Aclasta Receives US FDA Approval As First And Only Once-Yearly Treatment For Women With Postmenopausal Osteoporosis

Main Category: Regulatory Affairs / Drug Approvals
Also Included In: Bones / Orthopaedics;  Women's Health / Gynecology;  Pharma Industry / Biotech Industry
Article Date: 22 Aug 2007 - 1:00 PDT

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Aclasta (zoledronic acid 5mg) has been approved by the US Food and Drug Administration (FDA) under the brand name Aclasta® Injection as the first and only once-yearly medicine for postmenopausal osteoporosis, offering an important new approach to the treatment of a bone disease affecting eight million women in the US1.

Unlike oral bisphosphonate therapies that have to be taken daily, weekly or monthly, Aclasta is given as a once-yearly 15-minute intravenous (IV) infusion. This means with a single treatment a patient can receive a full year's protection against the effects of osteoporosis - a disorder that causes bones to break easily.

"The fact that Aclasta is highly effective and can be administered once-yearly represents a major milestone in the treatment of postmenopausal osteoporosis," said Felicia Cosman, MD, Professor of Clinical Medicine, Columbia University.

"For the first time we can ensure women receive a full year of the treatment they need to protect their bones," said Dr. Cosman.

The US approval comes a few weeks after the Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion recommending approval for the medicine in the European Union. The European Medicines Agency (EMEA) generally follows the CHMP's recommendations and is expected to issue marketing authorisation within three months.

The regulatory submissions were based on efficacy and safety data from the three-year Pivotal Fracture Trial, which showed that Aclasta increases bone strength and reduces fractures in areas of the body typically affected by osteoporosis, including the hip, spine and non-spine (i.e. hip, wrist, arm, leg, rib). Aclasta is the only treatment proven to reduce fractures across all of these key sites.

In this study involving more than 7,700 women, Aclasta reduced the risk of spine fractures by 70% and hip fractures by 41% (The New England Journal of Medicine, May 3, 2007) 2. The reduction in spine fractures was sustained over three years (60% in year one, 71% in year two, and 70% in year three). Bone mineral density increased significantly in the spine by 6.7% and the hip by 6% in women on Aclasta compared to placebo2.

"Aclasta has shown significant efficacy in protecting women against fractures in all the common osteoporotic fracture sites, while demonstrating a favorable safety profile," said James Shannon, MD, Global Head of Development at Novartis Pharma AG. "It is our hope that this innovative once-yearly dosing regimen will have a positive impact on the management of this potentially devastating condition."

The need for effective treatments is pressing, with one out of every two women over the age of 50 suffering an osteoporotic fracture in her lifetime1. The disease is responsible for 1.5 million fractures in the US every year1, some of which can have severe consequences. Approximately 20% of women over the age of 50 who suffer a hip fracture will die within one year1.

Osteoporotic fractures are responsible for an estimated 800,000 emergency room visits, 500,000 hospitalizations, 180,000 nursing home placements, and 2.6 million physician visits in the US each year3, costing the healthcare system approximately $12.2 to 17.9 billion annually3.

"Osteoporosis is a serious disease affecting millions of people in this country," said Leo Schargorodski, executive director of the National Osteoporosis Foundation (NOF). "NOF welcomes new FDA approved treatment options, such as Aclasta, that give patients a choice when it comes to taking their osteoporosis therapy."

Aclasta is approved in more than 60 countries, including the US, Canada and the EU for the treatment of Paget's disease, the second most common metabolic bone disorder. Additional studies are ongoing to examine the use of Aclasta to prevent fractures following a hip fracture in men and women, treatment of corticosteroid-induced osteoporosis, and male osteoporosis.

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

Aclasta is contraindicated in patients with hypocalcemia (low blood calcium) and those who are allergic to zoledronic acid. Aclasta contains the same active ingredient found in Zometa. Patients already being treated with Zometa should not be treated with Aclasta. Aclasta should not be used during pregnancy because of potential harm to the fetus. Aclasta is not recommended for use in patients with severe renal impairment (creatinine clearance <35 mL/min) and infusion time should not be less than 15 minutes.

The most common side effects associated with Aclasta are fever; pain in the muscles, bones or joints; flu-like symptoms; and headache. These symptoms usually occur within the first three days following Aclasta administration and usually resolve within 3 to 4 days of onset but resolution could take up to 7 to 14 days. Patients have reported severe bone, joint and/or muscle pain after using bisphosphonates. Osteonecrosis of the jaw (ONJ) has been reported rarely in postmenopausal osteoporosis patients treated with bisphosphonates. A routine oral examination should be performed by the prescriber prior to initiation of bisphosphonate treatment. Hypocalcemia may occur with Aclasta therapy. In the Pivotal Fracture Trial, an increased number of cases of serious atrial fibrillation were observed in women given Aclasta compared to those on placebo (1.3% vs. 0.4% respectively)2. The timing of these events suggest that they were not related to the acute infusion. This finding has not been observed in other zoledronic acid clinical studies and in post-marketing experience from more than 1.5 million patients treated with Zometa.

All patients with Paget's disease should receive 1500 mg of calcium in divided doses and 800 IU of vitamin D daily, particularly in the two weeks following Aclasta administration. It is recommended that patients with postmenopausal osteoporosis take calcium and vitamin D supplements, if dietary intake is not sufficient.

For more information about Aclasta, visit http://www.reclast.com or http://www.Aclasta.com.

Disclaimer

The foregoing press release contains forward-looking statements that can be identified by the use of forward-looking terminology such as "potential", "anticipated", "generally follows", "expected", "hope", "will", or similar expressions, or by express or implied discussions regarding potential future regulatory approvals of Aclasta, or potential future sales of Aclasta. Such forward-looking statements reflect the current views of Novartis regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Aclasta will be approved for sale, or for any additional indications or labeling in any market, or that Aclasta will reach any particular level of sales.

In particular, management's expectations regarding Aclasta could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected additional analysis of existing clinical data, and unexpected new clinical data; competition in general; government, industry, and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; as well as the additional factors discussed in Novartis AG's Form 20-F filed 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 described herein as anticipated, believed, estimated or expected. Novartis is providing this information as of this date and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

About Novartis

Novartis AG (NYSE: NVS) is a world leader in offering medicines to protect health, cure disease and improve well-being. Our goal is to discover, develop and successfully market innovative products to treat patients, ease suffering and enhance the quality of life. We are strengthening our medicine-based portfolio, which is focused on strategic growth platforms in innovation-driven pharmaceuticals, high-quality and low-cost generics, human vaccines and leading self-medication OTC brands. Novartis is the only company with leadership positions in these areas. In 2006, the Group's businesses achieved net sales of USD 37.0 billion and net income of USD 7.2 billion. Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ more than 100,000 associates and operate in over 140 countries around the world.

http://www.novartis.com

References

1 National Osteoporosis Foundation. About Osteoporosis: Fast Facts. Available at: http://www.nof.org/osteoporosis/diseasefacts.htm Accessed on June 7, 2007.

2 Black D, Delmas, S, Eastell R et al for the HORIZON Pivotal Fracture Trial. Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis. NEJM 2007; 356(18):1809-22.

3. U.S. Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. 2004.

http://www.novartis.com