The European Commission has finally granted a marketing authorization for Amgen's bone loss therapy, Prolia (denosumab), five months after CHMP issued a positive opinion.

The approval is the first for denosumab worldwide, and covers two indications - the treatment of osteoporosis in postmenopausal women at increased risk of fractures and the treatment of bone loss associated with hormone ablation in men with prostate cancer at an increased risk of fractures. It is the first product to be approved in the EU for the second indication.

The drug was turned down by the EU's Committee for Medicinal Products for Human Use (CHMP) last December Also see "Amgen’s Prolia Bone Drug Is Poised For Clearance In Europe" - Pink Sheet, 18 December, 2009.) for a third indication, use in treatment-induced bone loss in women with breast cancer.

European approval usually comes within 67 days of the CHMP opinion, but the Commission requested some additional data in the cancer setting, which led to the delay in granting the approval, the company said.

Denosumab is the next great hope for California-based Amgen, which has suffered a series of setbacks over the past few years, including a decline in sales of some of its largest-selling products, like Aranesp (epoetin alfa) and Enbrel (etanercept) Also see "Amgen's D-mab: The New EPO" - In Vivo, 1 March, 2009.).

J P Morgan, which predicts Prolia sales of around $50 million this year and $500 million next year, believes it will become a key growth driver and multibillion-dollar worldwide opportunity for Amgen. Cowen & Co and Baird analysts believe sales could peak at over $1 billion per annum.

Amgen decided last summer to boost its marketing effort for Prolia by tapping GlaxoSmithKline's expertise in primary care markets and greater multinational reach. In July 2009, the companies entered into a 50:50 profit-sharing collaboration agreement, under which both companies will commercialize Prolia for osteoporosis indications in Europe, New Zealand, Australia and Mexico, and in select emerging markets, while Amgen will commercialize it for the oncology indications. The agreement also covered other countries around the world Also see "Amgen, GSK To Team Up On Denosumab Commercialization in Europe" - Pink Sheet, 27 July, 2009.).

The deal, while complicated, will help Amgen break into the challenging PMO market, which is already laden with cheap oral generic bisphosphonates. Amgen's strength lies in its knowledge of specialists, not in primary care (Also see "GSK Denosumab Deal Gives Amgen A Leg Up In Primary Care" - Pink Sheet, 3 August, 2009.). In Europe, GSK will take the lead in marketing for the PMO indication. The company can also help with gaining national access, by working with national health authorities.

UK The First Market

The UK is likely to be the first market for denosumab, as pricing there is unregulated, with other EU launches to occur after the conclusion of country-by-country pricing negotiations.

The UK's National Institute for Health and Clinical Excellence (NICE) is expected to assess the drug for government reimbursement within months after the launch. As with other new drugs identified by the NHS as likely to have an effect on drug budgets, NICE has already started the appraisal process for denosumab in postmenopausal osteoporosis and is delaying further analysis until the drug's price is available. NICE has yet to decide on the likely publication date for the appraisal.

Will Dere, Amgen's international chief medical officer and senior vice-president, said that the company believes denosumab provides value for the money and stated that it would be priced responsibly, although he would not be drawn on specific figures. Analysts at Barclays Capital have suggested a range of $500 to $600 per annum for the product.

Untreated osteoporosis is still a high burden and unmet need in the EU, where four out of 10 women have the condition despite the availability of anti-osteoporotic medicines like bisphosphonates, Dere said in an interview. Half of women who start on osteoporosis medicines stop them after a year.

Denosumab may have advantages in terms of convenience - it is administered as a single subcutaneous injection every six months - and, unlike bisphosphonates, it does not reside long in bone.

A fully human monoclonal antibody with a novel mechanism of action, denosumab has interaction with the RANK ligand on osteoclasts, the cells that break down and recycle bone. Amgen conducted six Phase III studies of the drug in either osteoporosis or prostate cancer patients, all of which found that a 60mg subcutaneous injection of the drug every six months reduced the incidence of fractures and increased bone mineral density at all skeletal sites measured.

Submitted For U.S. Approval

Denosumab is awaiting approval in the U.S. for use in postmenopausal women at increased risk of fractures, with a PDUFA date of July 25, 2010. Amgen is responding to a complete response letter from the FDA on treatment-induced bone loss in patients with prostate and breast cancer. Also see "Aranesp Sales Continue To Slide But Amgen Reports A Solid Year" - Pink Sheet, 26 January, 2010.). Marketing submissions have also been submitted in Switzerland, Australia and Canada.

Additional indications are being evaluated for denosumab, which could expand its revenues potential. A U.S. BLA was recently filed for its use in reducing cancer skeletal-related events (SREs) -a study comparing it with Zometa (zoledronic acid) for this indication in prostate cancer patients is to be presented at a later-breaker session at the annual meeting of the American Society for Clinical Oncology (ASCO) on June 6.

Furthermore, clinical data from a Phase III study of denosumab to prevent bone metastases in prostate cancer patients is expected to become available in the second half of this year.

- John Davis (j.davis@elsevier.com)

Amgen's Prolia Gains First Regulatory Win: Market Approval in Europe

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