Data published today in the New England Journal of Medicine underpinned Gleevec(R) (imatinib mesylate) tablets as a durable and well-tolerated long-term therapy for newly diagnosed adult patients with a form of blood cancer known as Philadelphia chromosome- positive (Ph+) chronic myeloid leukemia (CML).

According to the publication, the five-year overall survival of patients who received Gleevec as initial therapy is higher -- estimated at 95% when excluding deaths from causes unrelated to CML or prior transplantation -- than that in any previously published prospective study of the treatment of CML, a disease with limited survival options before the approval of Gleevec.

Results of the International Randomized Interferon versus STI571 (IRIS) study -- the largest clinical trial ever for this patient population -- showed that responses to therapy with Gleevec continued to increase substantially over five years, while the yearly risk of progression to advanced disease declined to 0.6% in the fifth year.

"These data underscore that Gleevec continues to support positive outcomes in CML with the opportunity for patients to achieve better outcomes the longer they take the therapy," said David Epstein, president and CEO of Novartis Oncology. "The five-year data also show that Gleevec offers very good tolerability as well as an established and predictable safety profile."

The overall survival rate for patients receiving Gleevec was 89% (range 86% to 92%) when considering deaths from all causes. However, when deaths from causes unrelated to CML or prior transplantation are excluded, the overall survival rate was 95% at 60 months.

Before Gleevec was available, about 50% of patients progressed to the more advanced stages of Ph+ CML after only three to five years, and survival was generally short for those patients.

Gleevec has continued to be generally well-tolerated as initial drug therapy for Ph+ CML in chronic phase at the five-year follow-up. With a median follow-up of 60 months, the adverse events were similar to the previously reported profile. Newly occurring or worsening grade 3 or 4 hematologic or biochemical adverse events were infrequent after two and four years of therapy.

Most recently, Gleevec was approved in the European Union (EU) for the treatment of patients with the rare life-threatening blood disorders myelodysplastic syndromes/myeloproliferative diseases (MDS/MPD) and hypereosinophilic syndrome/chronic eosinophilic leukemia (HES/CEL). Gleevec was also recently approved in the EU for adult patients with newly diagnosed Ph+ acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy and as a single agent for patients with relapsed or refractory Ph+ ALL, and in the US for relapsed/refractory Ph+ ALL.

In only five years, Gleevec has now been approved in the EU for six diseases, including two solid tumors and four blood disorders with molecular targets known to be inhibited by the drug. In the US, Gleevec has now been approved for seven diseases, including two solid tumors and five blood disorders with molecular targets known to be inhibited by the drug.

IRIS study details

The International Randomized Interferon versus STI571 (IRIS) study is an open-label Phase III clinical trial enrolling 1,106 newly diagnosed patients with Ph+ CML in chronic phase in 177 centers across 16 countries. There are two arms to the study: one group of patients receiving Gleevec 400 mg per day and another receiving a target dose of interferon (IFN) of 5 MIU/m2/day in combination with Ara-C 20 mg/m2/day for 10 days each month. Because of tolerability reasons, lack of response, or loss of response, 65% of patients in the IFN/Ara-C arm crossed over to the Gleevec arm, whereas only 3% of patients in the Gleevec arm crossed over to the IFN/Ara-C arm.

Cumulative best responses to Gleevec treatment improved dramatically between the first and fifth years of treatment. Over the period, major cytogenetic responses rose from 85% to 92% and complete cytogenetic responses rose from 69% to 87%. Complete hematologic responses rose from 96% to 98%. In a complete hematologic response, the patient's blood cell counts return to normal. Cytogenetic response refers to the disappearance or reduction of the number of Ph+ cells detectable by standard lab methods.

About Gleevec Tablets

Gleevec(R) (imatinib mesylate) tablets are indicated for the treatment of newly diagnosed adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. Follow-up is limited. Gleevec tablets are also indicated for the treatment of patients with Ph+ CML in blast crisis, in accelerated phase, or in chronic phase after failure of interferon- alpha (IFN-a) therapy.

Gleevec tablets are also indicated for the treatment of patients with KIT (CD117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST). The effectiveness of Gleevec in GIST is based on objective response rate. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.

Gleevec tablets are also indicated for the treatment of adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP), relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), certain forms of myelodysplastic/myeloproliferative diseases (MDS/MPD), hypereosinophilic syndrome and/or chronic eosinophilic leukemia (HES/CEL) and aggressive systemic mastocytosis (ASM).

Important Safety Information(1)

Hematologic Disorders

For Ph+ CML, severe (NCI Grades 3/4) lab abnormalities-including neutropenia (3%-48%), anemia (