One 15-minute infusion of the intravenous bisphosphonate zolendronic acid more rapidly reduced the biochemical markers of bone turnover in patients with Paget's disease than was seen in a head-to-head comparison with the oral treatment risedronate (95 per cent vs. 75 per cent response rate). These findings are according to data presented at the annual meeting of the World Congress on Osteoporosis (WCO) in Brazil.
The data, from the landmark Horizon (Health Outcomes and Reduced Incidence with Zoledronic Acid ONce Yearly) Clinical Development Program, provide the basis for a marketing application recently submitted by Novartis Pharma AG to the European Agency for Evaluation of Medicinal Products (EMEA) in the European Union, for the use of zoledronic acid as a treatment for Paget's disease. This is the first filing for the use of zoledronic acid in a benign metabolic bone disease.
"The availability of bisphosphonates in recent years has revolutionized the treatment of Paget's disease," said Paul D. Miller, MD, clinical professor of medicine and medical director of the Colorado Center for Bone Research, the lead investigator of the study. "These findings suggest that a single infusion of zoledronic acid may offer a fast, effective medication with very convenient dosing. This is extremely good news for patients."
The randomized, double-blind, active-controlled trial showed that in patients with Paget's disease, one 15-minute infusion of zoledronic acid 5 mg generated a therapeutic response in 95 per cent of patients, compared with 75 per cent of patients taking 30 mg/day of oral risedronate, for 60 days (P<0.001). At the six-month follow-up, serum alkaline phosphatase (SAP) levels, a key marker for bone turnover, were normal in 89 per cent of zoledronic acid patients, compared with 56 per cent of risedronate patients (P<0.001). The primary endpoint was therapeutic response at six months, defined as 75 per cent reduction in, or normalization of, SAP, a standard measure of bone turnover.
Paget's disease of bone (also called osteitis deformans) is a painful and chronic disorder of bone metabolism, the biochemical process by which the skeletal system replenishes itself. In Paget's disease, accelerated breakdown and formation of bone produce new bone that is softer and weaker than normal. The disease causes pain, fractures and deformities that can seriously impede a patient's ability to partake in routine activities of daily living. Paget's disease can affect any part of the skeletal system, most commonly the skull, the spine and the bones of the arms, legs and pelvis. Complications of Paget's disease, the most common bone disease after osteoporosis, can include arthritis, bowing of the limbs and, if the disease affects the skull, hearing loss. Standard treatment for the disorder is primarily palliative (intended to reduce severity and ease symptoms) rather than curative.
"We are very pleased with the dramatic results we've seen so far with zoledronic acid," said Joerg Reinhardt, Head of Pharma Development, Novartis Pharma AG. "To be able to offer a convenient, single-dose treatment for potentially painful and debilitating metabolic bone diseases such as Paget's disease would represent a tremendous step forward for patients."
The Horizon Clinical Development Program is the first to study a single-dose regimen for sustaining benefits of six months or longer in Paget's disease and once-yearly dosing for osteoporosis. The Horizon program includes studies in postmenopausal osteoporosis for prevention of spine and hip fractures, the prevention of clinical fractures following a hip fracture in men and women, and the treatment of osteogenesis imperfecta in children. Worldwide, approximately 10,000 patients, in more than 200 trial centers, on four continents, are enrolled in the HORIZON program, one of the most comprehensive drug evaluation programs ever undertaken in the area of metabolic bone diseases.