Clinical Trials

Date: 2017-09-10

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the ASBMR 2017 Annual Meeting

Company: Radius Health (USA - MA)

Product: Eladynos®/Tymlos® (abaloparatide)

Action mechanism:

• peptide. Abaloparatide-SC is a novel 34–amino acid peptide created to be a potent and selective activator of the parathyroid hormonereceptor type 1 (PTHR1) signaling pathway.

Disease: postmenopausal women with osteoporosis at high risk for fracture defined as history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy

Therapeutic area: Bone diseases

Country: Argentina, Brazil, Czech Republic, Denmark, Estonia, Hong Kong, Lithuania, Poland, Romania, USA

Trial details:

• The Phase 3 ACTIVE (Abaloparatide Comparator Trial In Vertebral Endpoints) trial was a randomized, double-blind, placebo-controlled, comparative, multicenter, 18 month international study in 2,463 postmenopausal women with osteoporosis designed to evaluate the efficacy and safety of abaloparatide-SC 80 mcg to reduce the risk of vertebral and nonvertebral fractures. (NCT01343004)
• ACTIVExtend, an extension of ACTIVE, enrolled patients who had completed 18 months of abaloparatide-SC or placebo in ACTIVE to receive up to 24 additional months of open-label alendronate.

Latest news:

• • On September 10, 2017, Radius Health presented results from the completed ACTIVExtend study in an abstract titled "Sustained Fracture Risk Reduction with Sequential Abaloparatide/Alendronate: Results of ACTIVExtend" at the ASBMR 2017 Annual Meeting in Denver, Colorado. In ACTIVExtend, patients who had completed 18 months of Tymlos® or placebo in the ACTIVE Phase 3 trial were transitioned to receive 24 additional months of open-label alendronate. Patients who received this sequential therapy demonstrated statistically significant fracture risk reductions through 3.5 years.
• At the 43-month timepoint, the previous Tymlos®-treated patients had a significant 84 percent relative risk reduction (p<0.0001) in the incidence of new vertebral fractures compared with women who received placebo followed by alendronate. Additionally, Tymlos® followed by alendronate demonstrated a 39 percent relative risk reduction in nonvertebral fractures (p=0.038), compared with women who received placebo followed by alendronate.
• • On May 24, 2017, Radius Health announced positive results from the completed 24 month ACTIVExtend trial, which met all of its primary and secondary endpoints. In ACTIVExtend, patients who had completed 18 months of Tymlos® (abaloparatide) injections or placebo in the ACTIVE Phase 3 trial were transitioned to receive 24 additional months of open-label alendronate.
• At the 43 month timepoint, the previous Tymlos®-treated patients had a significant 84% relative risk reduction in the incidence of new vertebral fractures compared with women who received placebo followed by alendronate. They also demonstrated a 39% risk reduction in nonvertebral fractures, a 34% risk reduction clinical fractures and a 50% risk reduction in major osteoporotic fractures compared with women who received placebo followed by alendronate.
• The adverse events reported during the alendronate treatment period were similar between the previous Tymlos®-treated patients and the previous placebo group. The incidences of cardiovascular adverse events including serious adverse events were similar between groups. There have been no cases of osteonecrosis of the jaw (ONJ) or atypical femoral fracture (AFF) in the entire Tymlos® development program.
• • On September 18, 2016, Radius Health announced that additional positive results from the Phase 3 ACTIVE  trial were published in the Journal of Bone and Mineral Research (JBMR).  In the article "Effects of Abaloparatide-SC on Fracture and Bone Mineral Density in Subgroups of Postmenopausal Women with Osteoporosis and Varying Baseline Risk Factors", patients in the ACTIVE trial were stratified into prespecified subgroups of baseline risk factors, inclusive of Bone Mineral Density, prior fracture history and age, to determine the consistency of the response for abaloparatide-SC versus placebo. Abaloparatide-SC increased bone mineral density (BMD) 3.4% at the total hip, 2.9% at the femoral neck, and 9.2% at the lumbar spine at 18 months.
• • On August 16, 2016,  Radius Health announced that results from the Phase 3 ACTIVE (Abaloparatide Comparator  Trial In Vertebral Endpoints) trial were published in the Journal of the American Medical Association (JAMA). This landmark trial enrolled 2,463 patients to evaluate the safety and efficacy of investigational drug abaloparatide for the treatment of postmenopausal women with osteoporosis.  The ACTIVE results showed that patients treated with daily abaloparatide for 18 months had a significantly greater reduction in the incidence of new vertebral fractures (p < 0.001) and nonvertebral fractures (p = 0.049) compared to placebo.

Is general: Yes