FDA Panel Says to Stop Marketing Salmon Calcitonin

Experts on 2 of the US Food and Drug Administration's (FDA's) advisory panels opted to recommend that marketing of calcitonin salmon for the treatment of osteoporosis in women greater than 5 years after menopause be stopped.

The day-long joint meeting of the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee resulted in a 12 to 9 vote against continued marketing of the calcitonin nasal spray, citing lack of benefit and concerns about a possible cancer risk.

In the United States, calcitonin is marketed as Miacalcin (Novartis). It was approved in 1986 as an injection and in 1995 as a nasal spray. There is also the calcitonin salmon recombinant Fortical nasal spray (Upsher Smith Laboratories), along with some generics. The hormone increases the amount of calcium in the bones while lowering calcium levels in the blood.

In 2012, the European Medicines Agency recommended that calcitonin salmon not be used to treat osteoporosis after determining that the risk of developing cancer was 2.4% higher in patients using the nasal spray compared with in those who took placebo.

The 9 committee members who voted to keep the compound on the market insisted it had benefit, especially in a niche population such the elderly and those with acute pain from vertebral fractures.

The 12 panelists who voted to take it off thought it had very limited benefit that might be outweighed by the cancer signal that has recently begun to emerge.

Cancer Signal Weak

All of the panel members agreed that this signal was weak and that it needed further investigation.

William Cooper, MD, from Vanderbilt University School of Medicine, Nashville, Tennessee, said his vote to stop marketing calcitonin salmon was swayed by the increased risk for cancer.

"The data that were presented to us today were not really all that compelling for benefit in the broad population of people with osteoporosis, but there is a fair amount of consistency in the data on cancer. Although it appeared to be a minor increase in risk, that really tipped the scales for me," he said.

Michael Collins, MD, from the National Institutes of Health, Bethesda, Maryland, also voted to stop marketing the drug.

"The cancer question, for better or for worse, has been raised. It's on the table. That weighed against limited efficacy in the populations that have been studied. It's wishful thinking to say it could be effective in populations that haven't been studied, but there just aren't data to support this in my mind," he said.

Voting Question Too Broad

Other panel members who voted against continued marketing said they did so because the question, as posed by the FDA, which asked whether the benefit–risk assessment favored use of calcitonin salmon for the treatment of osteoporosis in women 5 years after menopause, was too broad.

"I voted no because of the way the question was worded. It was very broad, and as a clinical endocrinologist, I do see that there is a role for calcitonin in my clinical practice. However, it is a very niche population. The wording of the question is very broad, and it precluded me from being able to vote yes," said Mary D. Ruppe, MD, from the Methodist Hospital, Houston, Texas.

She added that in her opinion, the cancer risks that were presented "are inconclusive at best."

Michele J. Orza, ScD, from the Patient-Centered Outcomes Research Institute, Washington, DC, and the consumer representative on the panel, also voted to take the drug off the market.

"The wording of the question left it much too broad. Most of the discussion today was driving us toward thinking about this as a last-resort, third-line drug for a very narrow population, but this question suggested treatment of osteoporosis in women greater than 5 years [post]menopause, which to me, given the risk–benefit equation, is much too broad," she said.

Some Benefit

Panel members who voted to keep calcitonin salmon on the market felt the cancer risk was low and that the drug could benefit a subset of patients.

"I think the safety concerns are there, but further data would be helpful," said Bart Clarke, MD, from the Mayo Clinic, Rochester, Minnesota. "I think the benefit is likely weak, but we have experience with this drug clinically, and we have a whole lot of patients who can't take the other drugs. If we take this away, a lot of our patients would be in worse shape, even acknowledging the small degree of risk that we talked about."

Kenneth Burman, MD, from Washington Hospital Center, Washington, DC, recommended that use of salmon calcitonin be limited to certain subgroups and not taken off the market completely.

"The data with regard to cancer increase are intriguing and certainly need to be investigated further; however, my feelings were assuaged when I heard that the cancers were mainly basal cell carcinomas of the skin and that the increase was not statistically significant when those tumors were removed from the compilation," Dr. Burman said.

"I agree that this could be indicated in patients with certain diseases, such as renal failure [and] blood clots and in elderly women or other people who are unable to take the other medications for osteoporosis that are available," he said.

"As a practising clinician, there definitely are subpopulations for whom this drug is of benefit," said Richard Bockman, MD, from the Hospital for Special Surgery, New York City.

"In my own particular circumstance, these are patients with recent fractures who are basically treatment-naive, in whom we have a definite feeling that current therapies such as bisphosphonates actually would interfere with healing. We like to see healing go forward, and calcitonin does not, in our hands, show any evidence for blocking healing," Dr. Bockman said.

"I also think that the cancer signal is weak at this point and definitely deserves attention, and probably merits a significant warning in the use of this medication," he added.

FDA advisory panel members are vetted for conflicts of interest and waivers are granted if necessary. No waivers were granted for this meeting.