Novartis Oncology announced that data on Glivec(TM), formerly STI571, was featured in more than 50 abstracts this week at the annual meeting of The American Society of Hematology (ASH) in San Francisco. Glivec is an investigational treatment for certain forms of leukemia. The data offer new and updated information regarding the agent's potential activity in treating certain forms of leukemia that are characterized by the presence of the Philadelphia chromosome, including chronic myeloid leukemia (CML) and, to a lesser extent, acute lymphocytic leukemia (ALL) and acute myeloid leukemia (AML).

"We are extremely encouraged by the growing body of scientific evidence on our investigational agent Glivec, and its potential role in treating certain forms of CML," said David Epstein, President, Novartis Oncology. "Novartis is committed to the ongoing study of Glivec as a vital treatment option for physicians and patients in the battle against this disease."

Clinical Data

On Monday and Tuesday, December 4th and 5th, of the more than 50 presentations taking place, 14 will be oral. Data will be presented from the four largest multicenter Phase II studies ever conducted in CML to date, including the effectiveness of Glivec in patients with each phase of CML (chronic phase, accelerated phase and blast crisis) and each phase of Philadelphia chromosome-positive acute lymphoblastic leukemia.

1. Chronic Phase Study

A Phase II Study of STI571, A Tyrosine Kinase Inhibitor, in Patients with Resistant or Refractory Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Resta D, Capdeville R, Druker B

This Phase II, open-label study evaluated STI571 in patients with Philadelphia chromosome-positive (Ph+) CML who had failed interferon. Of the 532 patients enrolled, preliminary bone marrow cytogenetic results are available for 388 patients at three months. The findings demonstrated an overall cytogenetic response rate of 37 percent. Of the responses, 13 percent were complete (0 Ph+ cells) and 23 percent were major (less than 35 percent Ph+ cells). In 290 patients who had completed six months of therapy at the time of the analysis, preliminary data suggest an overall response rate of 56 percent. Hematologic results, not currently available, will also be presented at the meeting.

2. Accelerated Phase Study

A Phase II Study of STI571 in Adult Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Accelerated Phase Talpaz M, Silver RT, Druker B, Paquette R, Goldman JM, Reese SF, Capdeville R

This Phase II study includes 234 patients with CML in the accelerated phase. The preliminary response data, as assessed by the investigators, includes 154 patients who have been treated with STI571 for at least 4 weeks. The overall hematological response rate at 4 weeks is 78 percent, including 22 patients who have achieved a complete response.

3. Blast Crisis Phase Study

A Phase II Study to Determine the Safety and Anti-Leukemic Effects of STI571 in Patients with Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Myeloid Blast Crisis Sawyers C, Hochhaus A, Feldman E, Goldman JM, Miller C, Ben-Am M, Capdeville R, Druker B

This Phase II, open-label trial includes 262 CML patients in the blast crisis phase. Preliminary data is based on 94 patients, 44 of whom received prior treatment for blast crisis and 50 of whom were untreated. In the previously untreated patients, the overall response rates were 48 percent and 47 percent at 4 and 8 weeks of therapy with STI571, respectively. In those who had received prior therapy for blast crisis, the response rates were 38 percent and 33 percent, respectively.

"We are pleased with the results we've seen with Glivec thus far. It represents a new approach to cancer therapy by targeting the specific biochemical abnormality associated with certain types of CML and other rare forms of leukemia," said David Parkinson, MD, Vice President, Clinical Research, Novartis Oncology.

Additional Presentations at ASH

In addition to the studies presented at the ASH meeting, two educational programs focused on CML and the latest findings on Glivec:

1. A New Beginning: CML and Signal Transduction Inhibition, Friday, December 1 from 12:00 p.m. to 4:00 p.m. at The Moscone Center. This symposium, sponsored by the Office of CME, UCLA School of Medicine and supported by an unrestricted educational grant from Novartis, provided a thorough understanding of upcoming, new and existing therapies. The symposium was chaired by Charles Sawyers, MD, Professor of Medicine, Molecular Biology Institute, UCLA School of Medicine. Brian Druker, MD, Professor of Medicine, Division of Hematology and Medical Oncology, Oregon Health Sciences University, a lead investigator on Glivec, presented results from the Phase I Glivec trials. Other presenters included Frederick R. Applebaum, MD, Director, Clinical Research Division, Fred Hutchinson Cancer Research Center and Head, Division of Medical Oncology, University of Washington School of Medicine; John Goldman, MD, Professor of Leukaemia and Bone Marrow Transplantation, MRC Leukaemia Research Centre, Imperial College School of Medicine, Hammersmith Hospital, London, UK; Moshe Talpaz, MD, Professor of Medicine, Chairman of Bioimmunotherapy, MD Anderson Cancer Center; Owen Witte, MD, Professor of Microbiology, Immunolgy and Molecular Genetics, UCLA School of Medicine.

2. The National Cancer Institute (NCI) Workshop, will be held on today, December 3 from 8:15 a.m. to 10:00 a.m. at the Moscone Center, will focus on the challenges and opportunities in cancer research that have been created by recent scientific and technologic advances. It will feature a presentation by Dr. Druker on Glivec, and its role in "Validating the Promise of Molecularly Targeted Therapy." Other speakers include Richard Klausner, MD, Director, NCI, and Louis Staudt, MD, PhD, Metabolism Branch, NCI.

3. The 2000 Educational Program, was held on Saturday, December 2 from 10:00 to 11:45 a.m., and again from 4:00 to 4:45 p.m. During the session, Chronic Myelogenous Leukemia: New Therapeutic Modalities, five speakers presented data on the progress of research relating to CML treatment. Moshe Talpaz, MD, MD Anderson Cancer Center, gave updates on clinical studies on Glivec. Other presenters included: Jumia Melo, MD, PhD, Hammersmith Hospital; Sante Tura, MD, University of Bologna; Hagop Kantarjian, MD, MD Anderson Cancer Center; and Sergio Giralt, MD, MD Anderson Cancer Center.

About Glivec

Glivec belongs to a new class of antiproliferative agents called signal transduction inhibitors (STIs), which have been shown to have the potential to interfere with intracellular signaling pathways that have been implicated in tumor development. Glivec is molecularly targeted to the specific chromosomal abnormality, called the Philadelphia chromosome, in chronic myeloid leukemia. The abnormal protein and chromosome may also be present, to a lesser extent, in AML and ALL. Some patients with these rare forms of leukemia have been included in the Glivec clinical trials.

Researchers are also investigating the role of Glivec in solid tumors. Novartis recently began a program of small-scale proof of concept studies in selected solid tumors with its agent Glivec, where the biological mechanisms suggest potential activity. These small-scale pilot studies are intended to establish the basis for further studies in clinical trials.

As Glivec is still in clinical development, its safety and efficacy have not yet been established, and clinical trial participants are being closely monitored. In terms of side effects, preliminary results indicate that the agent has been well tolerated to date. Side effects including nausea, muscle cramps, edemas, skin rash, diarrhea, heartburn and headache have been largely mild or moderate in intensity. Fewer than three percent of patients have experienced occurrence of rare but serious side effects such as the potential for liver toxicity, fluid retention syndrome and hemorrhages.

Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is one of the four most common types of leukemia. In the United States, there are approximately 20,000-23,000 cases of CML at any given time.

CML is a hematologic stem cell disorder caused by an acquired abnormality in the DNA of the stem cells in bone marrow. The abnormality results in a gene that produces an abnormal protein.

Although researchers do not fully understand what causes this DNA change, they do know that the abnormal protein that results disrupts the bone marrow's normally well-controlled production of white blood cells. This "deregulated" production of white blood cells leads to a massive increase in their concentration in the blood.