TYK2 inhibitor produces significant improvement in phase 2 psoriasis trial

09/12/2018

By Gene Emery

(Reuters Health) - A capsule containing an experimental drug that inhibits the tyrosine kinase 2 (TYK2) signaling pathway dramatically reduced the size and severity of plaque psoriasis lesions, in a double-blind phase-2 study funded and conducted in part by the manufacturer, Bristol-Myers Squibb.

After 12 weeks of treatment, a 75% reduction on the Psoriasis Area and Severity Index was seen in 39% of patients getting a 3 mg daily dose, 69% taking 3 mg twice daily, 67% receiving 6 mg twice daily and 75% on a dose of 12 mg daily. A similar reduction was logged in just 7% of placebo patients.

"It's a wonderful experience to see this type of response early in development and have a quiet profile in terms of adverse effects," chief author Dr. Kim Papp of Probity Medical Research in Waterloo, Ontario, told Reuters Health in a telephone interview.

"We are fortunate to now have an armamentarium of medications to target these signaling pathways and are often able to achieve complete clearance of plaque psoriasis. Nonetheless, we still have patients who do not respond or stop responding to our most advanced treatments," Dr. Tiffany Mayo, a dermatologist at University of Alabama at Birmingham, said in an email to Reuters Health.

"This new TYK2 inhibitor offers an exciting new possible treatment that demonstrates efficacy and has the advantage of being an oral agent, which is preferred by many patients," said Dr. Mayo, who was not connected with the research.

Results from the test of the drug, identified as BMS-986165, were reported Wednesday at the 27th European Academy of Dermatology and Venereology Congress in Paris and online by the New England Journal of Medicine.

A phase 3 test, known as POETYK, is currently enrolling volunteers.

The new study tracked 267 volunteers with moderate-to-severe plaque psoriasis covering at least 10% of the body. That represents about one fifth of people affected by the disease.

To be eligible, the patients also had to have a Psoriasis Area and Severity Index score of at least 12 on the 73-point scale. The average score was 18. Nearly half had previously been treated with a biologic agent. Patients who had showed little sensitivity to a TYK2 inhibitor in the past were excluded.

A dose of 3 mg every other day showed no significant effect versus placebo when it came to attaining a 75% reduction.

The chances of getting a 90% reduction on the psoriasis index were 2% with placebo, 16% with 3 mg daily, 44% with 3 mg twice daily, 44% with 6 mg twice daily and 43% with 12 mg once daily. A complete clearance of lesions was achieved in 0%, 9%, 9%, 18% and 25% of the groups, respectively.

Conditions tended to worsen when treatment stopped, but that's not necessarily bad news, said John Throup, lead developer for the drug at Bristol-Myers Squibb.

"We wanted to see if there was a rebound effect" when therapy was halted, he told Reuters Health by phone. "The nice thing about the data is, it does not appear to be the case."

The highest dropout rate due to side effects was in the 45-member group getting 6 mg twice daily. Three people (7%) discontinued treatment.

The rates of any adverse effect were in the 50%-59% range with placebo and among volunteers getting less than 3 mg twice daily. The rates were 64% with 3 mg twice daily, 80% with 6 mg twice daily and 77% with 12 mg daily.

The most common side effects in the higher-dose groups were nasopharyngitis (16% with 6 mg twice daily), diarrhea (9% with 12 mg daily) upper respiratory tract infection (9% with 6 mg twice daily) and acne (9% with 12 mg daily).

Eighty two clinical sites in eight countries were involved in the study.

Drugs such as ustekinumab, guselkumab, acitretin, methotrexate and cyclosporine are already known to be effective against psoriasis. Dr. Papp said BMS-986165 is more selective than other TYK2 inhibitors and alternatives are needed because "nothing works for everyone, and nothing works forever."

SOURCE: https://bit.ly/2x30tcg

N Engl J Med 2018

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