FDA has given Amgen’s Prolia the go-ahead to treat postmenopausal women with osteoporosis who are at high risk for fractures. Last week Amgen gained EU Marketing Authorization for the drug in the 27 member states plus Norway, Iceland, and Liechtenstein.
Prolia is also indicated for patients in the U.S. who have failed or are intolerant to other available osteoporosis therapies. A 60 mg subcutaneous injection is recommended once every six months, according to the agency.
FDA sanction came more than a month ahead of schedule; the PDUFA date was set as July 25. The drug is heralded as Amgen’s biggest growth drug. The firm has been hit recently by lower sales from Aranesp and Epogen due to safety issues and reimbursement changes. Additionally, there is the potential of biosimilar versions of its drugs to further decrease the company’s franchise.
Prolia was approved with a risk evaluation and mitigation strategy that includes a medication guide for patients and communications to healthcare providers that explains the risks and benefits of the drug. Amgen will also conduct post-marketing surveillance and is already gathering data from extension studies in more than 4,500 women who will have exposure to Prolia for up to 10 years.
Additionally, the company will implement an international Prolia long-term safety observational study to assess prespecified adverse events of special interest based on seven existing data systems from five countries, which will include healthcare administrative databases, electronic medical records, and national health registries.
Serious infections leading to hospitalizations were reported more frequently in the Prolia-treated patient group. Serious skin infections and infections of the abdomen, urinary tract, and ear as well as endocarditis were also more frequent in patients treated with Prolia. The drug also causes significant suppression of bone turnover and this suppression may contribute to the occurrence of osteonecrosis of the jaw (ONJ). Epidermal and dermal adverse events such as dermatitis, rashes, and eczema as well as pancreatitis have been reported, according to Amgen. The most common adverse reactions (>5% and more common than placebo) were back pain, pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis.
“The label mentions the expected warnings such as ONJ, dermatologic AE, hypocalcemia, serious infections, and suppression of bone turnover,” notes Joshua Schimmer, M.D., and Steve Y. Yoo, biotechnology equity research analysts at Leerink Swann. “Interestingly, malignancy was not listed as one of the warnings, and the label included the language ‘causal relationship to drug exposure has not been established.’ This is a big win for the postmenopausal indication, which gives us much greater optimism for Dmab sales.”
Prolia will cost $825 per 60 mg injection, which is competitive with other branded osteoporosis therapies while reflecting its positive clinical profile for patients at high risk for fracture, Amgen notes. Annual cost would be $1,650 versus about $1,200–1,300 annually for oral bisphosphonates, point out Dr. Schimmer and Yoo.
“Today’s FDA approval of Prolia is the culmination of a scientific journey that started more than 15 years ago with Amgen’s discovery of an essential pathway that regulates bone metabolism,” says Kevin Sharer, chairman of the board and CEO of Amgen.
Prolia is reportedly the first FDA-approved compound that targets the RANK ligand, a regulator of osteoclasts. The drug works to decrease the destruction of bone and increase bone mass and strength.
FDA approval was based on a three-year study involving 7,808 postmenopausal women ages 60 to 91 years with osteoporosis. Treatment with Prolia resulted in greater bone density, stronger bones, and reduced risk for vertebral, hip, and nonvertebral fractures measured at three years.
Last month, Amgen submitted an NDA for Prolia to market the drug for reduction of fractures and other skeletal-related problems in patients with advanced cancer. Prolia was compared with Novartis' Zometa in late-stage clinical trials with patients who had advanced breast or prostate cancer.