Novartis Pharmaceuticals AG (BASEL, Switzerland) announced that Aclasta® (zoledronic acid 5 mg) has received EU approval as the first once-yearly treatment for women with postmenopausal osteoporosis. The European Commission decision applies to all 27 member states, Norway, and Iceland. The announcement closely follows the recent US approval in August 2007, when the FDA approved Aclasta under the brand name Reclast®. The drug is the only treatment approved in the EU and US to reduce the risk of fractures in areas of the body including the hip, spine, and nonspine (eg, wrist and rib) typically affected by osteoporosis.

Unlike oral bisphosphonate therapies taken daily, weekly, or monthly, Aclasta is given as a once-yearly 15-minute intravenous infusion. According to Novartis, data show that more than 70% of patients prefer a once-yearly infusion of Aclasta to a weekly tablet.

The regulatory approvals were based on efficacy and safety data from another study, the 3-year Pivotal Fracture Trial involving more than 7700 women. In this study, Aclasta was shown to increase bone strength and reduce by 70% the risk of spine fractures and by 41% the risk of hip fractures. The reduction in spine fractures was sustained over 3 years, and bone mineral density increased significantly by 6.7% in the spine and by 6% in the hip of women taking Aclasta compared with placebo.

In this trial, an increased number of cases of atrial-fibrillation serious adverse events were observed in women given Aclasta compared with those on placebo (1.3% vs 0.6%, respectively). However, this finding has not been observed in other clinical studies or in postmarketing experience with over 1.5 million patients treated with zoledronic acid for oncology indications.

Furthermore, results of the first-ever clinical study (the Recurrent Fracture Trial) in patients with osteoporosis who had suffered a hip fracture show a once-yearly infusion of Aclasta reduced by 35% the risk of any type of subsequent osteoporotic fracture compared with placebo-treated patients. The findings are published in the September issue of The New England Journal of Medicine.

This trial, involving more than 2100 men and women, also found the risk of death was significantly reduced by 28% in the Aclasta patient group compared with the placebo group (101 vs 141 deaths, respectively). Atrial-fibrillation serious adverse events occurred in 1.1% of Aclasta-treated patients compared with 1.3% of placebo-treated patients. No spontaneous reports of osteonecrosis of the jaw—a rare occurrence in the osteoporosis population treated with bisphosphonates—were seen in either the Pivotal Fracture Trial or Recurrent Fracture Trial.

Aclasta was found to be generally safe and well tolerated in clinical trials; common adverse events were transient postdose symptoms such as fever and muscle pain. Most of these symptoms occurred within the first 3 days following Aclasta administration and resolved within 3 days. The incidence of postdose symptoms can be reduced with the administration of paracetamol or ibuprofen following Aclasta infusion.

Aclasta is now approved in more than 30 countries for the treatment of postmenopausal osteoporosis, and in more than 60 countries including Canada, the US, and the EU for the treatment of Paget's disease, the second most common metabolic bone disorder. Additional studies are ongoing to examine treatment of corticosteroid-induced osteoporosis, male osteoporosis, and prevention of bone loss in osteopenic patients.