Data in NEJM show Novartis drug Aclasta® significantly reduced the risk of fracture in men with osteoporosis with once-yearly infusion
· In this first and only study in male osteoporosis to use fractures as the primary endpoint, Aclasta demonstrated a fracture risk reduction of 67% versus placebo1
· Osteoporosis in men is often underdiagnosed and undertreated2, yet among people over 50, approximately 40% of all osteoporotic fractures occur in men3
· New findings add to strong body of data confirming existing safety and efficacy profile of Aclasta4,5,6,7,8, approved since 2008 for osteoporosis treatment in men
Novartis has announced that the New England Journal of Medicine (NEJM) published results from a study which found that once-yearly Aclasta® (zoledronic acid 5 mg) significantly reduced the risk of spine fractures by 67% versus placebo over two years in men with osteoporosis (p=0.002). This is the first and only study in men with osteoporosis to use fractures as the primary endpoint.
“These data now published in the NEJM provide convincing evidence that Aclasta significantly reduced fracture risk in men with osteoporosis,” said Professor Steven Boonen, University of Leuven, Belgium and lead author of the study publication. “The development of recommendations for detecting and treating osteoporosis in men has been limited until now by the lack of unambiguous evidence of effective anti-fracture therapies in men. This study should have positive implications for the treatment of male patients with osteoporosis and should pave the way for improvements in care.”
The study also showed that Aclasta reduced the risk of one or more new moderate-to-severe spine fractures by 81% at month 12 (p=0.01) and 63% at month 24 (p=0.03) compared with the placebo group1. In addition, Aclasta produced significant and sustained improvements in bone mineral density at the spine and hip bones (lumbar spine, total hip and femoral neck bone (p=<0.05 for all comparisons) and reduced the risk of height loss (-2.2 mm and -4.5 mm at month 24 for Aclasta and placebo (p=0.002), respectively).
"These data reinforce once-yearly Aclasta as highly effective at protecting patients against fracture, over a two-year period," said Lutz Hegemann, Global Head of Development, Established Medicines, Novartis Pharma. "The identification and treatment of men with osteoporosis at risk of fractures with Aclasta may reduce the substantial morbidity, mortality and the public health costs that result from osteoporotic fractures.”
Aclasta was approved in 2008 for the treatment of osteoporosis in men, and is now approved for up to six indications to treat a broad spectrum of patients, from the newly diagnosed to those with more severe forms of osteoporosis.
About the study
The male osteoporosis fracture study was a 24-month, randomized, placebo-controlled, parallel-group study. The study was conducted at approximately 150 centers in Europe, South America, Africa and Australia, with a total of 1,199 men (aged 50-85 years) with primary osteoporosis or osteoporosis associated with low serum testosterone levels. Inclusion criteria considered baseline bone mineral density and/or the presence of one to three prevalent vertebral fractures. Patients received Aclasta or placebo as an annual 15-30 minute intravenous infusion at baseline and 12 months. Patients also received daily calcium 1,000-1,500 mg and vitamin D 800-1200 IU.
The primary endpoint was the proportion of patients with one or more new morphometric vertebral fractures over 24 months. Secondary endpoints included percentage changes in lumbar spine, total hip and femoral neck bone mineral density, change in height and the proportion of one or more new moderate-to-severe, or new or worsening vertebral fracture over 12 and 24 months. Overall safety of Aclasta versus placebo was also assessed as a secondary objective.
Over two years, 1.6% of patients, (9 patients out of 553) randomized to the Aclasta group experienced one or more new morphometric vertebral fractures, or fractures of the spine, diagnosed by X-ray, compared with 4.9% of patients (28 patients out of 557) randomized to the placebo group. This represents a statistical significant fracture reduction of 67% in the Aclasta group (p=0.002). Total testosterone status did not affect the anti-fracture effect of Aclasta.
The incidence of serious adverse events was similar between treatment groups (25.3% in the Aclasta group compared with 25.2% in the placebo group), with the exception of myocardial infarction (9 events (1.5%) in the Aclasta group compared with 2 events (0.3%) in the placebo group). None of the events were considered treatment-related by the investigator. The number of cardiac serious events in the two groups were 31 (5.3%) and 30 (4.9%), respectively (p=0.79). The most common adverse events associated with Aclasta were transient flu-like symptoms, such as fever and muscle pain.
This study was first presented at the European Congress on Osteoporosis & Osteoarthritis in March 2011.
