Baxalta and CTI Biopharma have completed their rolling regulatory submission for their myelofibrosis candidate pacritinib in the US, and are aiming for accelerated approval.
Pacritinib is an oral kinase inhibitor - targeting JAK2, FLT3 RAK1 and CSF1R - and if approved would compete directly with Incyte and Novartis' fast-growing JAK2 inhibitor Jakafi (ruxolitinib) in the chronic malignant bone disorder.
Novartis booked $291m in ex-US Jakafi sales in the first nine months of 2015 - up by around 50% on the year-earlier period - while Incyte reported $491m in sales within the US, a rise of 67%.
Baxalta and CTI are seeking approval for patients with intermediate and high-risk myelofibrosis who have low platelet counts of less than 50,000 (thrombocytopenia), a group which at the moment has no FDA-approved treatment options.
Around 18% of myelofibrosis patients are thrombocytopenic at diagnosis, but low platelet counts are typically seen in around a third of patients after a year, according to data from the Mayo Clinic in the US. Moreover, within 12 months two thirds of patients will have low red blood cell counts and 45% will require a blood transfusion as a result.
While JAK1/2 inhibitors can contribute to low cell counts, pacritinib's activity at other targets means that it is less prone to do so, according to CTI's chief executive Jim Bianco. With Jakafi and other JAK2 inhibitors, dose reductions are often needed to keep platelet and red cell counts under control.
In the PERSIST-1 trial which forms the basis of the rolling file, pacritinib achieved the primary objective of being more likely to achieve a clinically significant 35% or greater reduction in spleen volume when compared to best-available therapy (which did not include a head-to-head comparison with Jakafi).
A second trial - called PERSIST-2 - includes patients on Jakafi treatment, but data from this is not yet available, as it is only just approaching full enrolment.
"We believe that the PERSIST-2 trial could serve as a post-approval confirmatory trial if our initial … application is accepted and approved under accelerated approval," said Bianco.
Meanwhile, Baxalta and CTI are also planning to test pacritinib in a much broader patient population, including patients who have had prior Jakafi therapy and those who are on a reduced dose of Novartis/Incyte's drug, which according to CTI accounts for the bulk of patients taking Jakafi in the US.
Baxalta's former parent company Baxter licensed rights to pacritinib from CTI in 2013 in a deal valued at up to $272m.