Two FDA panels to review safety of popular bone drugs

Two advisory panels of the Food and Drug Administration will consider on Friday whether to recommend requiring women who use popular bone drugs like Fosamax to take “drug holidays” because of rising concerns about rare side effects with long-term use, according to people involved in the review.

The panels and FDA staff members are also expected to conduct a comprehensive safety review of the medical evidence to date, after 16 years of growing use of the drugs, to determine whether they have proved to be safe and effective in use longer than three to five years. The recommendation could affect many of the estimated 4 million women in the United States who take the drugs, called biphosphonates. Biphosphonates inhibit a bone renewal process called resorption, adding bone mass, but possibly causing brittleness as well.

Fosamax was first approved in 1995 to treat postmenopausal osteoporosis and Paget’s disease of the bone, conditions that weaken bones. It has also been marketed, controversially, for a pre-osteoporosis condition called osteopenia. The Fosamax patent expired in 2008 and generics have flooded the market.

The FDA announced in July that it would convene a joint meeting of advisory committees on drug safety and reproductive health to reconsider osteoporosis drugs after evidence surfaced linking long-term use with unusual breaks of the femur or thigh bone, bone death in the jaw, and possibly esophageal cancer.

This summer, the FDA has formulated the questions it will ask the panels of scientific advisers, which are often central to shaping the debate and outcome. The panels meet Friday in Adelphi, Md. The agency usually follows its advisory panels’ advice.

Biphosphonates reduce hip and spine fractures in some postmenopausal women. They include Fosamax from Merck, Boniva from Roche Therapeutics, Actonel and Atelvia from Warner Chilcott, and growing numbers of generic copies.

Worldwide sales of biphosphonates were $7.6 billion last year, down from a peak of $8.8 billion in 2007, with more than 75 percent of sales aimed at osteoporosis and the remainder at tumor-related calcium disorders, according to the data firm IMS Health. Dollar sales fell after Fosamax faced generic competition in 2008.

Ronald Rogers, a spokesman for Merck, said the company was responding to two questions from the FDA. One is whether the drugs have been proved to be safe and effective for longer term use, he said, while the other is whether to restrict that use or require “drug holidays.” Most research on the drugs is for three to five years, but many women take them indefinitely. Merck is planning to issue its report later this week, Rogers said.

His account of the questions was confirmed by a bone expert briefed on the FDA plan, who declined to be identified because the FDA is trying to keep it quiet until later this week.