Novartis’ blockbuster cancer drug Glivec damages the heart and can cause patients to develop heart failure, according to a study published in the online edition of the journal Nature Medicine yesterday.
The authors of the study, led by Thomas Force of Jefferson Medical College in Philadelphia, describe 10 patients with chronic myelogenous leukaemia who developed severe congestive heart failure while receiving Glivec (imatinib; also sold as Gleevec), as well as studies in mice which show that imatinib treatment can interfere with the normal functioning of the left ventricle of the heart.
But they stressed that in CML patients imatinib’s clear benefits in extending survival likely outweigh the heart effects, adding that doctors need to be aware of the possible side effect in order to monitor patients taking the drug effectively, and that strategies should be identified to allow patients to stay on therapy even if symptoms develop.
Novartis said in an e-mailed statement that clinical experience with Glivec to date suggests the risk of heart failure is low, but that it was ‘committed to coducting further clinical research to ensure safe and effective use of the drug in all patients. In addition to CML, Glivec is also approved to treat a rare form of stomach cancer known as gastrointestinal stromal tumours (GIST).
Sales of the drug in the first half of this year were $1.2 billion, a rise of 16% year-on-year. It is Novartis’ second biggest selling product.
The authors of the Nature Medicine study suggest that cardiotoxicity may be a direct consequence of imatinib’s mechanism of action in blocking the tyrosine kinase enzyme ABL, which while central to the disease process in CML also seems to play a role in keeping heart cells healthy.
To back up this view, they demonstrated that imatinib caused damage to heart muscle cells with normal ABL, but left cells with mutated forms of the enzyme unscathed.
Most worryingly, they suggest that the problem may extend to other drugs that inhibit tyrosine kinases, one of the most fertile areas of research in cancer at the moment as the enzymes are involved in ‘secondary messenger’ processes for cancer growth factors.
Six cancer drugs that inhibit various tyrosine kinases are already on the market, including Glivec, Pfizer’s Sutent (sunitinib), Bristol-Myers Squibb’s Sprycel (dasatinib), AstraZeneca’s Iressa (gefitinib), Bayer/Onyx' Nexavar (sorafenib) and Roche’s Tarceva (erlotinib), while dozens more are in development.