New research from Eli Lilly ( LLY) demonstrates the difficulty that doctors, patients and, yes, investors face in balancing the benefits and risks of a drug. The drug is Evista, an osteoporosis medication that Lilly is testing as a treatment for invasive breast cancer. In a report from the The New England Journal of Medicine, a Lilly-sponsored study shows that Evista reduced the risk of breast cancer but also increased the chance of fatal strokes and the development of blood clots in the legs and lungs. "What level of breast-cancer risk would justify the use of
Evista for the prevention of breast cancer for a given person, if one takes into account the competing risks and patient preferences?" asks Marcia L. Stefanick of the Stanford School of Medicine's prevention research center. "Complicating the answer is our inability to predict these risks with high accuracy on an individual basis." Stefanick's comments appeared Thursday in an editorial accompanying the study. Lilly hasn't commented on when it might seek Food and Drug Administration approval of Evista as a breast-cancer treatment, although the company has said it would file an application . Evista was approved by the FDA in late 1997 for osteoporosis. Evista is Lilly's fourth-largest drug, although its sales grew only 2% to $1.04 billion last year. Getting the FDA's approval for breast cancer would theoretically broaden the drug's sales prospects, but Albert Rauch, an analyst with A.G. Edwards, isn't so sure Lilly would make big gains. Even if the FDA grants approval, several other drugs on the market "have shown better efficacy, and we question Evista's ability to significantly" capture market share, he wrote in a research note. The other drugs include Arimidex from AstraZeneca ( AZN), Femara from Novartis ( NVS) and Aromasin from Pfizer ( PFE). Rauch, who has a buy rating on Lilly, doesn't own shares. His firm doesn't have an investment-banking relationship.
The Lilly study surveyed 10,101 post-menopausal women with an average age of 67.5 years, looking for cardiovascular side effects and the drug's impact on breast cancer. Participants had heart disease or symptoms of heart disease. The participants received Evista, whose scientific name is raloxifene, or a placebo. The median treatment period was 5.6 years. Patients were enrolled between June 1998 and August 2000. Researchers said Evista "did not significantly affect" the risk of heart disease. Although the drug did reduce the risk of breast cancer and vertebral fracture, it also raised the risk of fatal stroke and blood clots in veins. The authors concluded that if doctors prescribe Evista, they must "take into account the individual woman's risk of disease and her personal preferences and weigh potential benefits against risks and against the availability of alternative interventions." All of the study's authors, including lead author Dr. Elizabeth Barrett-Connor of the University of California-San Diego, have received consulting fees, grants or other financial support from Lilly and several other drug companies. Two authors are Lilly employees. When the study was being designed, the authors note that there was "compelling evidence from many observational studies" that post-menopausal estrogen therapy could provide heart benefits. Then, three big clinical trials of postmenopausal treatment with hormones failed to show any benefit. Another study of two hormones "showed an early increased risk" of heart problems, the authors say. "For now, there is no magic bullet that can reduce the risks of major health problems related to estrogens and aging without introducing other potentially serious health concerns," says the editorial in The New England Journal of Medicine. The latest study adds to the risk-benefit debate of Evista and other breast-cancer drugs. In April, the National Cancer Institute issued preliminary results for a comparison between Evista and tamoxifen, a breast-cancer drug that has been available for nearly 30 years. The institute said Evista was equal to tamoxifen in reducing the risk of invasive breast cancer in post-menopausal women, but Evista caused fewer blood clots and cataracts.
Generic tamoxifen's label carries a black box warning -- the strongest alert from the FDA -- that says uterine cancer, stroke and blood clots can occur two to four times more often in patients receiving tamoxifen than in those receiving a placebo. The label says these side effects occur in fewer than 1% of women. Although the Evista label warns about blood clots and other side effects, it doesn't carry a black box warning. When the National Cancer Institute report was released, a top Lilly executive called it "an important milestone in cancer research" and the acting director of the NCI said the study represents "a significant step in breast cancer prevention." The NCI spent $88 million on the study and Lilly contributed $30 million. Final results were published in early June in The Journal of the American Medical Association. If the FDA approves Evista for preventing invasive breast cancer, the authors say, "primary care physicians may be more willing, given their experience with
Evista , to prescribe it for breast cancer chemoprevention than they have been to prescribe tamoxifen."