New Data Show Bonviva Effective as a Once-Monthly Oral Formulation for Osteoporosis

Main Category: GastroIntestinal / Gastroenterology
Article Date: 04 Oct 2004 - 0:00 PST

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New data presented for the first time at the 26th Annual Meeting of the American Society for Bone Mineral Research (ASBMR), show Bonviva™ (ibandronate) to be effective and well tolerated as a once-monthly oral bisphosphonate in the treatment of post-menopausal osteoporosis1,2,3,4, an indication which is currently being evaluated by the European Authorities.

The efficacy of Bonviva once-monthly was clearly demonstrated by the first presentation of the results of the MOBILE (Monthly Oral IBandronate in LadiEs) study1,2,3,4. These findings suggest Bonviva may be a convenient alternative to current daily and weekly oral bisphosphonate regimens, as Bonviva is expected to offer the efficacy of a bisphosphonate with the simple convenience of just 12 tablets a year, potentially enhancing treatment adherence and compliance for patients.

One-year data from MOBILE (Monthly Oral iBandronate In LadiEs), a two-year, randomized, double-blind trial in 1,609 postmenopausal women, show that Bonviva taken orally in a novel, once-a-month form, was at least comparable to the approved once-daily oral Bonviva in increasing spine and hip bone mineral density (BMD)1,2 and reducing bone resorption (bone breakdown)3 and was well tolerated4. In addition, the 150mg Bonviva regimen was prospectively demonstrated to be significantly better than the 2.5mg Bonviva daily regimen.

"These findings are important because they show that Bonviva has potential for once-monthly oral dosing, which may provide a more convenient treatment option for many women with post-menopausal osteoporosis," said lead investigator Robert Recker, M.D., Chief of Endocrinology and Director of the Osteoporosis Research Center at the Creighton University School of Medicine in Omaha, Nebraska. "Less frequent dosing may be less disruptive to patients' morning routines and help them stay on therapy, which is critical since osteoporosis is a chronic disease that requires patients to take medication as prescribed over the long-term to derive the most benefit."

Poor Adherence to Current Bisphosphonates

In addition three new studies were also presented which showed that more than half of women with postmenopausal osteoporosis do not stay on their prescribed bisphosphonate therapy,5,6,7 resulting in smaller gains in bone mineral density and, potentially, an increased risk for fractures compared to women who stay on therapy as directed6,7. This is an increasing concern with data showing that up to 80% of patients who take a once-daily bisphosphonate and up to 60% of patients who take a once-weekly bisphosphonate fail to reach the end of the first year8 (ie discontinue treatment within a year). These new data reinforced that adherence was better with oral weekly rather than with daily-dosed bisphosphonates, but was suboptimal for both dosage forms5,6 with authors concluding that less-frequent dosing regimens, using appropriate doses, show improved benefits.

Commenting on the data, lead investigator Joyce Cramer, associate research scientist, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, said:

"Many patients do not adhere to bisphosphonate therapy, in part because osteoporosis is an asymptomatic, chronic condition. An additional barrier to treatment adherence is that current oral bisphosphonates need to be administered according to strict treatment guidelines, including remaining upright and not eating, drinking (except water) or taking other medications for a period of time after the bisphosphonate therapy is taken. These study findings suggest that a less frequent dosing regimen improves adherence with bisphosphonate therapy. However, adherence with even once-weekly dosing is suboptimal, so alternative dosing regimens should be explored."

Current bisphosphonate therapies are available as daily and weekly dosing formulations. Roche and GlaxoSmithKline are exploring monthly and other less-frequent dosing regimens of the product, which was approved in a daily oral form in the US in May 2003 and in Europe in February 2004. The companies are not marketing the daily formulation, but submitted a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration for a once-monthly oral formulation in May 2004 and a marketing authorization application in Europe in September

2004. Regulatory dossiers for an intravenous formulation are planned to be submitted in the near future.

About MOBILE

The new Bonviva findings were based on data from MOBILE (Monthly Oral iBandronate In LadiEs), a two-year, randomized, double-blind trial comparing the efficacy and safety of monthly oral doses of ibandronate (100mg on a single day; 100mg as separate 50mg doses on two consecutive days; or 150 mg on a single day) versus the oral daily regimen (2.5 mg), approved by the FDA and European Commission, in 1,609 women with postmenopausal osteoporosis. During four presentations, covering different aspects of the results, at the ASBMR Annual Meeting, researchers provided one-year data from MOBILE showing that:

-- All monthly oral regimens were proven non-inferior and the 150mg regimen was prospectively demonstrated to be superior to the daily ibandronate regimen

-- Women taking monthly ibandronate had at least a comparable increase in bone mineral density (BMD) of the lumbar spine (LS) and total hip (TH), and an equal reduction in bone resorption, compared to women who received daily ibandronate; those taking the 150 mg/month dose had the greatest increase in BMD and greatest reduction in bone resorption.

-- Ibandronate was shown to increase LF BMD by 3.9%, 4.3%, 4.1% and 4.9% in the daily 50mg/50mg, 100mg and 150mg arms

-- More patients in the 100mg and 150mg arms achieved substantial increases in LS BMD (>6%) and TH BMD (>3%) than in the daily arm

-- In addition, most participants achieved increases in both LS and TH BMD above baseline (p£0.001 for 100mg and 150mg comparable to 2.5mg)

-- Further, a significantly greater proportion of women in the 150mg per month groups achieved significant increases above baseline in lumbar spine and total hip BMD after one year compared to those in the daily dose group

-- All four ibandronate regimens significantly and similarly suppressed serum levels of serum C-telopeptide crosslinks (sCTX), a biochemical marker of bone turnover

-- Monthly and daily ibandronate rapidly reduced bone resorption to normal levels within three months of initiation, and maintained this suppression with continued therapy

-- A significantly greater proportion of women in the 150 mg/month group achieved pre-defined reductions (greater than 30 percent, 50 percent and 70 percent below baseline levels) in bone resorption compared to those in the daily dose group

-- In all the studies, once-monthly dosing was well tolerated and similar to daily dosing in terms of adverse effects (e.g., upper gastrointestinal disturbances)

About the Persistence Studies

Three studies were presented reviewing adherence to osteoporosis therapy, examining both persistence (staying on a medication) and compliance (taking the medication as directed):

-- One study5 assessing persistence over one year in more than 200,000 US women, 50 years and older, taking either daily (33,767 women) or weekly (177,552 women) bisphosphonate therapy showed only one-third of patients on daily therapy and just less than half (44.8 percent) on weekly therapy had 'persisted' or continued taking their medication for an adequate period of time.

-- Similar findings from another five-year study of 2,741 postmenopausal women newly-prescribed a once-weekly or once-daily bisphosphonate6 showed that weekly bisphosphonate users had better persistence and compliance than daily users, but rates were suboptimal for both dosing regimens.

-- The negative clinical impact of poor adherence was shown in a third presentation7, where data taken over three years on 1,041 patients with osteoporosis showed that consistent users saw their lumbar spine BMD increase significantly from baseline after one, two and three years whereas inconsistent users saw no significant improvement in BMD until the third year, when a modest gain occurred. In addition, there was a trend of a 27 percent greater 10-year fracture risk in inconsistent compared with consistent users.

About Bonviva

-- Bonviva, a potent bisphosphonate, has been studied to date in clinical trials involving over 9,000 patients

-- The ongoing clinical development programme is evaluating monthly oral and bi-monthly/quarterly intravenous dosage regimens in women with postmenopausal osteoporosis

-- Once-daily Bonviva is indicated for the treatment and prevention of osteoporosis in postmenopausal women by reduction of elevated bone turnover, increasing bone mineral density and reduction of the incidence of vertebral fractures

-- Bonviva is the only bisphosphonate that has demonstrated a reduction in vertebral fracture risk using a drugfree interval of more than two months (intermittent arm of BONE)

-- Studies specifically designed to demonstrate reductions in non-vertebral or femoral neck fractures have not been conducted with Bonviva

-- Bonviva, like other bisphosphonates administered orally, may cause upper gastrointestinal disorders such as dysphagia, esophagitis and esophageal or gastric ulcer.

About the Roche/GSK Collaboration

In December 2001, Roche and GSK announced that they would co-develop and co-promote Bonviva for the treatment and prevention of postmenopausal osteoporosis in all countries, except Japan. The Roche/GSK collaboration provides expertise and commitment to bring new osteoporosis therapies to market as quickly as possible.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's leading research-intensive healthcare groups. Its core businesses are pharmaceuticals and diagnostics. As a supplier of innovative products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche is number one in the global diagnostics market, the leading supplier of medicines for cancer and transplantation and a market leader in virology. In 2003, the Pharmaceuticals Division generated 19.8 billion Swiss francs in prescription drug sales, while the Diagnostics Division posted sales of 7.4 billion Swiss francs. Roche employs roughly 65,000 people in 150 countries and has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai.

About GSK

GSK, one of the world's leading research-based pharmaceutical and healthcare companies, is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

All trademarks used or mentioned in this release are legally protected.

References

1 Miller PD, Drezner MK, Delmas PD, Stakkestad JA, Hughes C, Bonvoisin B, Reginster J-Y. Monthly oral ibandronate is at least as effective as oral daily ibandronate in postmenopausal osteoporosis: 1-year results from MOBILE. Poster F408, presented at: 26th Annual Meeting of the American Society for Bone Mineral Research, October 1-5, 2004, Seattle, WA.

2 Emkey R, Felsenberg D, Stepan JJ, Hughes C, Dumont E, Van der Auwera P, Recker RR. Once monthly dosing increases the proportion of patients who respond to oral ibandronate: 1-year results from MOBILE. Poster M432, presented at: 26th Annual Meeting of the American Society for Bone Mineral Research, October 1-5, 2004, Seattle, WA.

3 Recker RR, Kendler DL, Adami S, Hughes C, Dumont E, Schimmer RC, Cooper C. Monthly oral ibandronate significantly reduces bone resorption in postmenopausal osteoporosis: 1-year results from MOBILE. Poster F406, presented at: 26th Annual Meeting of the American Society for Bone Mineral Research, October 1-5, 2004, Seattle, WA.

4 Lewiecki EM, Miller PD, Lorenc R, Hughes C, Bonvoisin B, McClung MR. Monthly oral ibandronate is well tolerated in women with postmenopausal osteoporosis: 1-year results from MOBILE. Poster M429, presented at: 26th Annual Meeting of the American Society for Bone Mineral Research, October 1-5, 2004, Seattle, WA.

5 Recker RR, Gallagher R, Amonkar M, Smith JC, MacCosbe PE. Medication persistence is better with weekly bisphosphonates, but it remains suboptimal. Poster SA407, presented at: 26th Annual Meeting of the American Society for Bone Mineral Research, October 1-5, 2004, Seattle, WA.

6 Cramer JA, Amonkar MM, Hebborn A, Suppapanya. Does dosing regimen impact persistence with bisphosphonate therapy among postmenopausal osteoporotic women. Poster M434, presented at: 26th Annual Meeting of the American Society for Bone Mineral Research, October 1-5, 2004, Seattle, WA.

7 Sebaldt RJ, Shane LG, Pham BZ, Cook RJ, Thabane L, Petrie A, Olszynski WP, Hanley DA, Brown J, Adachi1 JD, Murray T, Josse R, Papaioannou A. Impact of non-compliance and non-persistence with daily bisphosphonates on longer-term effectiveness outcomes in patients with osteoporosis treated in tertiary specialist care. Poster M423, presented at: 26th Annual Meeting of the American Society for Bone Mineral Research, October 1-5, 2004, Seattle, WA.

8 DIN-LINK data, CompuFile Ltd, January 2004. NB: Patients are excluded from the analysis at the point where they stop taking therapy altogether or have failed to comply fully.

For further information contact:

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