Novartis Jakavi meets primary endpoint in study of acute graft-versus-host disease
New Delhi: Novartis recently announced positive topline results from the Phase III REACH2 study evaluating Jakavi (ruxolitinib) in patients with steroid-refractory acute graft-versus-host disease (GvHD). The study met its primary endpoint of superior overall response rate (ORR) at day 28 of treatment with Jakavi, compared with best available therapy (BAT). ORR is a standard measure of patient response to therapy.
No new safety signals were observed in REACH2; adverse events attributable to treatment were consistent with the known safety profile of Jakavi. Jakavi is approved for use in various haematological indications in more than 100 countries around the world.
Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF. Jakavi is approved in 101 countries for patients with MF, including EU countries, Switzerland, Canada, Japan and in more than 75 countries for patients with PV, including EU countries, Switzerland, Japan and Canada. The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.
Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the United States. Jakavi is marketed in the United States by Incyte Corporation as Jakafi for patients with PV who have had an inadequate response to or are intolerant of hydroxyurea, for patients with intermediate or high-risk MF, and steroid-refractory acute GvHD in adult and pediatric patients 12 years and older.
Commenting on the same, John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis said, “As many as half of haematopoietic stem cell transplant recipients develop acute GvHD."
“We are delighted that Jakavi showed such promise in this very difficult condition especially since few second-line treatment options exist. These impressive results will be part of our regulatory submissions seeking approval in Europe and other countries, ” he added.
Novartis expects to present the full REACH2 results at an upcoming medical congress and will initiate discussions with ex-U.S. regulatory authorities in 2020. Earlier this year, the U.S. FDA approved ruxolitinib for the treatment of steroid-refractory acute GvHD in adult and pediatric patients 12 years and older based on results of the single-arm Phase II REACH1 trial. The Phase III REACH3 study in patients with steroid-refractory chronic GvHD is ongoing and results are expected next year. The REACH studies are part of the largest registration trial program in patients with steroid-refractory acute and chronic graft-versus-host disease to-date.
The recommended starting dose of Jakavi in PV is 10 mg given orally twice daily. The recommended starting dose of Jakavi in MF is 15 mg given orally twice daily for patients with a platelet count between 100,000 cubic millimetres (mm) and 200,000 mm, and 20 mg twice daily for patients with a platelet count of >200,000 mm. Doses may be titrated based on safety and efficacy. There is limited information to recommend a starting dose for MF and PV patients with platelet counts between 50,000/mm and <100,000/mm. The maximum recommended starting dose in these patients is 5 mg twice daily, and patients should be titrated cautiously.
Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation. The safety and efficacy profile of Jakavi has not yet been established outside of its approved indications.