JAK inhibitors, deuterated colexitinib is much more selective for TYK2 than other JAKs. This binding mechanism stabilizes the inhibitory interaction between the regulatory and catalytic domains of the enzyme, resulting in allosteric inhibition of receptor-mediated activation of TYK2 and the activation of its downstream STATs.

Through this mechanism of action, deuterated coxitinib blocks the downstream signals of IL-12, IL-23 and type I interferon, thereby producing a therapeutic effect.

Efficacy of deuterated colexitinib (Sundido)

POETYK PSO-1 (NCT03624127)[1] is a 52-week double-blind clinical phase III trial. At week 16, the deuterated colexitinib group achieved an improvement of more than 75% in the Psoriasis Area and Severity Index score (PASI 75) and static physician global assessment score of 0 or 1, that is, the proportion of static physician global assessment skin symptoms completely cleared/almost completely cleared (sPGA 0/1) was significantly higher than the placebo group or apremilast group, the number of patients reaching PASI 75 in the three groups were 58.4% vs. vs.32.1%; P < 0.0001.

In PSO-1, among subjects who received colexitinib and achieved sPGA 0/1 at Week 24, the sPGA 0/1 response rate at Week 52 was 78%. Among subjects who received colexitinib and achieved PASI 75 at Week 24, the PASI 75 response at Week 52 was 82%. Among subjects who received neocolexitinib and achieved PASI 90 at Week 24, the PASI 90 response rate at Week 52 was 74%.

Based on current data, deuterated coxitinib has been approved by the US FDA and Japanese PMDA for the treatment of plaque psoriasis.

The price of Deuterated Colexitinib (Sundido)

In the United States, the price of Deuterated Colexitinib is US$2,800 per month, and the annual medication cost is about US$34,000. The domestic price is currently uncertain, but more people still choose to use the overseas version of Deuterated Colexitinib. It is understood that Bangladesh Ziska Pharmaceutical Factory The specification of Deucrava colexitinib is 6mg*30s, and the reference price is about $550.

Summary

Deuterated colexitinib is a new small molecule TYK2 inhibitor drug currently approved by the FDA for the treatment of psoriasis. It has been launched in China on October 20, 2023. Compared with JAK1/2/3, TYK2 has higher selectivity, reducing the chance of off-target effects, and the reported safety profile is consistent with its mechanism of action. The results of two clinical phase II trials and multiple clinical phase II trials have shown that deuterated colexitinib has a significant therapeutic effect in the treatment of adult patients with moderate to severe plaque psoriasis, and the long-term expansion trial (POETYKPSO-LT The two-year results of E) confirm that deuterated colexitinib is well tolerated and safe for the treatment of moderate to severe plaque psoriasis and can become a new treatment option for patients with psoriasis. Oral administration is a very meaningful measure to improve clinical treatment.

References

[1] Yu Yanping, Chen Cheng, Fan Zhaoze, et al. New selective TYK2 inhibitor Deucravacitinib for the treatment of psoriasis [J/OL]. Chinese Dermatology and Venereology Journal, 1-11[2023-12-25]https://doi.org/10.13735/j.cjdv.1001-7089.202211112.

Recommended hot articles: