Novartis has reported that findings from three large, randomized Phase III studies demonstrate the superiority of Tasigna (nilotinib) to  Gleevec (imatinib mesylate) tablets at achieving deeper molecular responses across various Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) patient populations, including newly diagnosed patients, patients with residual disease who switched to Tasigna after long-term treatment with Gleevec, and patients who failed to respond to frontline Gleevec (as defined by 2013 European LeukemiaNet [ELN] guidelines). These results were presented in oral sessions at the 55th annual meeting of the American Society of Hematology (ASH) in New Orleans.

The five-year ENESTnd data, presented at ASH, continued to support the use of Tasigna in newly diagnosed Ph+ CML patients and demonstrated higher rates of early and deeper sustained molecular response, including MR4.5, and a reduced risk of progression compared to Gleevec. The difference in the rates of both MR4 and MR4.5 continued to be higher for both Tasigna 300 mg and 400 mg twice daily arms compared to Gleevec. Data indicated a trend for higher overall survival (OS) and event-free survival (EFS) rates in patients treated with Tasigna compared to patients treated with Gleevec. Fifteen patients treated with Gleevec had CML-related deaths, compared to six and four patients on the Tasigna 300 mg and 400 mg twice daily arms, respectively. Few new adverse events (AEs) and laboratory abnormalities were observed between four and five years. Rates of patients with AEs leading to discontinuation were 11.1%, 17.7% and 13.2% in the Tasigna 300 mg twice daily, Tasigna 400 mg twice daily and Gleevec arms, respectively.

In a separate follow-up analysis, results from the 36-month ENESTcmr data continued to show that Ph+ CML patients with residual disease following long-term treatment with Gleevec achieved deeper molecular responses** after switching to Tasigna. Among patients without documented MR4.5 at baseline, cumulative incidence of MR4.5 was higher in patients randomized to Tasigna versus Gleevec. MR4.5 was achieved faster with median time to response of 24.0 months in the Tasigna arm and was not reached in the Gleevec arm. The safety profiles for Tasigna and Gleevec were consistent with prior studies. By 36 months, no patients in either arm progressed to accelerated phase/blast crisis (AP/BC).

Novartis also presented results from the LASOR study, which demonstrated higher rates of molecular response in patients who failed to achieve a cytogenetic response (CCyR) with frontline Gleevec (patients who do not achieve CCyR by six months, have loss of response at any time or have intolerance) who switched to Tasigna, versus those who dose escalated on Gleevec (600 mg daily). The primary endpoint of CCyR at six months after randomization, which was confounded by high rates of crossover to Tasigna from the Gleevec arm, did not achieve statistical significance, but the company contends the clinical benefit of Tasigna was best evaluated when considering cross-over patients as non-responders. A sensitivity analysis conducted supported the efficacy of Tasigna over Gleevec. The safety profile for both drugs was consistent with prior reports of patients who switched therapy after inadequate responses to Gleevec.