Aclasta(R)/Reclast(R) Better Than Risedronate For Prevention And Treatment Of Bone Loss In Patients With Steroid-induced Osteoporosis

Main Category: Bones / Orthopedics
Also Included In: Respiratory / Asthma;  Arthritis / Rheumatology;  GastroIntestinal / Gastroenterology
Article Date: 14 Apr 2009 - 4:00 PDT

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A study published in The Lancet1 shows that a once-yearly infusion of Aclasta®/Reclast® (zoledronic acid 5 mg)* is significantly more efficacious than risedronate in preventing and treating bone loss in men and women with osteoporosis caused by glucocorticoids, often referred to as corticosteroids or steroids1.

The one-year study included more than 800 patients and investigated both the prevention and treatment of glucocorticoid-induced osteoporosis (GIO), comparing the efficacy of Aclasta/Reclast with daily oral risedronate, an established GIO therapy.

The greater efficacy of Aclasta/Reclast on bone mass was evident at six months after the start of the study1. This is important in the prevention of GIO because the reduction of bone mass and its associated increase in fracture risk can occur even within three months of initiating glucocorticoid therapy1.

Glucocorticoids are widely used to treat inflammatory conditions such as asthma, rheumatoid arthritis and inflammatory bowel disease2. It is estimated that between 700,000 and 1,300,000 adults in Western Europe and between 1,500,000 and 2,700,000 adults in the US are receiving prolonged courses of oral glucocorticoids4,5. Up to 50% of patients receiving long-term glucocorticoid therapy are at increased risk of fracture due to osteoporosis as their use is associated with side effects such as bone loss, and consequently osteoporosis2.

"Currently, the established therapy for the prevention and treatment of GIO are oral bisphosphonates which have been associated with poor compliance," said Professor David M. Reid, Head of the Division of Applied Medicine at the University of Aberdeen, UK, and lead researcher of the study. "A once-yearly intravenous infusion has been shown to be fast-acting1 and significantly efficacious, and is therefore a valuable option to treat GIO patients and help protect them for a full year from an increased risk of osteoporotic fractures."

Aclasta/Reclast is also approved in more than 80 countries to treat osteoporosis in men and postmenopausal women, to reduce new clinical fractures in men and postmenopausal women who have recently suffered a low trauma hip fracture, and to treat Paget's disease of the bone. Recently Reclast has been approved by the Food and Drug Administration in the US to treat and prevent GIO in men and women who are expected to remain on glucocorticoids for at least 12 months.

Aclasta/Reclast has been used by more than 425,000 patients worldwide since its launch in 20073. Novartis is also pursuing the indication for GIO treatment in the EU, which is expected later this year.

The study of 833 men and women published in The Lancet, investigated both prevention (288 patients) and treatment (545 patients) of GIO1, and had several advantages over previous trials designed to determine the effects of bisphosphonate therapy on GIO. These include the large sample size, the generalizability of the results by inclusion of both GIO prevention and treatment subgroups, and excellent retention rate. A limitation of this trial was its short duration (12 months), but many diseases requiring glucocorticoid treatment are medium-term therapies only (12-18 months). These data were first presented at the ECCEO congress in 20086.

The study showed that a single intravenous infusion of Aclasta/Reclast resulted in significantly greater increase in bone mineral density (BMD) of the lumbar spine and femoral neck, trochanter and total hip compared to once-daily oral risedronate1. The greater efficacy of Aclasta/Reclast was evident at six months after treatment initiation1. Aclasta/Reclast was superior at increasing lumbar spine BMD at 12 months compared to once-daily risedronate (Actonel), in both the treatment group (Reclast 4.1%, risedronate 2.7%; P=0.0001) and prevention group (Reclast 2.6%, risedronate 0.6%; P<0.0001)1.

Results from this study show that Aclasta/Reclast is generally safe and well-tolerated1. The most common adverse events associated with Aclasta/Reclast were transient post-dose symptoms such as fever and muscle pain1. The majority of these symptoms occurred in the first three days after Aclasta/Reclast administration and resolved within that same period of time1. Post-dose symptoms can be reduced by taking paracetamol or ibuprofen shortly after the Aclasta/Reclast infusion7.

In this trial there were no cases of osteonecrosis of the jaw, delayed fracture healing or esophageal cancer, and no evidence of an increased risk of atrial fibrillation1.

The active ingredient in Aclasta/Reclast is zoledronic acid, which is also available in a different dosage under the brand name Zometa® (zoledronic acid 4 mg) for use in certain oncology indications.

Disclaimer

The foregoing release contains forward-looking statements that can be identified by terminology such as or similar expressions, or by express or implied discussions regarding potential new indications or labeling for Reclast or regarding potential future revenues from Reclast. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Reclast to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Reclast will be approved for any additional indications or labeling in any market. Nor can there be any guarantee that Reclast will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Reclast could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; the company's ability to obtain or maintain patent or other proprietary intellectual property 3/4

protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis AG provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, preventive vaccines, diagnostic tools, cost-saving generic pharmaceuticals, and consumer health products. Novartis is the only company with leading positions in these areas. In 2008, the Group's continuing operations achieved net sales of USD 41.5 billion and net income of USD 8.2 billion. Approximately USD 7.2 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 96,700 full-time-equivalent associates and operate in more than 140 countries around the world.

References

1. Reid DM, Devogelaer J-P, Saag K, Roux C, et al. Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial. Lancet 2009; 373: 1253-63

2. Sambrook PN. Corticosteroid Osteoporosis: Practical Implications of Recent Trials. JB M R 2000; 15:1645-1649.

3. Novartis data on file. Novartis Pharma AG; March 11, 2008.

4. Gluck O, Colic G. Recognizing and Treating Glucocorticoid-Induced Osteoporosis in Patients with Pulmonary Diseases. CHEST 2004; 125: 1859-1876.

5. United Nations. Department of Economic and Social Affairs. Population Division. The 2008 Revision. Western Europe and United States of America Population Statistics. Available at: http://esa.un.org/unpp. Last accessed 30 March, 2009. The estimated figures for glucocorticoid use in Western Europe and the US were calculated by extrapolating the percentage of UK adults receiving oral glucocorticoids at any given time (between 0.5% and 0.9% of the adult population) to the populations of Western Europe (145 million adults) and the US (300 million adults).

6. Reid DM, Devogelaer J-P, Saag K, et al. A single infusion of zoledronic acid 5 mg is significantly more effective than daily oral risedronate 5 mg in increasing bone mineral density of the lumbar spine, hip, femoral neck and trochanter in patients with glucocorticoid-induced osteoporosis, European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ECCEO) in Istanbul, Turkey, April 11, 2008.

7. Aclasta Summary of Product Characteristics. West Sussex, United Kingdom: Novartis Europharm Limited, 2008.

Source
Novartis

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