Denosumab for the prevention and treatment of skeletal related events (SRE) from bone metastases

Denosumab (Prolia), under development by Amgen, is the first fully human monoclonal antibody (MAb) in late stage clinical development that specifically targets RANK Ligand (RANKL), an essential regulator of osteoclasts, the cells that break down bone. Among other indications, Prolia is being investigated for the treatment and prevention of bone loss resulting from hormone ablation in patients with breast and prostate cancer, as well as for its potential to delay bone metastases and inhibit and treat bone destruction in patients with multiple myeloma and across many stages of cancer. In direct evaluation against zoledronic acid (Zometa; Novartis), the current standard of treatment of bone loss associated with cancer metastasized to the bone, denosumab was superior to Zometa in preventing skeletal related events (SRE) and delayed worsening of bone pain in a phase III clinical trial of 2,046 patients with advanced breast cancer. In addition, denosumab also presented some potential tolerability advantages for many patients, including a lower incidence of renal toxicity and acute phase reactions, combined with the convenience of a monthly SC injection. Similarly, in another phase III clinical trial, denosumab was non-inferior to Zometa in the treatment of bone metastases in 1,776 patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma and superior to Zometa in delaying the time to the first on-trial skeletal related event (SRE) for a hazard ratio (HR) of 0.82, and reducing the rate of multiple SRE (HR=0.82) in patients with hormone-refractory prostate cancer (HRPC). In May 2010, Amgen submitted a BLA to the FDA for denosumab based on approximately 5,700 patients with advanced metastatic cancer who were enrolled in 3 pivotal, phase III clinical trials (protocol ID: 20050244; NCT00330759, 20050136; NCT00321464, and: 20050103; NCT00321620) evaluating denosumab versus zoledronic acid (Zometa; Novartis). In May 2010, Prolia was approved in the European Union (EU) for the treatment of osteoporosis in postmenopausal women at increased risk of fractures, and for the treatment of bone loss associated with adrogen deprivation therapy (ADT) in men with nonmetastatic prostate cancer at increased risk of fractures. The FDA also approved Prolia for the treatment of postmenopausal women with osteoporosis at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients with refractory disease or who cannot tolerate other available osteoporosis treatments.

Noxafil against invasive fungal infections

In pharmacoeconomic studies published in the American Journal of Health System Pharmacy http://www.ajhp.org/cgi/content/abstract/65/23/2237 and in Value in Health http://www3.interscience.wiley.com/journal/121636980/abstract, comparing Noxafil (posaconazole) Oral Suspension, with fluconazole or itraconazole, prophylaxis with Noxafil in certain invasive fungal infections in severely immunocompromised patients reduced overall costs. Such infections represent a significant cause of morbidity and mortality in these patients. In fact, patients undergoing hematopoietic stem cell transplants (HSCT) who develop such an infection have a high mortality rate varying between 50%-90% (Bow EJ, etal, Cancer 2002;94:3230-46).