FDA has approved Novartis’ Tasigna® as first-line therapy for adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in the chronic phase. Novartis says regulatory submissions for use of Tasigna as first-line therapy against Ph+ CML are in progress worldwide, and applications have been filed in the EU, Switzerland, and Japan.
FDA approval followed a priority review by the agency and was based on data from the Phase III ENESTnd study. Results from the trial were also published in The New England Journal of Medicine today in a paper titled “Nilotinib versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia.”
Tasigna was first sanctioned in 2007 for the treatment of chronic phase and accelerated phase Ph+ CML in patients resistant to or intolerant to at least one prior therapy including Gleevec. “It’s important for companies to continue developing oncology drugs for earlier stages of the disease once they have demonstrated clinical effectiveness in resistant forms of cancer,” comments Richard Pazdur, M.D., director of the Office of Oncology Drug Products, which is part of FDA’s Center for Drug Evaluation and Research.
Tasigna is designed as a selective inhibitor of Bcr-Abl. The open-label ENESTnd trial directly compared the efficacy and safety of treating 846 newly diagnosed cases of Ph+ CML using either one of two doses of Tasigna or Novartis’ other CML drug, Glivec®. The overall results showed that Tasigna eliminated Bcr-Abl faster than Gleevec and resulted in lower rates of cancer progression, even within the first 12 months.
At 12 months the rates of major molecular response were 44% for patients given the 300 mg dose of Tasigna and 43% for those treated using 400 mg, Novartis reports. The major molecular response for patients treated using Gleevec was 22%.
The rates of complete cytogenetic response (CCR) by 12 months were also significantly higher for patients treated using Tasigna. CCR reached 80% for those receiving 300 mg Tasigna, 78% for those on the 400 mg dose, but 65% for Gleevec-treated patients.
Patients receiving either dose of Tasigna twice daily also demonstrated a significant improvement in the time to progression to the accelerated phase or blast crisis, report authors Giuseppe Saglio, M.D., at the University of Turin’s San Luigi Gonzaga Hospital in Orbassano, and colleagues. They also note that none of the patients with progression to the accelerated phase or blast crisis had a major molecular response.
Gleevec was Novartis’ second best-selling pharmaceutical in 2009, with sales reaching nearly $4 billion, up 12% in local currencies on 2008 figures. 2009 also saw Gleevec approved for use in the adjuvant, post-surgical treatment of gastrointestinal stromal tumors (GIST). Tasigna achieved sales of $212 million in 2009, up 145% on 2008 figures. The drug is separately undergoing Phase III trials in patients with GIST.
In December 2009, Novartis confirmed plans to start a Phase III study evaluating Tasigna in patients with cKit-mutant melanoma during this year. Studies in patients with pulmonary arterial hypertension are ongoing.