The European Commission has approved once-yearly Aclasta (zoledronic acid 5 mg) for the treatment of osteoporosis in men who are at increased risk of fractures, and broadened the Aclasta label to include reduction of new clinical fractures in both men and postmenopausal women with osteoporosis who have recently suffered a hip fracture.
Osteoporosis is an important health concern for men, with an estimated one out of five over the age of 50 experiencing an osteoporotic fracture. In cases of hip fracture - one of the most serious consequences of osteoporosis - the mortality rate is higher in men than women in the year following the fracture. Over the first six months, men are approximately twice as likely to die as women of a similar age.
"Despite the severity and the large numbers affected, osteoporosis in men has received very little attention," said Steven Boonen, Professor of Medicine at the Leuven University Centre for Metabolic Bone Diseases and Division of Geriatric Medicine in Belgium. "Most people view osteoporosis solely as a 'woman's disease', but this is not the case. It is vital that men with osteoporosis have the same efficacious treatment options available to them as women, and the announcement is therefore especially welcome."
In addition, the EU label has been extended to include data from the landmark recurrent fracture trial, involving more than 2,100 patients, showing that once-yearly Aclasta reduced the risk of new clinical fractures by 35 per cent in men and postmenopausal women who have recently had a low-trauma hip fracture (e.g. due to a fall from standing height or less).
The new label also includes data from the same study showing that all-cause mortality was significantly reduced by 28 per cent in the Aclasta-treated group compared to those receiving placebo (101 vs. 141 deaths respectively). Aclasta is the only osteoporosis treatment to demonstrate these benefits in patients after a recent low-trauma hip fracture.
"For both men and women, hip fracture can be a potentially life-threatening consequence of osteoporosis," said Prof Boonen. "Hip fracture is associated with a high risk of morbidity and mortality, and it is encouraging that we now have a treatment proven to reduce the risk of a new fracture after this has occurred."
In 2000, approximately 1.6 million hip fractures occurred worldwide, and in Europe the number of hip fractures was estimated at around 179,000 for men and 711,000 for women.
"At Novartis we are committed to putting the needs of the patient first," said Trevor Mundel, global head of Development Functions at Novartis Pharma AG. "More than a quarter of a million patients have already been treated with Aclasta, and these new approvals mean that two new populations can be treated with this once-yearly dosing regimen. This once yearly dosing represents a convenient way to help protect both men and women against the life-threatening consequences of osteoporosis."
The EU Commission approval, following a positive opinion issued in July by the Committee for Medicinal Products for Human Use (CHMP), will apply in all 27 EU member states plus Iceland and Norway.
Approval was based on pivotal data from the recurrent fracture trial, involving more than 2,100 men and women aged 50 and above who had recently suffered a low-trauma hip fracture. Aclasta was shown to reduce the risk of new clinical fractures by 35 per cent compared to patients receiving placebo, and to increase bone mineral density (BMD). The risk of new spine fractures was reduced by 46 per cent.
A two-year head-to-head trial comparing Aclasta with weekly oral alendronate provided additional data on the treatment of male osteoporosis. This study involving more than 300 osteoporotic men showed that Aclasta preserved and improved lumbar spine BMD at 24 months.
Aclasta, which is administered by once-yearly infusion, was approved in the EU in October 2007 for the treatment of osteoporosis in postmenopausal women. It is now approved in more than 80 countries in this indication and is currently available in more than 70 countries including the US, Canada, Brazil and most EU member states. Aclasta is available in the US under the trade-name Reclast.
Aclasta/Reclast is the only treatment for postmenopausal osteoporosis approved in the EU and US to reduce the risk of fractures at all key sites, including the hip, spine and non-spine (e.g. wrist and rib).
In June 2008, the Food and Drug Administration (FDA) broadened the US label to include data showing the reduced risk of new clinical fractures in patients who have recently had a low-trauma hip fracture. Novartis has applied for an indication in the US for the treatment of osteoporosis in men.
Reclast is covered by Medicare and most commercial health plans in the US. Reimbursement discussions are continuing in many other countries to maximize patient access to this innovative medication. Novartis is seeking to meet the needs of patients and physicians in different countries by establishing a network of infusion centers to promote safe and correct administration of Aclasta.
Aclasta is also approved in more than 80 countries for the treatment of Paget's disease of the bone, the second most common metabolic bone disorder.
Aclasta has a demonstrated tolerability profile. The most common adverse events associated with Aclasta were transient post-dose symptoms such as fever and muscle pain. Most of these symptoms occurred within the first three days following Aclasta administration and resolved within three days. The incidence of such post-dose symptoms can be reduced with the administration of paracetamol or ibuprofen shortly after Aclasta infusion.
Zoledronic acid, the active ingredient of Aclasta, is also available under the trade-name Zometa for use in oncology indications.