FDA Approves Newest Osteoporosis Drug

On April 28, 2017, the FDA approved another drug to treat osteoporosis in postmenopausal women at high risk of fracture or those who have failed other therapies.

The drug, Radius Health Inc.’s Tymlos, is given by injection. In clinical trials, the drug was shown to reduce the absolute risk of spine fractures by 3.6% compared with a placebo and to reduce the risk of non-spinal fractures by 2%.

Tymlos carries a boxed warning of the risk of bone cancer similar to one for Forteo, a drug made by Eli Lilly & Co. Tymlos is also expected to compete with Amgen Inc.’s Prolia.

The company said the FDA’s approval was based on results at 18 months from the landmark ACTIVE trial and first six months of ACTIVExtend trial that demonstrated “consistent significant and rapid reductions in the risk of vertebral and nonvertebral fractures regardless of age, years since menopause, presence or absence of prior fracture (vertebral or nonvertebral) and bone mineral density (BMD) at baseline.”

In human clinical studies, the company says the drug has been shown to “decrease the incidence of new vertebral and nonvertebral fractures, to increase bone mineral density (BMD), and to increase a marker of bone formation.” In addition, the anabolic effect of the drug was “demonstrated in animal studies by increases in BMD and bone mineral content that correlated with increases in bone strength at vertebral and/or nonvertebral sites.”

The results from the ACTIVE trial were published in the Journal of the American Medical Association in August 2016, and the results of the first six months of ACTIVExtend were published in the Mayo Clinic Proceedings in February 2017.

Human Parathyroid Hormone

According to the company, Tymlos is a human parathyroid hormone related peptide PTHrP analog indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture defined as a history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, the drug reduces the risk of vertebral fractures and nonvertebral fractures

Doses, Warnings and Adverse Reactions

Recommended dose is 80 mcg subcutaneously once daily; patients should receive supplemental calcium and vitamin D if dietary intake is inadequate. The drug is administered as a subcutaneous injection into periumbilical region of abdomen.

There are no contraindications noted, but there are warning and precautions.

• Orthostatic Hypotension: Instruct patients to sit or lie down if symptoms develop after dose administration.
• Hypercalcemia: Avoid use in patients with pre-existing hypercalcemia and those known to have an underlying hypercalcemic disorder, such as primary hyperparathyroidism.
• Hypercalciuria and Urolithiasis: Monitor urine calcium if preexisting hypercalciuria or active urolithiasis are suspected.

The most common adverse reactions (incidence ≥2%) are hypercalciuria, dizziness, nausea, headache, palpitations, fatigue, upper abdominal pain and vertigo.

Jefferies analyst Eun Yan wrote in a research note, “While FDA approval is positive, we continue to see significant commercial hurdles as likely given competition.” He estimated the drug will generate peak annual sales of $450 million by 2028.