Incyte’s hope of developing Jakafi as a therapy for solid tumours has been dashed after a failed phase III trial in pancreatic cancer.
In the JANUS 1 trial, JAK1/JAK2 inhibitor Jakafi (ruxolitinib) failed to show a significant benefit when given alongside Roche’s Xeloda (capecitabine) as a second-line treatment for patients with advanced or metastatic pancreatic cancer.
This is the second disappointing trial of the efficacy of Jakafi in cancer treatment in recent weeks. In January, Incyte announced that a phase II trial of the drug given in tandem with Bayer’s Stivarga (regorafenib) as a treatment for patients with relapsed or refractory metastatic colorectal cancer also failed to show efficacy.
Incyte had been encouraged to start trials of Jakafi in solid tumours on the back of the phase II RECAP study, which suggested a survival benefit for the drug in a subgroup of pancreatic cancer patients with elevated levels of a biomarker for systemic inflammation called C-reactive protein (CRP).
With two failed trials, Incyte has now decided to discontinue all other studies of Jakafi in solid tumours, including two phase II trials in breast and lung cancer. Incyte said that a phase II trial in pancreatic cancer of a follow-up drug – selective JAK1 inhibitor INCB39110 – has also been halted.
“We have … decided to stop all ongoing clinical trials that are based on the systemic inflammation hypothesis”, said Richard Levy, Incyte’s chief drug development officer.
He added that the company is not however abandoning efforts to develop selective JAK1 inhibitors in solid tumours and would continue to develop Jakafi for other haematological indications.
INCB39110 is also being tested in combination with other drugs in solid tumours – including Merck & Co’s PD-1 inhibitor Keytruda (pembrolizumab) as well as Incyte’s IDO1 inhibitor epacadostat and PI3K delta inhibitor INCB50465. In these trials the hypothesis is that the drug will have a synergistic effect in reducing tumour resistance to the immune response.
Jakafi is already a successful product for Incyte in its approved indications of polycythemia vera and myelofibrosis, bringing in $182m in direct sales for the company in the fourth quarter as well as $24m in royalties from licensee Novartis.
The two companies sold $1bn-worth of the product in 2015 as a whole, with Incyte sales accounting for $600m of the total, and the company expects its revenues from the product to reach more than $800m this year.
Nevertheless the failure to tap into the solid tumour market has pegged back peak sales projections for Jakafi and has spooked investors. Shares in the company fell by almost a quarter yesterday before ending the day down a little over 9%.
The company is now expecting peak sales of around $1.5bn in haematological indications.