Osteoporosis – new options for bone loss

The osteoporosis therapeutics market has evolved over the last 10 years, moving away from hormone replacement therapies (which dominated sales in the early 1990s), to the bisphosphonates, the current market leaders. Biotechnology products, however, are starting to make an impact: since its market launch at the end of 2002, Lilly’s Forteo (recombinant parathyroid hormone, or teriparatide) has seen significant growth, and now represents 92% of its ATC therapeutic class (H4V, 'other hormones').

Nevertheless, the market remains dominated by the bisphosphonates, in particular Merck & Co's Fosamax (alendronate), which saw its sales exceed $3 billion in 2004; it has 48% of the M5B 'bone calcium regulators' ATC class. Fosamax saw fixed-rate growth of 12% in 2004, while the second leading product in the class, Procter & Gamble and sanofi-aventis' Actonel (risedronate), grew 50%. There are two other main osteoporosis therapies: Lilly's selective oestrogen receptor modulator Evista (raloxifene) had 74% of the G3H 'other sex hormones' class in 2004 and registered 5% growth, while Novartis' Miacalcic (salmon calcitonin), the leading product in the H4A 'calcitonins' class, had flat sales from 2003.

Leading osteoporosis therapies, 2004

Source: IMS MIDAS

New therapy available

The newest osteoporosis therapy on the market is Servier’s Protelos (strontium ranelate), a daily oral therapy that was launched in Germany in October 2004, with further launches across Europe planned during 2005. Data were presented from clinical trials of Protelos at the 5th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (held in Rome, 16-19 March 2005), demonstrating it to have a unique dual mechanism of action - simultaneously increasing bone strength and decreasing bone resorption, resulting in a rebalance of bone turnover in favour of bone formation.

Results from Phase III trials showed significant and sustained vertebral antifracture efficacy in patients with prevalent vertebral fracture; the relative risk of clinical vertebral fracture was reduced by 52% after one year and by 38% after three years compared with placebo. Protelos also reduced the relative risk of all peripheral fractures by 16%. The agent was well tolerated and significantly improved patients’ quality of life compared with placebo.

Extended-release products on the way

At the end of March 2005, the FDA approved a once-monthly formulation of Roche and GlaxoSmithKline’s Boniva (ibandronate), and it was launched in the US on April 18 2005; ibandronate has been marketed since 1996 for hypercalcaemia of malignancy. Data from the MOBILE study of the once-monthly formulation of Boniva were presented at the 5th ECCEO, showing that a once-monthly tablet was an effective treatment for osteoporosis. Roche and GSK are also developing an intravenous formulation that would only need to be injected every three months, while Novartis is developing a once-yearly intravenous formulation of Aclasta (zoledronate), already approved for Paget's disease, in Phase III trials.

There is clear patient demand for these less frequently taken bisphosphonates. The compounds have a strict treatment regime, which involves remaining upright and not eating, drinking (except water) or taking other medications for a period of time before and after therapy. This results in problems with patient compliance. Studies presented at the 5th ECCEO highlighted the need for improved compliance and persistency in the treatment of osteoporosis:

• bisphosphonates, administered weekly and daily, were associated with poor compliance, thus, outcomes shown in clinical trials were not being achieved in ‘real world’ practice, leaving patients at risk of further fractures
• only 54% of women continued taking their daily bisphosphonate therapy for the whole year; 63% of women continued taking a weekly bisphosphonate
• over a 12-month period, women who kept taking their therapy continuously with a gap of no more than 45 days represented 19% of daily users and 22% of weekly users
• 78% of osteoporosis patients felt that taking medication less often was a very important factor, and 63% of patients taking a weekly treatment would prefer a once-monthly treatment option.

In April 2005, the FDA approved Merck & Co's Fosamax Plus D, a single once-weekly tablet combining Fosamax with cholecalciferol, a vitamin D. An injectable recombinant parathyroid hormone, Preos (Preotact in Europe), was filed for approval in the EU in March 2005 by NPS, which is preparing an NDA filing in the USA. As shown in the table below, a number of other products for osteoporosis are also waiting in the wings. 

Late-stage osteoporosis products

Amgen reported one-year data from a multi-centre Phase II trial of AMG 162 in post-menopausal women at the 5th ECCEO. The study evaluated twice yearly treatment with AMG 162, administered by subcutaneous injection, compared with placebo and with an open label comparison to Fosamax, in 412 healthy post-menopausal women with low bone mineral density (BMD). Results showed that all doses of AMG 162 significantly increased BMD at the hip compared with placebo at 12 months. The antibody also increased total hip BMD, similar to or greater than that seen with Fosamax over the same time. AMG 162 was well tolerated, with no serious adverse events reported, no patients withdrawing from the trial and no increased incidence of infections.

This article was written by Carolyn Hughes, Deputy Executive Editor of R&D Focus. Data from the 5th ECCEO were reported in IMS LifeCycle R&D Focus and in Drug News. Now available is IMS Biotech Market Analyzer - the most detailed and comprehensive analysis tool for the global biotech market. The database publication provides information on biotech sales performance in both the retail and non-retail sectors world-wide, by therapy class, corporation and geographic region. For further information about any of these products, please contact Stephanie Earle via e-mail or call +44 207 393 5515.