A new oral drug to treat chronic myeloid leukaemia has been approved in record time by the US Food and Drug Administration.
At a news conference in Washington, DC, attended by the US secretary of health and human services, Tommy Thompson, and the director of the National Cancer Institute, Dr Richard Klausner, the administration announced its approval of imatinib mesylate (Gleevec).
The new drug, manufactured by Novartis of Basle, Switzerland, was approved after a review of the clinical data lasting only two and a half months. The drug has also proved effective against rare gastrointestinal stromal tumours and small-cell lung cancers. Imatinib mesylate has been developed during 16 years of research that began in 1985 at Ciba-Geigy, a predecessor of Novartis.
To date, the new drug has been studied in more than 7500 patients at 490 sites in 30 countries. According to the National Cancer Institute, it was designed in the laboratory to target an abnormal version of a normal cellular protein, present in nearly all patients with chronic myeloid leukaemia.
The abnormal protein is much more active than the normal protein and is probably the cause of the disease. By blocking the abnormal protein, BCR-ABL, the drug kills the leukaemia cells.
Imatinib mesylate represents a new class of cancer drugs and a new way of thinking about cancer. These molecularly targeted drugs are different from earlier drugs because they target abnormal proteins that are fundamental to the cancer itself.
Imatinib mesylate and other drugs in development are designed to target the specific molecules that cause cancer while avoiding serious damage to other, non-cancerous cells. Given the success of the drug and the recent explosion of powerful molecular technology, scientists are searching intensively to discover the correct targets in other cancers.
In clinical trials the white blood cell counts of 88% of patients with chronic myeloid leukaemia returned to normal. In 49% of patients the so-called "Philadelphia chromosome" (which causes the production of BCR-ABL) either disappeared or reduced significantly.
The latest study, by Dr Brian Druker and colleagues from the Oregon Health Sciences University, Portland, showed that imatinib mesylate restored normal blood counts in 53 out of 54 patients whose chronic myeloid leukaemia was resistant to chemotherapy—a response rate rarely seen in cancer with a single agent (New England Journal of Medicine 2001;344:1031-37).
Most of those treated with the drug experienced adverse events at some time. In clinical trials these were nausea (55-68% of patients), fluid retention (52-68%), muscle cramps (25-46%), diarrhoea (33-49%), vomiting (28-48%), haemorrhage (13-48%), musculoskeletal pain (27-39%), skin rash (32-39%), headache (24-28%), and fatigue (24-33%).
More serious side effects included raised liver enzymes (1.1-3.5%); severe superficial oedema (1-5%); and haemorrhages (0.4-16%). Novartis said that the drug would cost $2000 to $2400 (£1430-£1710) a month but that it would supply the drug for less to patients not covered by insurance.
Further information about clinical trials with imatinib mesylate is available at http://cancertrials.nci.nih.govhttp://cancertrials.nci.nih.gov