Incyte has delivered a pair of pivotal wins for an oral JAK inhibitor in an inflammatory skin condition. But with the placebo-adjusted response rate down on phase 2, the results drew unfavorable comparisons to rival data and triggered a 15% drop in the biotech’s share price.
The JAK1 inhibitor, povorcitinib, could offer an oral alternative to biologics in multiple indications and, if approved, partly offset the loss of exclusivity of Incyte's JAKi Jakafi later this decade. Incyte took the candidate into phase 3 trials in the skin condition hidradenitis suppurativa (HS) after seeing (PDF) placebo-adjusted response rates of up to 27.7% in a mid-stage study.
Asked by analysts at recent investor events, Incyte executives declined to name the number they were targeting in the phase 3 trials but did say they expected to see a profile that is consistent with the earlier trial.
The primary endpoints looked at the number of patients who had a 50% or greater reduction in total abscess and inflammatory nodule count with no increase in abscess or draining tunnel count. In the first study, around 40% of patients on both the low and high dose met the criteria, versus around 30% on placebo. The drug and placebo figures in the second trial were around 42% and 29%, respectively.
Adjusted for placebo, the response rates at the low and high dose were 10.5% and 10.9%, respectively, in the first trial. The figure for both doses was 13.7% in the second trial. In the earlier phase 2 trial, Incyte reported placebo-adjusted results of 17.3% and 27.7%, respectively, at the low and high doses used in the pivotal studies.
Incyte saw higher placebo-adjusted results in a predefined subgroup of phase 3 patients who previously took a biologic. The biotech also found more people on povorcitinib had a 75% or greater improvement, experienced a reduction in flares and reported a more than three-point improvement on a pain scale. The overall safety profile of povorcitinib was consistent with previous data, according to Incyte.
While the biopharma called the data positive, investors were unconvinced and sent the biotech’s share price down around 15% to just $58 in early premarket trading. The drop may reflect unfavorable comparisons between the phase 3 data and both Incyte’s midphase results and the evidence on rival biologics.
UCB won approval for Bimzelx in HS after linking the biologic to placebo-adjusted response rates of 19% and 20% after 16 weeks in two phase 3 trials. Novartis’ biologic Cosentyx is also approved in the indication. Povorcitinib has the advantage of oral administration but the data leave scope to question the size of the opportunity that will be open to the small molecule.