ROCKVILLE, MarylandFDA has granted accelerated approval to Novartis' Tasigna (nilotinib) capsules for the treatment of chronic phase and accelerated phase Philadelphia chromosome positive chronic myelogenous leukemia in adult patients who are resistant or intolerant to prior therapy that included imatinib (Gleevec). FDA said that the approval is based on hematologic and cytogenetic response rates rather than clinical benefit, such as improvement in disease-related symptoms or increased survival. Novartis must submit further follow-up data from an ongoing study in order to convert from accelerated approval to regular approval.
"The FDA approval of Tasigna is a very significant step forward. Tasigna is a highly specific potent inhibitor of Bcr-Abl, which is the kinase that drives CML," said investigator Francis Giles, MD, of the University of Texas Health Science Center, San Antonio.
Applying experience gained from the development of Gleevec, a team of Novartis scientists created Tasigna in August 2002, just a year after the launch of Gleevec. Tasigna was specifically designed to target the Bcr-Abl protein more preferentially than Gleevec, without adding new targets (see Figure). In preclinical studies, it was active against 32 of 33 imatinib-resistant cell lines with Bcr-Abl mutations.
"Results with Gleevec are great," said Jorge Cortes, MD, a Tasigna investigator from M.D. Anderson Cancer Center, "but we always want to have options. With Tasigna, you have the peace of mind that most of your patients will do well on Gleevec, but for the ones who do not, you have something good to offer."
Approval was based on an ongoing open-label nonrandomized multicenter clinical trial in which patients received Tasigna at a starting dose of 400 mg twice daily. At the time of data cut-off, 232 CML-CP (chronic phase) patients and 105 CML-AP (accelerated phase) patients were evaluable for efficacy. All patients had received prior imatinib, and many had received hydroxyurea (85%), interferon (62%), and bone marrow transplantation (8%).
Imatinib was discontinued in 73% of patients because of resistance and in 27% because of drug intolerance. The highest prior maximum imatinib dose was 600 mg/d or higher in 77% of patients, with 44% of patients receiving doses of 800 mg/d or higher.