Amid JAK debacle, Bristol Myers settles in for FDA's long review of potential first TYK2 drug
Bristol Myers Squibb has $4 billion hopes for its late-stage TYK2 inhibitor deucravacitinib, but the FDA’s recent negative review for the JAK inhibitor class has dampened hopes somewhat. Now, the agency will get its first good look at TYK2, and Bristol Myers will have to wait and hold its breath.
The FDA has set a target review date of Sept. 10, 2022, for deucravacitinib, a potential first-in-class oral inhibitor for the TYK2 signaling pathway in psoriasis that would be a challenger to the controversial JAK inhibitors, the drugmaker said Monday.
The agency will base its review on findings from the Phase III POETYK-PSO program, which tested deucravacitinib in a three-way head-to-head against Amgen’s Otezla and placebo in moderate-to-severe plaque psoriasis.
In terms of PASI 75, a measure of disease severity, 58.7% and 53.6% of patients on deucravacitinib achieved PASI 75 response respectively, in the POETYK-PSO-1 and POETYK-PSO-2 studies, Bristol Myers said in April. Meanwhile, just 12.7% and 9.4% of placebo patients and 35.1% and 40.2% of patients on Otezla achieved the same.
Even more promising for Bristol Myers, deucravacitinib maintained its edge over Otezla between 24 and 52 weeks of treatment. At the six-month check-in, 69.0% and 59.3% of patients on deucravacitinib hit PASI 75 versus 38.1% and 37.8% on Otezla. Of those deucravacitinib patients who hit the PASI 75 mark at six months, 82.5% and 81.4% maintained that response at the one-year check in.
Deucravacitinib showed similarly higher rates of skin clearance than placebo and Otezla with a slightly higher rate of severe side effects than Amgen’s drug.
Those side effects will be a key point of contention during the FDA’s review, given the TYK2 pathway is part of the JAK family. Bristol Myers says deucravacitinib’s high degree of selectivity means the drug doesn’t inhibit JAK1, JAK2 or JAK3, which could help the drug avoid some of that class’ severe side effects.
In September, the FDA wrapped a postmarketing safety review for Pfizer’s Xeljanz, finding an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death. That unwelcome update took a big hit out of not only Pfizer but the JAK class on the whole — including blockbuster hopefuls like AbbVie’s Rinvoq — after the FDA changed the class’ label to limit use to certain patients who are not treated effectively or who experience severe side effects with the TNF blockers.
While deucravacitinib’s chances appear good in psoriasis, breaking out into other indications could prove a challenge given some less-than-stellar results elsewhere. In October, deucravacitinib flopped a key Phase II test in ulcerative colitis, failing to spur clinical remission at three months and missing key secondary endpoints at an interim check-in.
Details on the failure were slim, but Bristol Myers is still holding out hope in this indication with another Phase II test in the works and a broad clinical program underway.