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EMBARGOED FOR RELEASE UNTIL 12:30 P.M. (CDT) ON SEPTEMBER 23, 2005

POTENTIAL OSTEOPOROSIS TREATMENT WELL TOLERATED, EFFECTIVE IN FIRST HUMAN STUDY

Nashville (Sept. 23, 2005) – AAE581, the first of a new class of drug compounds developed to fight osteoporosis, was well tolerated and fast acting in its first human study, according to findings being presented today by Sandip K. Roy, Ph.D., at the 27th Annual Meeting of the American Society for Bone and Mineral Research (ASBMR).

AAE581 (developed by Novartis Pharmaceuticals Corporation) targets and blocks the effects of an enzyme called cathepsin K that is responsible for the breakdown of the bone matrix. Approximately 60 percent of the weight of the bone is mineral. The rest is water and matrix, which is formed before the mineral is deposited. It is this matrix that provides bone’s scaffolding. The breakdown of the bone matrix is a common feature of osteoporosis. In animal models of osteoporosis, AAE581 reduced bone loss.

In a double-blind, placebo-controlled trial, Dr. Roy and his colleagues – at Novartis in East Hanover, NJ, and Basel, Switzerland – tested the effects of single doses (from 10 to 400 mg.) of AAE581 on 32 healthy men and women aged 18 to 45. Another 12 study participants were given placebos. The researchers reported that participants did not experience serious adverse events, and overall tolerability of AAE581 was good. The results of this small preliminary study build on animal studies and clear the way for more extensive human testing.

Dr. Roy’s team also found that six to 12 hours after participants who received more than 25 mg. of AAE581 took the compound, blood serum concentrations of a biochemical marker (CTx) known to indicate bone breakdown dropped by 90%. The process of bone breakdown – also called bone resorption – is increased in people with osteoporosis. Reducing levels of bone breakdown is a strategy for osteoporosis treatment. With AAE581, bio-marker levels returned to pre-treatment levels within 48 hours. In contrast, bisphosphonate medications prescribed to treat osteoporosis have a more gradual onset of effect. AAE581 has a shorter half-life compared to bisphosphonates, but it is long enough to support once daily dosing. Bisphosphonates have a very long half-life, estimated to be many months to several years. In contrast, AAE581 is quickly eliminated from the body and does not accumulate in the bone. Unlike bisphosphonates, AAE581 also has a fast onset and offset of effect on biomarkers, raising the potential for a faster onset of effect on bone mineral density and fracture prevention.

ASBMR President-Elect Elizabeth Shane, M.D., notes: “This work is significant because it provides evidence for a short-acting but potent agent that suppresses bone turnover markers. A class of drugs with the potency of bisphosphonates, yet with a more rapid onset and offset than bisphosphonates, could provide another therapeutic option that may prove particularly useful preventing bone loss in situations where the cause of bone loss is acute and/or temporary. Examples of such situations are space flight, immobilization, or relatively short-term use of high-dose glucocorticoids. These agents would also be useful for more chronic situations like postmenopausal osteoporosis.”

Please note that the results of a study of AAE581 in a monkey model of osteoporosis are also being presented at ASBMR’s September 23rd press conference. (See “Cathepsin-K Inhibitor Protected Against Bone Loss in Monkey Model of Osteoporosis.”)

The study discussed in this press release was funded by Novartis. Dr. Roy is a Novartis employee holding Novartis stock, options or bonds.

To obtain a copy of the scientific abstract, contact Ms. Melissa Haynes (contact information above).

The ASBMR Annual Meeting is the preeminent international scientific meeting on bone and mineral research. More than 5,300 medical professionals and scientists from around the world are expected to attend the September 23-27, 2005, meeting in Nashville, where more than 1,900 research abstracts will be presented. The ASBMR is the foremost professional, scientific and medical society for the promotion of bone and mineral research and the translation of that research into clinical practice. To learn more, visit the ASBMR website at www.asbmr.org.

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