Monkeys developed tooth and jaw abscesses and two died of protozoal infections.
Human subjects developed cervical, ovarian, pancreatic, gastric and thyroid cancers and breast cancer "was the most common adverse event that led to discontinuation" in trials. Adverse effect?
Ten people were hospitalized with the skin infection cellulitis during trials and one died.
But the FDA approved Amgen's Prolia (denosumab) this month to prevent fractures in women with osteoporosis, two months earlier than expected. And with Amgen consultants sitting unabashedly on the Advisory Committee for Reproductive Health Drugs.
Prolia is not your grandmother's bone prep. Unlike old fashioned "small molecules" made from chemicals, it is a "monoclonal antibody" derived from genetically engineered Chinese hamster ovary cells that inhibits a protein, RANKL, which causes bone loss.
Twenty-seven similar monoclonal antibody products (MoAbs), which treat serious conditions like cancer and autoimmune disease, have been approved by the FDA. Twenty have Black Box Warnings because of their side effects like opportunistic infections which occur when the immune system is oppressed, anaphylaxis and malignancies.
Already, Thousand Oaks, CA-based Amgen has deployed 1,000 reps across its "bone health, inflammation and hospital teams" to call on a "large number of physicians including specialists and primary care physicians who treat postmenopausal osteoporosis," says Medical Marketing and Media. Follow the tote bags.
Like other MoAbs, Prolia denosumab "has the potential to affect multiple layers of the immune system" admits the FDA -- "three subjects required hospitalization for pneumonia after a single dose" said FDA clinical reviewer Adrienne Rothstein, MD -- so Amgen promises to conduct extensive post marketing and pharmacovigilence. Once it markets the drug and the public starts taking/testing it.
For millions of women hurt by mass marketed hormone therapy, bone drugs like bisphosphonate Fosamax -- also approved early and whose clinical data may have been distorted to gain approval says More magazine -- seemed like de'jÃ vu all over again. In addition to intractable pain and atrial fibrillation, bisphosphonates are linked to jaw bone death (osteonecrosis) and esophageal cancer, delayed fracture healing and even causing fractures. Oops.
Nor do bisphosphonates even work says a British Medical Journal article in January which looked at 68,500 patients in the US and Europe, incorporating age, gender, fracture history, hormone therapy and bisphosphonate use data. Only Vitamin D and calcium reduced fractures -- by 50 percent in all women -- according to the article, though bisphosphonates appeared to "negate the effect" of the two supplements.
"I find no conceivable justification for prescribing bisphosphonates to any woman with osteopenia or osteoporosis," says Catherine Shanahan, MD from the Bedford Center for Medical Nutrition Family Health and Wellness at Catholic Medical Center in Bedford NH. "In fact, it appears bisphosphonates are more likely to harm than help a well-nourished woman. I do not prescribe them."
Now, with injected, biologically-derived drugs marketed for bones, risks for women have just escalated, says Robert Davidson, MD, PhD, an internist in Gladewater, TX. "This is playing with fire because the tsunami of biologicals coming at us fast and furious effectively bypass most of the natural immune defenses found in our gut. Why should anyone be willing to take these risks? Why not just take Vitamin D3 along with a readily absorbable calcium supplement?"
To sell Prolia to the FDA committee, Amgen doctors presented it as a new treatment option that solves one of "the biggest problems in our field today" --adherence.
"It turns out that about half of patients put on an oral agent for osteoporosis are not taking it at the end of one year. We therefore want to have treatments that patients will actually take," said Ethel Siris, MD, of the University Medical Center, New York Presbyterian Hospital, past president of the National Osteoporosis Foundation. "A twice yearly injection in a primary care doctor's office may offer a considerable convenience for the patient and also allows the doctor to know whether or not the patient is actually receiving that therapy."
A twice yearly injection also offers Amgen the convenience of $1650 per person per year -- times the 34 million it says is at risk -- even as bone competitor, Fosamax, goes off patent.
But Prolia is no improvement over existing drugs. In addition to the infections and malignancies Amgen doctors tried to steer around at the hearing -- "this was a four year study with 412 subjects with a mean age of 64," said David Lacey, MD to explain "three subjects in our dose finding study that died of new malignancy" -- it causes the same jaw bone death of other bone drugs say FDA and Amgen doctors.