Avastin Combo Trials Stopped Over Adverse OutcomesJul 15, 2008 | Parker Waichman LLP
Genentech Inc., has just sent out a written warning to doctors about a type of anemia seen in patients treated with its popular cancer drug Avastin—bevacizumab—when taken with Pfizer Inc.'s Sutent in a clinical trial. The cases of microangiopathic hemolytic anemia (MAHA) seen in a Phase 1 kidney cancer study prompted the closure of a mid-stage trial of Avastin plus Sutent, Genentech said in a letter to doctors posted on the Food and Drug Administration's (FDA) website.
The Avastin-Sutent combination is neither approved nor recommended according to the Genentech letter. Avastin, stops blood supply to tumors and is approved to treat colon, lung, and breast cancer. Sutent—generically known as sunitinib malate—is one of the most widely used medicines for the treatment of advanced kidney cancer. Avastin, considered Genentech's most important product, is being tested in combination with other drugs in a variety of clinical trials.
The letter noted that five of 12 patients who received the highest Sutent dose had laboratory findings consistent with microangiopathic hemolytic anemia. In the study, 25 patients were studied and groups were given Sutent in escalating doses in a four week on and two week off schedule. Two cases were considered severe with evidence of several adverse side effects, including—but not limited to—severe high blood pressure. Genentech spokeswoman Kimberly O'Campo said other studies combining lower doses of Sutent with Avastin are ongoing.
Meanwhile, two other mid-stage studies of Avastin in combination with Sutent and chemotherapy were stopped over poor tolerability involving fatigue, gastrointestinal complications—diarrhea, anorexia, dehydration, and stomatitis—and myelosuppression, which is a condition in which blood cell and platelet production is reduced. O’Campo noted that those trials involved patients with breast and lung cancer.
Analysts are looking for second-quarter U.S. Avastin sales of over $640 million when Genentech announces its quarterly results this week. Genentech shares were down $2.36, or 3 percent, to $75.39 on the New York Stock Exchange.
Avastin is prescribed as a last beacon of hope in often hopeless situations. But, Avastin does not come cheap, can run around $100,000 annually, is not without controversy. Studies show Avastin only prolongs life by a few months, if that. Newer studies suggest the drug might be less effective against cancer than the FDA understood when it first approved Avastin. While many patients and their doctors say the drug can improve the quality of life by providing intangibles such as a sense of well-being and an ability to carry out daily tasks without exhaustion or pain, these benefits are difficult to monitor and document. And, now, many patients with other cancers are taking Avastin, despite that there is no compelling evidence that helps. Avastin also has serious, sometimes lethal side effects.
Avastin is generally used in conjunction with standard chemotherapy and does not work as well when used alone, meaning that patients are still subject to chemotherapy’s side effects. Also, Avastin’s cost to patients and insurers can be higher because doctors and hospitals buy Avastin and then sell it to patients or their insurers, often marking up the price.