Monday, July 30, 2001

FDA Panel Okays Osteoporosis Drug for Women

BETHESDA, MD (Reuters Health) - A US Food and Drug Administration (FDA) advisory panel on Friday unanimously recommended that the agency approve Eli Lilly's new parathyroid hormone injection Forteo for the treatment of osteoporosis in postmenopausal women. But the panel split 5- 5 on approving the drug for increasing bone density in men with the disease. The FDA often, but not always, follows the advice of such panels when approving a drug for marketing.

- 2001/07/30

By Todd Zwillich At the same time, experts unanimously agreed that data from Lilly's pivotal trials did not sufficiently support the safety of Forteo in either women or men. Panelists and FDA officials expressed concern about high rates of a deadly form of bone cancer known as osteosarcoma in laboratory animals exposed to the drug. If approved, the drug, known as teriparatide, will be the first hormonal treatment targeted specifically for the ability to form new bone in patients suffering from the bone-wasting disease osteoporosis. Panelists were encouraged by the drug's performance in protecting older women from bone fractures. Women on Forteo showed a 65% reduced risk of spinal fractures versus women who received an inactive placebo during a 19-month study. Women on the drug also had significantly improved bone mineral density scores, while women on the placebo showed slight declines in bone density during the trial. Dr. Mark Molich, the committee's acting chair, called Forteo's apparent ability to build bone ``impressive.'' The company also showed that the same dose could increase bone mineral density in the spine by over 5% in 437 men who took it for 6 months. Panelists split on approving the efficacy of the drug in men, primarily because of a lack of data showing the drug can actually help prevent bone fractures in older men. Lilly senior researcher Gregory A. Gaich said that the most common side effects were nausea, leg cramps and headaches, experienced in 3% to 9% of patients who took active injections. The drug also caused some rises in blood and urine calcium levels shortly after dosing. ``These transient changes in serum calcium were small,'' Gaich said. But panelists focused their attention on previous laboratory studies showing that the drug drastically increased cancer rates in rats. Animals studied by Lilly had a risk of osteosarcoma that was between 29 and 225 times higher than normal, depending on the dose of Forteo. The discovery prompted Lilly to stop its Forteo trials in humans ahead of schedule. Company researchers stressed that no humans in their studies developed osteosarcoma. They argued that rat biology and physiology were different from humans and that a high rate of cancer in the animals did not translate to the risk of a high rate in humans. But agency scientists remained skeptical because they have no studies showing humans' reactions will be any different from those of lab animals. The only study testing the cancer risk in monkeys--a species considerably closer to humans physiologically--went on for only 18 months and was considered inconclusive. ``We cannot exclude that there is a potential increased risk of bone neoplasm (cancer) in humans treated with teriparatide,'' said Dr. Gemma Kuijpers, an FDA official who reviewed the study data. ``The tumor findings are likely to be relevant'' to humans, she said. Company officials said that if allowed to market Forteo, they would recommend that physicians limit its use to 2 years in each patient. ``That is what the data support,'' said Bruce H. Mitlak, the director of the Forteo product team at Lilly. The company also said that it would recommend that patients at risk for osteosarcoma, including those with Paget's disease, and all children avoid the drug. Paget's disease occurs most often in old age, causing bones to weaken, thicken and become deformed. Panelists were adamant that the FDA condition its approval on the formation of strict post-marketing studies or patient registries so that the company and the government can track any bone cancer cases that arise from use of the drug. Panelists also recommended package warnings to alert doctors and patients about the laboratory cancer evidence. FDA officials warned that low overall rates of osteosarcoma, which occurs naturally in about 4 per 1 million persons, will make it difficult for researchers to pick up any cases potentially caused by the drug. ``We need to be clear that we're talking about a large element of uncertainty that will go on for a protracted period of time even if we do the very best we can,'' said FDA scientific reviewer Bruce V. Stadel.

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