Takeda Drugs $4B deal succeeds in two key plaque psoriasis trials
For plaque psoriasis drugs to be successful in clinical trials, they don't need to clear up all the redness and other signs of the inflammatory skin disease. But complete skin clearing is a benchmark many patients and doctors seek, and an experimental drug from Takeda Pharmaceuticals now has data from two pivotal studies showing it can achieve that goal.
Takeda said Thursday that the once-daily drug zaxoxetinib helped more than half of the patients in the study achieve clear or nearly clear skin at 16 weeks. Armed with these results, the Tokyo-based drugmaker plans to submit applications to the FDA and other regulatory agencies around the world next year.
Zasocitinib (formerly TAK-279) is a small molecule inhibitor of TYK2, an enzyme that plays a role in signaling pathways associated with immune diseases such as plaque psoriasis. In 2022, Bristol-Myers Squibb's Sotyktu became the first drug in the TYK2 inhibitor drug class to receive FDA approval. This oral small molecule is approved for the treatment of moderate to severe plaque psoriasis in adults. This target holds promise as a treatment for a range of immune diseases, sparking research and business development interest across the biopharmaceutical industry. Months after Sotyktu was approved, Takeda struck a deal to acquire zasocitinib from Nimbus Therapeutics for $4 billion upfront.
In an interview earlier this year, Takeda President of Research and Development Andy Plump said the differences between zasocitinib and Bristol's Sotyktu were reflected in the drug's Phase 2b data. He said the activity of Bristol's once-daily drug tapers off throughout the day. In contrast, zasocitinib's selectivity for TYK2 enables higher doses to achieve target inhibition throughout the day.
“We achieved close to 100% inhibition within 24 hours, which is probably at least three to four times higher than what you see with Sotyktu and their next doses,” Plump said. “That's the difference. It's a truly first-in-class TYK2 inhibitor.”
The data reported Thursday came from two Phase 3 clinical trials that enrolled a total of 1,801 patients. Each study compared the Takeda drug to a placebo and Otezla, an Amgen drug that is the standard treatment for plaque psoriasis. Takeda did not release specific data but said zaxoxitinib met its two primary goals for evaluating its drug based on two skin clearance measures at week 16. Responses were observed as early as week 4 and continued to increase through week 24. Additionally, Takeda said the studies met other secondary endpoints and showed the potential to achieve complete skin clearance.
Takeda said zaxoxitinib was generally well tolerated. The most common adverse events reported at week 24 were upper respiratory tract infection, nasopharyngitis, and acne. No new safety signals were discovered. Takeda plans to publish more detailed results at an upcoming medical meeting. The company added that it plans to submit regulatory reports to the FDA and other regulators in fiscal 2026, which begins April 1.
Additional studies of zasocitinib are ongoing. One of them is testing the drug head-on with Sotyktu. BMS has broader plans for Sotyktu; the drug is under FDA review for psoriatic arthritis, and Phase 2 testing in lupus and Sjogren's syndrome is underway. But Sotyktu has underperformed in inflammatory bowel disease (IBD), an area where Takeda believes the drug can excel.
When the BMS drug failed phase 2 testing in ulcerative colitis in 2021, the company remained hopeful that higher doses would lead to better results. Plump said it remains to be seen whether TYK2 inhibition can treat IBD, but Takeda is able to offer higher doses of zaxoxitinib that can achieve greater inhibition of the TYK2 target than other drugs in the class.
“Not only do we have best-in-class research in psoriasis, but we think we have an opportunity to make a breakthrough in IBD,” Plump said.
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