氘可来昔替尼:治疗中至重度斑块型银屑病的新药

Introduction: Deuterated colexitinib is an oral, selective allosteric tyrosine kinase 2 (TYK2) inhibitor developed by Bristol-Myers Squibb Company of the United States. It is the world's first oral selective allosteric tyrosine kinase 2 (TYK2) inhibitor and is used to treat adult patients with moderate to severe plaque psoriasis who are suitable for systemic therapy or phototherapy. On September 9, 2022, the FDA approved deuterated coxitinib for marketing.

The therapeutic status of deuterated colexitinib in psoriasis

It is the only TYK2 inhibitor approved by the US Food and Drug Administration (FDA). The drug is the first innovative drug for the treatment of moderate to severe psoriasis. Compared with other tyrosine-protein kinase (JAK) inhibitors, deuterated coxitinib has greater prospects for its highly selective inhibition of inflammatory pathways through allosteric inhibition.

Approval History

Deuterated colexitinib was developed by Bristol-Myers Squibb to treat a variety of immune-mediated diseases, including psoriasis, psoriatic arthritis, lupus, and inflammatory bowel disease. It was first approved in the United States on September 9, 2022, for the treatment of adult patients with moderate to severe plaque psoriasis who are suitable for systemic treatment or phototherapy. It was subsequently approved in Japan on September 26, 2022 for the treatment of plaque psoriasis, systemic pustular psoriasis and erythrodermic psoriasis.

Mechanism of action

Psoriasis is an immune-mediated chronic inflammatory skin disease induced by both genetics and environment. Tyrosine kinase 2 (TYK2) and signal transducer and activator of transcription (STAT) are major signaling pathways regulated by cytokines and are crucial in mediating inflammation and immune responses. Deuterated colexitinib is a first-in-class, highly selective oral tyrosine kinase 2 (TYK2) inhibitor that mediates the transcription of key inflammatory mediators through the TYK2/STAT pathway and is involved in the treatment of psoriasis.

Clinical efficacy

A study showed that after three consecutive years of treatment with deuterated colexitinib, the clinical response rate of Psoriasis Area and Severity Index (PASI) 75 was maintained at 73.2%. Deuterated colexitinib, the first oral TYK2 inhibitor approved for adult patients with moderate-to-severe plaque psoriasis who are eligible for treatment with systemic therapy or phototherapy, demonstrated consistent efficacy and safety.