A joint FDA advisory committee voted 9-12 on Tuesday against the continued marketing of calcitonin salmon products for preventing osteoporotic fractures, citing limited efficacy and a slight risk of cancer.

Calcitonin salmon, while beneficial to a small number of patients, has shown limited effectiveness in general in treating osteoporosis of women 5 years after menopause, members of the FDA’s advisory committees on reproductive health drugs and on drug safety and risk management said.

Combine that limited effectiveness with an increased risk of cancer that the FDA has spotted after more than 2 decades of use, and the two factors led a majority of members at the joint meeting to vote against its widespread use.

Calcitonin derived from salmon was first approved to treat osteoporosis in late 1984. While nasal spray is the most common formulation available, there are several others in development, the agency said.

The FDA said Tuesday that the drug’s safety profile has remained relatively stable since that first approval—until lately, when an increased risk of cancer was detected in trials for a new oral formulation.

Calcitonin is a naturally occurring hormone involved in the process of bone building. Calcitonin derived from salmon has become a human drug because it’s more potent and has a longer half-life.

“The potential for a cancer risk with calcitonin salmon therapy cannot be ignored,” the FDA told committee members in briefing documents released ahead of the meeting. “The majority of all calcitonin salmon trials showed an increased risk estimate.”

After the cancer risk was detected, the FDA reviewed more than 20 clinical trials involving oral and nasal-use products and found a slight, but consistent risk of cancer—including melanoma—in the calcitonin salmon study groups.

The potential cancer risk drew the attention of the FDA when it combined with a lack of efficacy. The FDA said the drug hasn’t demonstrated a reduction in the risk of reducing fractures. For example, a 5-year, double-blinded, placebo-controlled trial found calcitonin salmon reduced the risk of fracture in only one of the five treatment groups in the study.

So when the heightened risk of cancer is considered, the FDA wanted to seek the opinion of the two advisory committees about the overall use of the drug and not just for the new formulation, whose application is still pending.

Many of the 12 panelists who voted against continued use of the drug admitted it has a small place for limited use in some patients who can’t tolerate other osteoporosis drugs.

“I do see there is a role for calcitonin in my clinical practice,” Mary Ruppe, MD, program director of Methodist Hospital’s endocrinology fellowship in Houston, said following her No vote. “However, it is a very niche population.”

Nine committee members voted in favor of further use, calling the cancer signal “weak.”

“There are subpopulations for which this drug is a benefit,” said Richard Bockman, MD, PhD, head of endocrine service at the Hospital for Special Surgery in New York City. Bockman and others said the cancer signals can be addressed through a significant warning in the drug’s labeling.

The FDA admitted it is difficult to discern cancer-risk conclusions from the trials. The number of patients with cancer risk was low, and the data didn’t allow for subgroup analysis.

However, other regulators have already taken action. The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended in July that calcitonin-containing medicines should only be used for short-term treatment. Health Canada issued a statement warning of an increased risk of cancer with long-term use.

Clifford Rosen, MD, from the Maine Medical Center Research Institute in Scarborough, noted that oral calcitonin drugs are used mostly for short-term treatment, and clinical data showed a benefit in reducing fractures in the first year of use.

Advocates who spoke in favor of continued use of the drug at Tuesday’s meeting said there is no biological rationale or known mechanism of action for an increased cancer risk.

Tuesday’s panel also voted 20-1 that any calcitonin salmon products in development should include fracture efficacy data to support approval for treatment of osteoporosis.

Calcitonin salmon accounted for about 4.5% of all osteoporosis drugs prescribed in 2011, or about 1.7 million packages. However, its usage has dropped by more than half in the last decade, the FDA said.

The FDA has no formal timeline for making a decision. The agency is not bound to follow the opinion of its advisory committees but usually does.

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David Pittman