Drug Profile

Teriparatide (FORTEO) was approved by the Food and Drug Administration (FDA) in November 2002 for the treatment of osteoporosis in postmenopausal women who are at high risk for fracture and to increase bone mass in men with osteoporosis, who are also at high risk for fracture. In 2009, teriparatide was also approved for the treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture.[1]

This drug is a shortened version of the human parathyroid hormone, the hormone that is the primary regulator of calcium and phosphate metabolism in bone and kidney. Teriparatide is administered by subcutaneous (under the skin) injection daily and is approved for a maximum of two years of use.

Use in women

To approve teriparatide for use in women, the FDA studied the occurrence of new, X-ray-diagnosed fractures of the vertebrae (the bones that make up the spine), referred to as vertebral fractures. Vertebral fractures are not broken bones in the common use of the phrase; rather, they are defined as changes in the height of previously undeformed vertebrae seen on X-ray. Many such fractures are not symptomatic.

Women who were defined as being at high risk for fracture were those with at least one vertebral fracture before being treated with teriparatide.

Use in men

Teriparatide is not approved to treat osteoporosis in men, but rather to increase bone mass in those with osteoporosis who are at high risk for fracture. The definition of men at high risk for fracture is the same as for women: at least one vertebral fracture. The drug does increase bone mass in men, but there are no data available at this time showing that teriparatide reduces the risk of fracture in men. In our opinion, the FDA should not have approved this drug for use in men without evidence that it reduces their fracture risk.

Strong labeling and special conditions required for marketing

Teriparatide was approved with a number of severe conditions and restrictions on its distribution and promotion because it caused osteosarcoma, a type of bone cancer, in laboratory animals. The professional product labeling or package insert for the drug contains a black-box warning about osteosarcoma. A black-box warning is the strongest type of warning that the FDA can require on a drug’s labeling. It is extremely unusual to see a new drug marketed with a black-box warning.

The drug’s manufacturer also committed to the establishment of a postapproval safety surveillance program to evaluate whether there is an association between treatment with teriparatide and the occurrence of osteosarcoma in patients, since it was shown to cause this bone cancer in animals. Data collection for the program was to begin within 90 days after the first marketed use of teriparatide. Progress reports are to be submitted to the FDA at six months, one year and annually thereafter. The program is to last for 10 years. We have serious concerns about this program, as described in the FDA’s approval letter for teriparatide. It remains to be seen whether or not, as the program is planned, it will actually be able to detect a link between the drug and osteosarcoma (if one exists) in a timely manner.

In addition, the manufacturer agreed to restricted initial marketing of teriparatide by a limited sales force with no direct-to-consumer advertising, and restrictions on the distribution of free samples of the drug. Further, the company agreed to conduct a physician education program to emphasize that teriparatide is approved only to treat patients at high risk for osteoporotic fractures.

This is one of a limited number of drugs for which the FDA requires an FDA-approved Medication Guide to be dispensed when the prescription is filled. (By clicking here you can see the Medication Guide for this drug.) An FDA advisory committee has unanimously recommended that all prescription drugs be accompanied by such Medication Guides, but at present, less than 5 percent of drugs are. The other 95 percent of drugs are accompanied by unregulated, often dangerously incomplete information leaflets not approved by the FDA.[2]

Public Citizen’s actions

Because of our concerns about the safety of this drug in relation to its effectiveness, Public Citizen’s Health Research Group testified before the FDA’s Endocrinologic Drugs Advisory Committee on July 27, 2001, to urge that the drug not be approved.[3]

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 only three times the drug levels in humans.

Information on effectiveness

In effectiveness studies, when teriparatide given with calcium and vitamin D was compared with placebo given with calcium and vitamin D, the risk of one or more new vertebral fractures was reduced from 14 percent in women given the placebo to 5 percent in those given teriparatide. Thus, the absolute difference in the risk of a new vertebral fracture with teriparatide compared to placebo was 9.3 percent. The risk of a new vertebral fracture with teriparatide relative to the risk with placebo was 65 percent. This result was statistically significant.

Using the absolute difference in risk of a new vertebral fracture, the number of patients that need to be treated with teriparatide for a period of 19 months — the length of the effectiveness studies — to prevent one new vertebral fracture can be calculated and is 11 patients.

There is no direct comparison between teriparatide and the very popular and heavily promoted osteoporosis drug alendronate (FOSAMAX); however, a study published in the medical journal The Lancet in 1996 provides some basis for a comparison.[4] In women similar to those in the teriparatide studies, the number that needed to be treated with alendronate to prevent one new vertebral fracture after 36 months was 14. This information is only given for context; the most valid type of information would be a direct head-to-head comparison of teriparatide to alendronate, which has not been done at this time.

One direct comparison of teriparatide to alendronate is available: cost. One year of treatment with teriparatide is $8,478 while alendronate, in the form of FOSAMAX, is $1,033. This is a difference of over $7,400 for one year of treatment. Generic alendronate is even less expensive at $105 for a year’s treatment, a saving of more than $8,300 a year over the cost of teriparatide. U.S. retail prescriptions for teriparatide in 2008 were $292 million.

The following table is taken from the FDA-approved professional product labeling for teriparatide and summarizes the sites of fractures, other than vertebral fractures, in women given teriparatide versus a placebo. There were 541 women in the teriparatide group and 544 in the placebo group. The number of fractures at a particular site is given, and the percentage of the group represented by that number is reported in parentheses.

Who shouldn’t take teriparatide

There are a number of groups of patients that should not use teriparatide, primarily those with an increased baseline risk of osteosarcoma, including:

• patients with Paget’s disease of the bone
• patients with unexplained high levels of alkaline phosphatase in the blood, which may mean the presence of Paget’s disease (if you are not sure, ask your doctor)
• children or growing young adults
• patients who have had radiation therapy involving the bones

In addition, patients who have ever been diagnosed with bone cancer or other cancers that have spread (metastasized) to the bones, have a bone disease other than osteoporosis, have too much calcium in the blood (hypercalcemia), or are pregnant or nursing should not use teriparatide.

Other common adverse reactions seen with teriparatide in clinical trials include nausea, dizziness, leg cramps, and headache. Redness and swelling have also occurred at the injection site. Low blood pressure (orthostatic hypotension) that can lead to fainting has been seen with the first few doses of teriparatide. Elevations of calcium levels in both the blood and urine have also been reported.

On August 30, 2013, the FDA approved a revision to the Medication Guide accompanying teriparatide’s label. The new language warns patients that the drug presents a risk of a rare, aggressive type of bone cancer called osteosarcoma. Because of this risk, the Medication Guide now warns patients not to take teriparatide for more than a total of two years.