Public Citizen issues warning against Forteo

OB/GYN News, May 15, 2003 by Kate Johnson

An alert issued by the consumer watchdog group Public Citizen warns consumers to avoid using the osteoporosis drug teriparatide, because studies in rats have linked it to an increased risk of bone cancer.

But the drug's manufacturer, Eli Lilly, has countered that teriparatide (Forteo) has been used in more than 2,000 people in clinical trials, and not one case of osteosarcoma has been reported. And according to a Canadian bone mineral specialist interviewed for this article, bone growth in rats is fundamentally different from that in humans, so the animal data should not be extrapolated to patients who are using the drug.

Last month, the Washington-based Public Citizen issued a "do not use" alert for teriparatide, warning that the drug, which was approved by the Food and Drug Administration last November, may cause osteosarcoma.

"Teriparatide has led to bone cancer in laboratory animals, a risk that far outweighs the drug's benefit," the group wrote in a press release.

In its most recent monthly newsletter, "Worst Pills Best Pills," the group says it voiced its concerns to the FDA's Endocrinologic and Metabolic Drugs Advisory Committee in 2001.

"We testified that the ability of teriparatide to cause cancer--in this case osteosarcoma--in rats was some of the most striking animal carcinogenicity data we had ever seen. Tumors developed in the animals at even the lowest dose level of teriparatide administered, which was 1.6 times the dose intended for humans," according to the newsletter article.

"We would like to see individuals avoid this drug until there's evidence that it doesn't cause osteosarcoma," Public Citizen spokesperson Larry Sasich, Pharm.D., said in an interview.

"We would like to see a mandatory registry where patients who are using this drug are followed over time. And we can see no reason why this safety issue could not have been answered before the drug was marketed. There was no rush. There are other osteoporosis treatments," he said.

Debbie Davis, a spokesperson for Eli Lilly of Indianapolis, said the FDA approved Forteo under several conditions, and the company is conducting a postapproval osteosarcoma surveillance study.

Public Citizen "stated their position at the FDA advisory committee, but the FDA chose to approve the drug anyway," she said in an interview, adding that Forteo is the first approved osteoporosis treatment that stimulates new bone formation. In contrast, other available therapies prevent bone loss.

"Overall their criticism doesn't square with the extensive clinical trials and the FDA's comprehensive review before it approved Forteo for its safety and efficacy. More than 2,000 people have participated in Forteo clinical trials, and none have developed osteosarcoma," she added.

But Dr. Sasich said the absence of human osteosarcoma cases in a small number of patients over a short period of time is not proof of the drug's safety.

Furthermore, the fact that the FDA required a black box warning (see box) in the package insert and stipulated that patient medication guides be included in both new and refill prescriptions speaks to the product's potential risk, he said.

"This is one of the few drugs that has come on the market with a black box warning, which is very unusual. It's the strongest type of warning that the FDA can require for a drug. And only a handful of drugs require medication guides, so that gives you a good idea of the FDA's concerns," Dr. Sasich said.

Dr. Gustavo Duque, a bone mineral specialist at McGill University in Montreal, said data on osteosarcomas in rats should not be extrapolated to humans.

"This is a clear misunderstanding of a side effect found in rats," he said. "Rats have a very different bone structure than humans."

Dr. Duque, who said he has no financial ties to Eli Lilly or its competitors, says all vertebrates have a cartilaginous structure known as a growth plate that is situated in distal and proximal segments of long bones. This growth plate is the source of growth in bones. In humans, the growth plate produces bone until the teen years and then is closed and mineralized; in rats the growth plate stays active throughout their lives.

"This means that in rats the growth plate may become a source of cartilage related neoplasm, which happened in the mentioned studies. We cannot extrapolate this to humans," said Dr. Duque, a geriatrician and researcher in the field of aging bone and senile osteoporosis at the division of geriatric medicine, McGill University, and the Bloomfield Center for Research in Aging in Montreal.

The FDA approved teriparatide for the treatment of osteoporosis in postmenopausal women who are at high risk for having a fracture. The drug is also approved to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture.

RELATED ARTICLE: Teriparatide's Black Box Warning

"In male and female rats, teriparatide caused an increase in the incidence of osteosarcoma (a malignant bone tumor) that was dependent on dose and treatment duration. The effect was observed at systemic exposures to teriparatide ranging from 3 to 60 times the exposure in humans given a 20-[micro]g dose. Because of the uncertain relevance of the rat osteosarcoma finding to humans, teriparatide should be prescribed only to patients for whom the potential benefits are considered to outweigh the potential risk. Teriparatide should not be prescribed for patients who are at increased baseline risk for osteosarcoma (including those with Paget's disease of bone or unexplained elevations of alkaline phosphatase, open epiphyses [open bone plates], or prior radiation therapy involving the skeleton)."