Reviewed by endocrinologist Dolores Shoback, MD, a professor of medicine at the University of California, San Francisco, and a spokesperson for the Endocrine Society.
The experimental osteoporosis drug abaloparatide, currently under review by the U.S. Food & Drug Administration (FDA), worked as well as the only bone-building medication currently on the US market at decreasing fracture risk in a new study led by the Colorado Center for Bone Research.1 Published August 16 in the Journal of the American Medical Association, the study2 tracked the bone mass and incidence of new fractures in 2,463 women at high risk for osteoporosis-related broken bones.
Study volunteers, from ten countries including the Brazil, China, Denmark and the U.S., all had brittle bones and a history of fractures of the spine, hip, leg or arm—putting them at high risk for another potentially devastating break. For 18 months, the women gave themselves daily injections of the new drug abaloparatide, the medication teriparatide [Forteo or parathyroid hormone (1-34)] or a placebo. After 18 months, the risk of a new vertebral (spine) fracture was 4.2% for the placebo group, 0.6% for the abaloparatide group and 0.8% for the teriparatide group—amounting to an 86% reduction in this type of debilitating fracture for women on abaloparatide and a 80% reduction for women on teriparatide compared to placebo.
For fractures in other bones (including the hip, upper arm and wrist), risk was 2.7% for the abaloparatide group, 3.3% for the teriparatide group and 4.7% for the placebo group. Both types of fractures were significantly reduced due to treatment with abaloparatide.3 Bone mineral density improved with abaloparatide compared to placebo, increasing by about 4% at the hip and 11% in the spine.
Like a never-ending bridge repair and maintenance project, bone is constantly being dissolved and rebuilt by the body. Most osteoporosis drugs work by slowing the loss of bone that happens naturally during this cycle. These include bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), zoledronic acid (Reclast) and ibandronate (Boniva)’ the biological denosumab (Prolia); and calcitonin preparations such as Fortical and Miacalcin. In contrast, teriparatide and abaloparatide are anabolic drugs based on parathyroid hormone that rebuild bone mass and microarchitecture.4
Abaloparatide is a synthetic engineered version of a naturally occurring hormone in the same family as parathyroid hormone called hPTHrP (human parathyroid hormone-related protein), with the addition of amino acids to optimize its actions. PTHrP was originally discovered by researchers studying high calcium levels in the blood of some cancer patients. According to the drug’s developer Radius, based in Waltham, MA, the designer peptide based on PTHrP is involved in regulating bone formation.5
"The landmark ACTIVE trial results are important and further validate abaloparatide's potential to consistently, substantially and rapidly reduce both new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis," said Paul Miller, MD, Medical Director at the Colorado Center for Bone Research and lead author of the paper, in a prepared statement.6 "Approximately two million osteoporotic fractures occur annually in the U.S., which create physical and psychological burdens for affected women by diminishing their independence and quality of life. There is a great unmet medical need for therapies which could provide more consistent potent and early benefits to patients."
While the new drug seemed to reduce fracture risk more than teriparatide, the researchers say the study was not large enough to detect a significant difference. (That would require testing the drugs in 44,000 people, they note.) Abaloparatide seemed to increase bone mineral density faster, with bigger gains at six months. It also seemed to increase bone mineral density more than teriparatide at the hip and didn’t raise blood levels of calcium (a condition called hypercalcemia, which can tax the kidneys and limit the safety of a medication) as much. Women in both drug groups had adverse side effects like nausea, dizziness and heart palpitations; more study volunteers (81) withdrew from the abaloparatide group than the teriparatide group (50) due to side effects.7
If abaloparatide wins FDA approval, a more pressing question may be cost. Currently, the retail price for a four-week supply of teriparatide is about $2,700.8 “It can be extremely expensive for our patients even with insurance coverage,” says endocrinologist Dolores Shoback, MD, a professor of medicine at the University of California, San Francisco, and a spokesperson for the Endocrine Society. “Getting coverage can be complicated and time-consuming. You need prior authorization and often have to try a less-expensive osteoporosis drug first for a trial period, such as a bisphosphonate, and demonstrate intolerance or failure to improve bone mass.”
Abaloparatide may be more convenient because the prefilled injection pens do not need refrigeration, as teriparatide pens do, Dr. Shoback notes. Radius is also investigating a form of abaloparatide that would be delivered through a skin patch.9
The bigger issue: Getting treatments to people at high risk for bone fractures – even if they’ve had one break already. According to the National Osteoporosis Foundation, about eight million women and two million men have the disease; another 43 million are at risk. Fractures can change, or end, lives. Of the 300,000 people have an osteoporosis-related hip fractures each year in the U.S, one in four end up in a nursing home. Among those over age 50, 26% die within a year.10 Yet just 29% of women who’ve had a broken hip are using an osteoporosis drug a year later, according to an editorial co-authored by Dr. Shoback that accompanied the study. 11
Getting plenty of calcium and vitamin D, along with bone-building exercise (such as weight-bearing moves like brisk walking and strength-training routines that tug on bone), can help preserve bone density and cut risk for a break, Dr. Shoback says. Quitting smoking is also important. But many people shy away from bone medications for reasons beyond the price tag. Inexpensive bisphosphonates slow bone loss, but many people skip them due to out-sized fears about rare side effects like erosion of the jaw bone or breaks in thigh bones.
Equally important: Bone-density testing starting at age 65, earlier if you have a family history of osteoporosis or a personal history of risks like early menopause or smoking. Two-thirds of spine fractures cause no symptoms, and are discovered only during these tests, the editorial notes.12 “If you do have a fracture, a bone density test and a discussion of treatment is vital,” she says. “We’re losing ground there. People who were receiving treatment ten years ago might not even be having the discussion with their doctor today.”
The National Osteoporosis Foundation (NOF) did not comment directly on the study, but NOF President Kenneth Saag, MD, commented that, “NOF awaits direction and guidance from the FDA in regard to abaloparatide and other medications in the pipeline. NOF encourages and supports scientific advancements in the treatment of osteoporosis so as to bring an end to suffering from this debilitating condition. On behalf of patients with osteoporosis and fractures, NOF welcomes new treatment options for patients in order to reduce the risk of fractures, which can be life-altering events.”13
1. Radius: Radius Announces FDA Acceptance for Filing of New Drug Application for Abaloparatide-SC for the Treatment of Postmenopausal Women with Osteoporosis. http://investors.radiuspharm.com/releasedetail.cfm?releaseid=973511. Accessed August 22, 2016.
2. Miller PD et al, Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA, August 2016. http://jama.jamanetwork.com/article.aspx?articleid=2544640. Accessed August 25. 2016.
3. Miller, Table 2.
4. National Osteoporosis Foundation: Medicines Approved to Prevent and/or Treat Osteoporosis. Accessed August 22, 2016
5. Radius: Investigational drug product candidate Abaloparatide-SC. http://www.radiuspharm.com/r-d/pipeline.html. Accessed August 22, 2016.
6. Radius: JAMA Publishes Positive Phase 3 Data for Abaloparatide in Postmenopausal Women With Osteoporosis. http://investors.radiuspharm.com/releasedetail.cfm?releaseid=984545. Accessed August 22, 2016.
7. Miller, table 3.
8. Forteo retail price as of August 22, 2016. https://www.drugs.com/price-guide/forteo.
9. Radius: Investigational drug product candidate Abaloparatide-SC. http://www.radiuspharm.com/r-d/pipeline.html
10. National Osteoporosis Foundation: Osteoporosis Fast Facts. http://www.nof.org/wp-content/uploads/2015/12/Osteoporosis-Fast-Facts.pdf. Accessed August 22, 2016.
11. Cappola and Shoback: Osteoporosis Therapy in Postmenopausal Women With High Risk of Fracture. JAMA August 16, 2016 Volume 316, Number 7. http://jama.jamanetwork.com/article.aspx?articleid=2544620. Accessed August 25, 2016.
12. Cappola and Shoback: Osteoporosis Therapy in Postmenopausal Women With High Risk of Fracture. JAMA August 16, 2016 Volume 316, Number 7
13. Comment from Dr. Saag came from NOF Press Office, Clair Gill, Sr. Director, Consumer & Corporate Outreach, Chief Marketing Officer. National Osteoporosis Foundation. Arlington, VA 22202.