Romosozumab Phase 2 data published In New England Journal Of Medicine show significant increases in bone mineral density at both spine and hip

Amgen (NASDAQ:AMGN) and UCB (Euronext Brussels:UCB) today announced results from a Phase 2 trial evaluating romosozumab (AMG 785/CDP7851) in postmenopausal women with low bone mineral density (BMD). Published in the New England Journal of Medicine (NEJM), the trial demonstrated that, compared with placebo, romosozumab treatment for 12 months significantly increased BMD at the lumbar spine, total hip and femoral neck. Significant increases were also observed in the first BMD assessment at three months. Moreover, in exploratory analyses, increases observed at the lumbar spine and hip were significantly greater than those observed with current treatments FOSAMAX® (alendronate sodium) and FORTEO™/FORSTEO® (teriparatide).¹“The results of the study demonstrate significantly increased BMD and stimulation of bone formation with romosozumab treatment in women with postmenopausal osteoporosis,” said Michael McClung, M.D., director of the Oregon Osteoporosis Center and lead study investigator. “Additionally, romosozumab treatment resulted in greater increases in bone mineral density than those seen with both placebo and the active comparators. These data provide important insight into this medicine being developed for women with postmenopausal osteoporosis at high risk for fractures.”

Romosozumab is an investigational medicine in Phase 3 clinical development for the treatment of osteoporosis in postmenopausal women and is not currently approved by any regulatory authority.

In this Phase 2 trial, each of the five romosozumab dose regimens significantly increased BMD compared with pooled placebo groups at the lumbar spine, total hip and femoral neck regions (all p<0.001). The largest increases were observed with the romosozumab 210 mg once-monthly dose, with mean increases compared with baseline of 11.3 percent at the lumbar spine, 4.1 percent at the total hip and 3.7 percent at the femoral neck.

Additionally, in exploratory analyses, BMD gains were significantly greater than active comparators at month 12, with romosozumab treatment achieving a mean increase of 11.3 percent at the lumbar spine compared to increases of 4.1 percent and 7.1 percent at the same region achieved with FOSAMAX and FORTEO, respectively. At the total hip, romosozumab treatment increased BMD 4.1 percent, while observed gains with FOSAMAX were 1.9 percent and with FORTEO were 1.3 percent (all p<0.001).¹

The comparators to romosozumab were placebo, oral FOSAMAX (70 mg weekly) and subcutaneous FORTEO (20 μg daily), both of which were open-label.¹

Adverse events were similar across groups, except for mild, generally non-recurring injection site reactions observed more frequently with romosozumab compared to placebo, but with no observed dose-related relationship. Most common adverse events included mild upper respiratory tract infection, pain in the back and joints, and headache. These reactions did not lead to study drug discontinuation or study withdrawal; the safety of romosozumab will be further addressed in subsequent larger studies.¹

“There remains a significant need for additional treatment options that form new bone. Romosozumab is designed to stimulate bone formation, which makes it different from most available treatments that reduce bone resorption,” said Prof. Dr. Iris Loew-Friedrich, chief medical officer, UCB. “We are encouraged by the emerging efficacy and safety profile, and look forward to further investigating its potential in the ongoing global Phase 3 clinical program.”

“Broken bones due to osteoporosis are common and can have a significant impact on the patient, her family and the healthcare system, yet the seriousness of this health event remains underappreciated, with only two-in-10 women receiving follow-up testing or treatment after they have broken a bone,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “With its bone-forming ability, romosozumab may result in new treatment strategies to help manage this disease.”

Study Design

The study was a Phase 2, multicenter, international, randomized, placebo-controlled, parallel-group, eight-arm study of 419 postmenopausal women aged 55 to 85 years with BMD T-score <–2.0 at the lumbar spine, total hip or femoral neck and >–3.5 at all three sites. Study participants were randomly assigned to receive subcutaneous romosozumab monthly (70, 140, or 210 mg) or every three months (140 or 210 mg), subcutaneous placebo, or oral FOSAMAX (70 mg weekly) or subcutaneous FORTEO (20 μg daily), both of which were open-label.¹

The primary endpoint was percentage change from baseline in lumbar spine BMD at 12 months. Secondary endpoints included percentage changes in BMD and in bone turnover markers at other sites.¹

About Osteoporosis

Osteoporosis affects many women after menopause2,3 as their ability to form new bone cannot counter balance the rate at which bone is being removed. This bone loss leads to weakened bones over time, increasing the potential for a break.^4,5

About half of all women over age 50 will have an osteoporosis-related fracture in their remaining lifetime.⁶ Only 24 percent of women who suffered an osteoporotic fracture received treatment during the following year.^7*

According to the National Osteoporosis Foundation, those who have sustained a hip fracture are at a four-times greater risk of a second hip fracture.⁶

The World Health Organization has officially declared osteoporosis a public health crisis, while the International Osteoporosis Foundation urges governments worldwide to make osteoporosis a healthcare priority.

About Romosozumab

Romosozumab is an investigational bone-forming agent. By inhibiting the protein sclerostin, romosozumab is designed to increase bone formation and decrease bone breakdown.^8,9,10 Romosozumab is being studied for its potential to reduce fracture risk in an extensive global Phase 3 program. This program includes two pivotal studies evaluating romosozumab against both placebo and active comparator in more than 10,000 patients with osteoporosis. Romosozumab is being co-developed by Amgen and UCB.

References

1. McClung MR, Grauer A, Boonen S, et al. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. DOI: 10.1056/NEJMoa1305224.
2. U.S. Department of Health and Human Services, Office of the Surgeon General. The 2004 Surgeon General’s Report on Bone Health and Osteoporosis: What It Means to You. http://www.surgeongeneral.gov/library/reports/bonehealth/OsteoBrochure1mar05.pdf. Published October 14, 2004. Accessed November 18, 2013.
3. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. http://nof.org/files/nof/public/content/file/344/upload/159.pdf. Published January 2010. Accessed November 18, 2013.
4. Chavassieux P, et al. Insights into material and structural basis of bone fragility from diseases associated with fractures: how determinants of the biomechanical properties of bone are compromised by disease. Endocr Rev. 2007;28:151-164.
5. Seeman E, Delmas PD. Bone quality – the material and structural basis of bone strength and fragility. N Engl J Med. 2006;354:2250-2261.
6. National Osteoporosis Foundation. Fast Facts. http://old.nof.artsmithclients.com/node/40. Accessed November 18, 2013.
7. Andrade SE, et al. Low frequency of treatment of osteoporosis among postmenopausal women following a fracture. Arch Intern Med. 2003;163:2052-2057.
8. Padhi D, et al. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011;36(1):19-26.
9. Li X, et al. Sclerostin antibody treatment increases bone formation, bone mass and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. 2009;24:578-588.
10. Ominsky MS, et al. Inhibition of sclerostin by monoclonal antibody enhances bone healing and improves bone density and strength of non-fractured bones. J Bone Miner Res. 2011;26:1012-1021.

*Fracture sites: hip, vertebrae or wrist. Data are drawn from a retrospective database study from seven health maintenance organizations.