The anabolic osteoporosis treatment abaloparatide (Tymlos, Radius Health) works in men as well as women, new data indicate.
Findings from the Abaloparatide for the Treatment of Men With Osteoporosis (ATOM) randomized, double-blind, placebo-controlled, phase 3 study were presented last week at the American Association of Clinical Endocrinology (AACE) Annual Meeting 2022.
Abaloparatide, a subcutaneously administered parathyroid-hormone–related protein (PTHrP) analog, resulted in significant increases in bone mineral density by 12 months at the lumbar spine, total hip, and femoral neck compared with placebo in men with osteoporosis, with no significant adverse effects.
"Osteoporosis is underdiagnosed in men. Abaloparatide is another option for an ignored population," presenter Neil Binkley, MD, of the University of Wisconsin School of Medicine and Public Health Madison, told Medscape Medical News.
Abaloparatide was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of postmenopausal women at high risk for fracture due to a history of osteoporotic fracture or multiple fracture risk factors, or who haven't responded to or are intolerant of other osteoporosis therapies.
While postmenopausal women have mainly been the focus in osteoporosis, men account for approximately 30% of the societal burden of osteoporosis and have greater fracture-related morbidity and mortality than women.
About one in four men over the age of 50 years will have a fragility fracture in their lifetime. Yet, they're far less likely to be diagnosed or to be included in osteoporosis treatment trials, Binkley noted.
Asked to comment, session moderator Thanh D. Hoang, DO, told Medscape Medical News, "I think it's a great option to treat osteoporosis, and now we have evidence for treating osteoporosis in men. Mostly the data have come from postmenopausal women."
Screen Men With Hypogonadism or Those Taking Steroids
"This new medication is an addition to the very limited number of treatments that we have when patients don't respond to [initial] medications. To have another anabolic bone-forming medication is very very good," said Hoang, who is professor and program director of the Endocrinology Fellowship Program at Walter Reed National Military Medical Center, Bethesda, Maryland.
Radius Health filed a Supplemental New Drug Application with the FDA for abaloparatide (Tymlos) subcutaneous injection in men with osteoporosis at high risk for fracture in February. There is a 10-month review period.
Binkley advises bone screening for men who have conditions such as hypogonadism or who are taking glucocorticoids or chemotherapeutics.
But, he added, "I think that if we did nothing else good in the osteoporosis field, if we treated people after they fractured that would be a huge step forward. Even with a normal T score, when those people fracture, they [often] don't have normal bone mineral density...That's a group of people we're ignoring still. They're not getting diagnosed and they're not getting treated."
ATOM Study: Significant BMD Increases at Key Sites
The approval of abaloparatide in women was based on the phase 3, 18-week ACTIVE trial of more than 2000 high-risk women, in whom abaloparatide was associated with an 86% reduction in vertebral fracture incidence compared with placebo, and also significantly greater reductions in nonvertebral fractures compared with both placebo and teriparatide (Forteo, Eli Lilly).
The ATOM study involved a total of 228 men aged 40-85 years with primary or hypogonadism-associated osteoporosis randomized 2:1 to receive subcutaneous 80 μg abaloparatide or injected placebo daily for 12 months. All had T-scores (based on male reference range) of ≤ −2.5 at the lumbar spine or hip, or ≤ −1.5 and with radiologic vertebral fracture or a history of low trauma nonvertebral fracture in the past 5 years, or T-score ≤ −2.0 if older than 65 years.
Increases in bone mineral density from baseline were significantly greater with abaloparatide compared with placebo at the lumbar spine, total hip, and femoral neck at 3, 6, and 12 months. Mean percentage changes at 12 months were 8.5%, 2.1%, and 3.0%, for the three locations, respectively, compared with 1.2%, 0.01%, and 0.2% for placebo (all P ≤ .0001).
Three fractures occurred in those receiving placebo and one with abaloparatide.
For markers of bone turnover, median serum procollagen type I N-terminal propeptide (s-PINP) was 111.2 ng/mL after 1 month of abaloparatide treatment and 85.7 ng/mL at month 12. Median serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX) was 0.48 ng/mL at month 6 and 0.45 ng/mL at month 12 in the abaloparatide group. Geometric mean relative to baseline s-PINP and s-CTX increased significantly at months 3, 6, and 12 (all P < .001 for relative treatment effect of abaloparatide vs placebo).
The most commonly reported treatment-emergent adverse events were injection site erythema (12.8% vs 5.1%), nasopharyngitis (8.7% vs 7.6%), dizziness (8.7% vs 1.3%), and arthralgia (6.7% vs 1.3%), with abaloparatide vs placebo. Serious treatment-emergent adverse event rates were similar in both groups (5.4% vs 5.1%). There was one death in the abaloparatide group, which was deemed unrelated to the drug.
Binkley has reported receiving consulting fees from Amgen and research support from Radius. Hoang has reported disclosures with Acella Pharmaceuticals and Horizon Therapeutics (no financial compensation).
AACE 2022 Annual Meeting. Presented May 12, 2022.
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.