Just when things couldn't look any gloomier for Amgen. After a series of setbacks the Big Biotech is relying heavily on the future success of its late-stage denosumab osteoporosis therapy. One of the main attractions of the antibody therapy is its convenient route of administration: the drug will only have to be infused twice a year--a big improvement over weekly pill-taking that can lead to poor patient compliance.Too little too late?
In a three-year study of nearly four thousand patients, Novartis' once-a-year infusion Reclast (a.k.a. Aclasta, a.k.a. Zometa) was shown to decrease bone turnover and improve bone density at 12 months in postmenopausal women with osteoporosis. Results were published yesterday, in this week's New England Journal of Medicine.
Analysts have predicted the drug could be approved in that indication later this year. Although side effects included a higher rate of atrial fibrillation in the treatment group, the drug is on the market for other conditions, such as Paget's disease and the A-fib wasn't seen by observers as a deal breaker in osteoporosis either.
Amgen shares were down nearly two percent yesterday. Denosumab--currently being tested in a handful of late-stage trials, comprising a variety of oncology and bone-related indications--won't hit the market for postmenopausal osteoporosis until at least 2009. We'll take a look at Amgen's post-EPO R&D prospects in the May IN VIVO.
Bisphosphonate drugs for Osteoporosis, like Fosamax and Actonel, are taken up by osteoclasts with resulting loss of osteoclast activity and inhibition of bone resorption, and bone remodeling.
ReplyDeleteAlthough DEXA scanning confirms increased bone density and studies such as the FIT suggest reduced fracture rate, Susan Ott, MD raises questions about the long term safety of bisphosphonates. Although the bisphosphonates appear to have short term benefits, she speculates that after 5 years of use, there is severe suppression of bone formation with negative effects such as microdamage and brittleness.
Spontaneous Fractures of the Mid-Femur
Jennifer P. Schneider, MD, PhD reports a 59-year old previously healthy woman on long-term alendronate. While on a subway train in New York City one morning, the train jolted, and the woman shifted all her weight to one leg, felt a bone snap, and fell to the floor, suffering a spontaneous mid -femur fracture. This is not an isolated report.
Avacular Necrosis of the Jaw
Dimitrakopoulos reports on 11 patients presenting with necrosis of the jaw, claiming this to be a new complication of bisphosphonate therapy administration, i.e. osteonecrosis of jaws. He advised clinicians to reconsider the merits of the rampant use of bisphosphonates. Osteonecrosis of the jaw is a common finding in pycnodysostosis. The bisphosphonates recreate the same clinical profile of spontaneous mid femur fractures, failure of bone healing and jaw necrosis which tormented the famous French artist, Toulouse Lautrec.
For links to references and more information see my newsletter:
Fosamax, Actonel, Osteoporosis and Toulouse Lautrec's Disease
Jeffrey Dach MD