Incyte’s latest attempt to diversify away from Jakafi has drawn a blank, with the investigational Jak 1 inhibitor itacitinib failing in the Gravitas-301 study in acute graft-versus-host disease. The trial had enrolled steroid-naive subjects, and had aimed to show at least a 16-point response rate improvement over control, but in the event the 74.0% response for itacitinib plus steroids beat steroids alone by only 7.6 points (p=0.08). True, the setback might not be immediately disastrous for Incyte as this was a tough setting, especially since Gravitas-301 allowed patients to cross over to Jakafi, which is approved in second-line acute GVHD. However, it puts additional pressure on the company’s R&D machine, whose next test will be the FGFR1-3 kinase inhibitor pemigatinib in bile duct cancer. Itacitinib still has a shot at chronic GVHD, where it is being studied in the Gravitas-309 trial, though Kadmon’s KD025 is looking especially strong in this setting. Evercore ISI analysts yesterday went as far as to suggest that Incyte, capitalised at $19bn, now risked being bought and asset-stripped purely for the Jakafi cash flow.
Incyte’s GVHD trials
|Acute GVHD||Chronic GVHD|
|First line: itacitinib||Gravitas-301 (NCT03139604): itacitinib vs placebo, failed Jan 2020||Gravitas-309 (NCT03584516): itacitinib vs placebo, primary completion 2023|
|Second line: Jakafi||Reach1 (NCT02953678): single-arm study, accelerated approval May 2019||
Reach3 (NCT03112603): Jakafi vs best available therapy, results 2020
|Reach2 (NCT02913261): Jakafi vs best available therapy, succeeded Oct 2019|
|Source: Company presentation & clinicaltrials.gov|