FDA Approves Abaloparatide to Treat Men with Osteoporosis & a High Risk of Fracture

On Dec. 19, 2022, the U.S. Food & Drug Administration (FDA) approved subcutaneous abaloparatide (Tymlos) for the treatment of men with osteoporosis at high risk of fracture, as well as adult patients for whom other osteoporosis therapies have proved ineffective or can’t tolerate other therapies.¹

The FDA had previously approved abaloparatide for the treatment of postmenopausal women with osteoporosis at high risk of fracture.²

Abaloparatide is an analog of parathyroid hormone-related peptide [PTHrP(1-34)].³ High fracture risk is defined as a history of osteoporotic fracture or multiple risk factors for fracture, such as age, low bone mineral density (BMD) and previous fragility fracture.⁴

This latest FDA approval was based on findings of a 12-month, safety and efficacy study of subcutaneous abaloparatide in men with osteoporosis (ATOM; NCT03512262).⁵ The multicenter, phase 3 study was randomized and double-blinded.

In the study, researchers evaluated 80 μg of abaloparatide given daily as a subcutaneous injection to men with osteoporosis (n=149) aged 40–85 years old. This group was compared with a group of men with osteoporosis who received placebo injections (n=79). All patients also took daily supplemental calcium (500–1,000 mg) and vitamin D (400–800 IU).

The study’s primary outcome measure was the change in percentage from baseline in BMD of the lumbar spine at month 12. Secondary outcome measures were the change in percentage from baseline in BMD of the total hip and femoral neck at month 12, the change in percentage from baseline in BMD of the lumbar spine at month six and treatment-associated emergent adverse events associated with hypercalcemia within 13 months.

Results

Most men in the study were white (approximately 95%); 4% were Asian, and 0.4% were Black. Another 16% of study patients identified as Hispanic. At baseline, mean T-scores at the lumbar spine and femoral neck were -2.1, and mean T-scores at the total hip were -1.7.

At month 12, treatment with abaloparatide had led to significant increases in BMD at the lumbar spine, total hip and femoral neck (P<0.0001), compared with placebo. For the primary efficacy measure of the lumbar spine, the change in percentage in BMD from baseline was 8.5% for patients treated with abaloparatide and 1.2% for patients who received the placebo—a 7.3% treatment difference (99% confidence interval [CI] 5.1%, 9.6%; P<0.0001). No differences in the effect of abaloparatide were seen across subgroups defined by ethnicity, race, age, geographic region, BMD at baseline or the presence or absence of prior fracture.

During the trial, none of the patients had an adverse reaction with a fatal outcome. Serious adverse reactions were reported by 5.4% of patients who received abaloparatide and 5.1% of patients who received placebo. Adverse reactions that led to patients discontinuing treatment were reported in 6.7% of patients who received abaloparatide and 5.1% of patients who received placebo.

Dizziness was the most common adverse reaction (2%) that led to the discontinuation of the study drug in patients who received abaloparatide. Hypercalcemia occurred in 3% of patients who received abaloparatide and none of the patients who received placebo. The pre-dose serum calcium level was similar to baseline in both groups. More patients treated with abaloparatide who had mild or moderate renal impairment (4%) developed hypercalcemia than those with normal renal function (0%). Overall, the other most common adverse reactions (incidence ≥2%) were injection-site reactions (i.e., 13% erythema, 7% swelling and/or 6% pain), abdominal distension (3%), abdominal pain (3%), arthralgia (7%), bone pain (2%), bruising (3%), diarrhea (3%) and nausea (3%).

Osteoporosis treatments for men are as important as they are for women because a large percentage of men over the age of 50 years will have an osteoporotic-related fracture. Men generally have higher rates of fracture-related mortality.

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Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. News release: Radius Health’s Tymlos (abaloparatide) receives U.S. FDA approval as a treatment to increase bone density in men with osteoporosis at high risk for fracture. 2022 Dec 20.
2. New drug application approval letter: Tymlos (abaloparatide) injection. 2017 April 28.
3. Highlights of prescribing information: Tymlos (abaloparatide) injection for subcutaneous use. U.S. Food & Drug Administration. 19 Dec 2022.
4. Patients at high risk of fracture. International Osteoporosis Foundation. 2023.
5. Radius Health Inc. Safety and efficacy of abaloparatide-sc in men with osteoporosis (ATOM; NCT03512262). ClinicalTrials.gov. 2021 Nov 8.