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

CAMBRIDGE, MA, USA I December 20, 2022 I Radius Health, Inc. ("Radius" or the "Company") today announced that the U.S. Food and Drug Administration (FDA) has approved TYMLOS® (abaloparatide), a parathyroid hormone related peptide [PTHrP(1‑34)] analog, as a treatment to increase bone density in men with osteoporosis at high risk of fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or in patients who have failed or are intolerant to other available osteoporosis therapy.1 This approval is based on the Phase 3 ATOM study ("Abaloparatide Treatment of Men; BA058-05-019"), which was a randomized, double-blind, placebo-controlled, 12-month multicenter study designed to evaluate the efficacy and safety of abaloparatide 80 micrograms in men with osteoporosis.1 The primary efficacy endpoint of the ATOM study was the percent change from baseline in bone mineral density (BMD) at the lumbar spine at 12 months, which was 8.5% and 1.2% in abaloparatide and placebo groups, respectively.1 This treatment difference between abaloparatide and placebo was 7.3% (99% CI: 5.1%, 9.6%; p<0.0001).1

Osteoporosis-related fractures are an important health concern because of related morbidity, mortality, and cost.2 Bruce Mitlak, M.D., the Chief Medical Officer of Radius, emphasized that "30% of all hip fractures occur in men and approximately 25% of men over the age of 50 years will sustain an osteoporotic-related fracture. Additionally, while the overall prevalence of fragility fractures is higher in women, men generally have higher rates of fracture-related mortality."2,3,4

"TYMLOS has been helping postmenopausal women with osteoporosis at high risk for fracture for over five years. We are excited that with this approval, we can bring TYMLOS to a new population," said Chhaya Shah, Chief Business Officer at Radius.1 "We are grateful to the men who participated in the ATOM study, as they played a pivotal role in helping bring this important treatment to men with osteoporosis at high risk of fracture."

TYMLOS was approved in April 2017 for the treatment of postmenopausal women with osteoporosis at high risk for fracture, based on the Phase 3 ACTIVE study.1 Abaloparatide met the primary efficacy endpoint with a statistically significant relative risk reduction of new vertebral fracture at Month 18 versus placebo (0.6% versus 4.2%, respectively, p<0.0001).1 There was an 86% relative risk reduction in new vertebral fractures in postmenopausal women receiving abaloparatide versus placebo.1

The most common adverse reactions (incidence ≥2%) reported with TYMLOS in men with osteoporosis are injection site erythema (13%), dizziness (9%), arthralgia (7%), injection site swelling (7%), injection site pain (6%), contusion (3%), abdominal distention (3%), diarrhea (3%), nausea (3%), abdominal pain (2%), and bone pain (2%).1 The most common adverse reactions (incidence ≥2%) reported with TYMLOS in postmenopausal women with osteoporosis are hypercalciuria (11%), dizziness (10%), nausea (8%), headache (8%), palpitations (5%), fatigue (3%), upper abdominal pain (3%), and vertigo (2%).1  Please see the detailed Important Safety Information provided below for more important safety information.

"Radius stands behind our commitment to the bone health community and with this approval, men with osteoporosis at high risk for fracture will have an additional important treatment option," said Scott Briggs, Chief Executive Officer at Radius.

IMPORTANT SAFETY INFORMATION1

Contraindications: TYMLOS is contraindicated in patients with a history of systemic hypersensitivity to abaloparatide or to any component of the product formulation. Reactions have included anaphylaxis, dyspnea, and urticaria.

Risk of Osteosarcoma: It is unknown whether TYMLOS will cause osteosarcoma in humans. Osteosarcoma has been reported in patients treated with a PTH-analog in the post marketing setting; however, an increased risk of osteosarcoma has not been observed in observational studies in humans. There are limited data assessing the risk of osteosarcoma beyond 2 years of TYMLOS use. Avoid use of TYMLOS for patients at an increased baseline risk for osteosarcoma including patients with open epiphysis (pediatric and young adult patients); metabolic bone diseases other than osteoporosis, including Paget's disease of the bone; bone metastases or a history of skeletal malignancies; prior external beam or implant radiation therapy involving the skeleton; or hereditary disorders predisposing to osteosarcoma.

Orthostatic Hypotension: Orthostatic hypotension may occur with TYMLOS, typically within 4 hours of injection. Associated symptoms may include dizziness, palpitations, tachycardia, or nausea, and may resolve by having the patient lie down. For the first several doses, TYMLOS should be administered where the patient can sit or lie down if necessary.

Hypercalcemia: TYMLOS may cause hypercalcemia. TYMLOS is not recommended in patients with pre-existing hypercalcemia or in patients who have an underlying hypercalcemic disorder, such as primary hyperparathyroidism, because of the possibility of exacerbating hypercalcemia.

Hypercalciuria and Urolithiasis: TYMLOS may cause hypercalciuria. It is unknown whether TYMLOS may exacerbate urolithiasis in patients with active or a history of urolithiasis. If active urolithiasis or pre-existing hypercalciuria is suspected, measurement of urinary calcium excretion should be considered.

Pregnancy and Lactation: TYMLOS is not indicated for use in females of reproductive potential.

Adverse Reactions: 

  • The most common adverse reactions (incidence ≥2%) reported with TYMLOS in postmenopausal women with osteoporosis are hypercalciuria (11%), dizziness (10%), nausea (8%), headache (8%), palpitations (5%), fatigue (3%), upper abdominal pain (3%), and vertigo (2%).
  • The most common adverse reactions (incidence ≥2%) reported with TYMLOS in men with osteoporosis are injection site erythema (13%), dizziness (9%), arthralgia (7%), injection site swelling (7%), injection site pain (6%), contusion (3%), abdominal distention (3%), diarrhea (3%), nausea (3%), abdominal pain (2%), and bone pain (2%).

Please see full Prescribing Information.

About Abaloparatide1
Abaloparatide (TYMLOS®) was approved in April 2017 by the U.S. Food and Drug Administration for the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture), or patients who have failed or are intolerant to other available osteoporosis therapy. In postmenopausal women with osteoporosis, TYMLOS reduces the risk of vertebral fractures and nonvertebral fractures. Abaloparatide is supplied as a single-patient multi-use prefilled pen designed to subcutaneously administer 80 micrograms per dose over a 30-day period.

About ATOM Phase 3 Study1
The ATOM pivotal Phase 3 study, Study BA058-05-019, was a randomized, double-blind, placebo-controlled study in 228 men with osteoporosis to assess efficacy and safety of abaloparatide injection. Subjects were randomized in a 2:1 treatment ratio to receive subcutaneous administration of either abaloparatide 80 micrograms or placebo for 12 months to determine the effect of abaloparatide on lumbar spine bone mineral density (BMD) and other bone health-related endpoints. The primary efficacy endpoint was the percent change from baseline in BMD at the lumbar spine at 12 months. Key secondary efficacy endpoints included the percent change from baseline in BMD at the total hip and femoral neck at 12 months.5

About the ACTIVE Phase 3 Study1
The ACTIVE pivotal Phase 3 fracture prevention trial (Abaloparatide Comparator Trial in Vertebral Endpoints; Study BA058-05-003) was a randomized, double-blind, placebo-controlled trial in 2,463 postmenopausal osteoporotic women randomized to receive daily doses of one of the following for 18 months: 80 ug of abaloparatide; a matching placebo; or the approved dose of 20 ug of teriparatide. Study medication was self-administered daily by subcutaneous injection for a maximum of 18 months. The primary efficacy endpoint was the number of patients treated with abaloparatide-SC with incident vertebral fractures at the end of treatment as compared to those who received placebo. The pre-specified secondary efficacy parameters included, among other endpoints, reduction in the incidence of non-vertebral fractures; changes in BMD of the spine, hip, and femoral neck from baseline to end of treatment as assessed by DXA and as compared to teriparatide; and the number of hypercalcemic events in abaloparatide-SC treated patients when compared to teriparatide at end of treatment.6

About Osteoporosis
Osteoporosis is a bone disorder that occurs with aging and is associated with reduced bone density, compromised bone strength, and impaired bone quality, resulting in an increased risk of fractures.7

About Radius
Radius is a global biopharmaceutical company focused on addressing unmet medical needs in the areas of bone health and oncology. Radius' lead product, TYMLOS® (abaloparatide) injection, was approved by the U.S. Food and Drug Administration in April 2017 for the treatment of postmenopausal women with osteoporosis at high risk for fracture, and in December 2022 for the treatment of men with osteoporosis at high risk for fracture. The Radius clinical pipeline includes the investigational drug, elacestrant (RAD1901), for potential use in the treatment of hormone-receptor positive breast cancer out-licensed to Menarini Group.

1. TYMLOS [prescribing information]. Boston, MA: Radius Health, Inc.
2. Sözen T, Özışık L, Başaran NÇ. An overview and management of osteoporosis. Eur J Rheumatol. 2017 Mar;4(1):46-56. doi: 10.5152/eurjrheum.2016.048. Epub 2016 Dec 30.
3. Willson T, Nelson S, Newbold J, LaFleur J. The clinical epidemiology of male osteoporosis: a review of recent literature. Clin Epidemiol. 2015 Jan 9.
4. Cauley JA, Cawthon PM, Peters KE, Cummings SR, Ensrud KE, Bauer DC, Taylor BC, Shikany JM, Hoffman AR, Lane NE, Kado DM, Stefanick ML, Orwoll ES. Osteoporotic Fractures in Men (MrOS) Study Research Group. Risk Factors for Hip Fracture in Older Men: The Osteoporotic Fractures in Men Study (MrOS). J Bone Miner Res. 2016 Oct.
5. Czerwinski E, Cardona J, Plebanski R, Recknor C, Vokes T, Saag KG, Binkley N, Lewiecki EM, Adachi J, Knychas D, Kendler D, Orwoll E, Chen Y, Pearman L, Li YH, Mitlak B. The Efficacy and Safety of Abaloparatide-SC in Men With Osteoporosis: A Randomized Clinical Trial. J Bone Miner Res. 2022 Oct 3.
6. Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial. JAMA. 2016;316(7):22-33 [published correction appears in JAMA. 2017;317(4):442].
7. About Osteoporosis. Osteoporosis Foundation. Available at: https://www.osteoporosis.foundation/patients/about-osteoporosis.

SOURCE: Radius Health

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