Tasigna Approved for Gleevec-Resistant Chronic Myeloid Leukemia

October 29, 2007

The Food and Drug Administration approved Tasigna (nilotinib) as a new anti-cancer therapy for certain patients with a life-threatening form of leukemia who are resistant or intolerant to prior treatment including Gleevec (imatinib), an established treatment standard.  

Tasigna should be available within days throughout the United States for patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML), one of the four most common types of leukemia, which affects around 4,500 people in the country each year.  

Tasigna works by inhibiting the proliferation of cells containing an abnormal chromosome. It does this by targeting the production of the Bcr-Abl protein, which is produced only by cells containing the abnormal Philadelphia chromosome. This protein is recognized as the key cause and driver of the overproduction of cancer-causing white blood cells. Tasigna was specifically designed to target the Bcr-Abl protein more preferentially than Gleevec without adding new mechanisms of action.

At six months follow-up, Tasigna reduced or eliminated cells carrying the abnormal Philadelphia chromosome in 40 percent of patients in chronic phase of the disease. Applying experience gained from the development of Gleevec, which remains the most frequently prescribed treatment for patients with CML, a team of scientists created Tasigna in 2002, just a year after the launch of Gleevec.

In preclinical studies, the medicine was able to overcome resistance resulting from Bcr-Abl kinase mutations in 32 of 33 cell lines commonly associated with Ph+ CML. Patients with a variety of these mutations also responded to treatment with Tasigna.  

Without treatment, CML typically progresses over three to five years from the initial (chronic) phase through a transition period (accelerated phase) to a rapidly fatal form (blast crisis). Recent landmark clinical trial results for Gleevec show that nearly 90 percent of newly diagnosed chronic-phase Ph+ CML adult patients treated with Gleevec were alive after five years, but some develop resistance or cannot tolerate this therapy.  

The FDA approved Tasigna for treatment of chronic-phase and accelerated-phase Ph+ CML in adult patients resistant or intolerant to prior treatment, that included Gleevec.  This approval is based on an open-label multicenter clinical trial evaluating the drug's safety and rates of cytogenetic response (eg. reduction or elimination of the Philadelphia chromosome) and hematologic response (eg. normalization of white blood cell counts) in Gleevec-resistant or -intolerant patients with Ph+ CML in chronic phase (n=280) and accelerated phase (n=105).  

In clinical trials, the primary endpoint for patients in chronic phase was unconfirmed major cytogenetic response (MCyR). After a minimum follow-up of six months (median treatment duration 8.7 months), Tasigna produced MCyR in 40 percent of 232 chronic phase patients evaluated for efficacy. The complete cytogenetic response in these patients was 28 percent. For patients in accelerated phase, the primary endpoint was confirmed hematological response (HR). Complete HR was reported in 18 percent of patients in accelerated phase. (Accelerated phase patients had a minimum follow-up of four months and a median treatment duration of 6.4 months). In addition, 24 different mutations in Bcr-Abl were noted in 19 percent of chronic phase and 25 percent of accelerated phase CML patients who were evaluated for mutations.  

The most frequent side effects for Tasigna were primarily hematological and included neutropenia and thrombocytopenia. The most frequent non-hematologic drug-related adverse events were rash, pruritus, nausea, fatigue, headache, constipation, and diarrhea. Most of these adverse events were mild to moderate in severity.