The first Phase III trial to directly compare Novartis’ chronic myeloid leukemia (CML) drugs Tasigna® and Glivec® (known as Gleevec in the U.S.) found Tasigna produced faster and deeper responses when given as first-line therapy to adult patients with newly diagnosed Philadelphia chromosome-positive CML (Ph+ CML) in the chronic phase. Novartis claims the trial was also the first registrational study to use molecular traces of the Bcr-Abl marker specific to Ph+ CML as a primary endpoint for regulatory review.
Tasigna is currently only approved for treating Ph+ CML in adult patients resistant or intolerant to at least one prior therapy including Glivec.
The trial was designed to compare the major molecular response (defined as a thousandfold or more reduction in Bcr-Abl relative to standardized baseline level) in patients treated for 12 months with either drug. In addition to meeting its primary endpoint, the study also met its secondary endpoint of an improved complete cytogenetic response (CCyR) among Taisgna-treated patients at 12 months.
“We developed Tasigna to be a potent and selective inhibitor of Bcr-Abl with the goal of eliminating the underlying cause of Ph+ CML,” comments David Epstein, president and CEO of Novartis oncology and Novartis molecular diagnostics. “We now know that Taisgna reduces the level of Bcr-Abl faster and to a lower level than Glivec. Molecular monitoring enables us to evaluate whether patients have achieved this deep level of CML residual disease, reducing the fundamental biomarker of leukemia to nearly undetectable levels.”
The blood-based test to determine molecular response can detect one in a million cells containing traces of the Bcr-Abl marker of residual disease, according to Novartis. The company states that in addition to being simpler and less invasive for patients, the molecular assay is more sensitive than standard cytogenetic tests, which require a bone marrow sample to visually detect cells containing the Ph chromosome.
Glivec is approved in over 90 countries as first-line therapy for certain forms of CML and gastrointestinal stromal tumors (GIST). In May the drug received European regulatory approval as a post-surgery therapy for GIST on the back of equivalent approvals in Switzerland in February and the U.S. in December 2008. Novartis reported worldwide Glivec/Gleevec sales of $1.9 billion during the first half of 2009, up 15% in local currencies from the same period in 2008.
Tasigna is approved in 73 countries as a second-line therapy for chronic phase and accelerated phase Ph+ CML in adult patientsc. US and European approvals for Tasigna were granted in late 2007. The drug achieved worldwide sales of $88 million in the first half of this year.