Romosozumab was originally discovered by Celltech (now owned by UCB). Celltech entered in a partnership with Amgen in 2002 for the product’s development. As of January 2014, Phase 3 clinical trials are recruiting patients.
- “Statement On A Nonproprietary Name Adopted By The USAN Council: Romosozumab”. American Medical Association.
- Osteocyte control of bone formation via sclerostin, a novel BMP antagonist. EMBO J. 2003 Dec 1;22(23):6267-76.
- Celltech group Annual Report and Accounts 2002
- ClinicalTrials.gov: Romosozumab
Sclerostin / Source: Wikimedia Commons and JMROL
Biloine Young • Thu, November 1st, 2012
Good news for postmenopausal women came from a report given by Michael R. McClung, M.D., at the annual meeting of the American Society for Bone and Mineral Research. McClung and colleagues have found an antibody that targets the Wnt signaling pathway and its osteocyte-regulating molecule sclerostin, which increases bone formation while decreasing bone resorption, according to Nancy Walsh, staff writer for MedPage Today.
Walsh reports that one year of treatment with the antibody romosozumab (formerly AMG 785) led to an 11.3% absolute increase in bone mineral density (BMD) in postmenopausal women with low BMD (body mass index). That compared with BMD increases of only 7% with teriparatide (Forteo), 4% with alendronate (Fosamax), and no change with a placebo. “The discovery of sclerostin as an osteocyte-mediated stimulator of osteoblast function and bone formation opened the door for considering the inhibition of this protein and regulator as a target for osteoporosis treatment,” McClung said.
To further explore the therapeutic potential of this antibody, the researchers conducted a Phase II study that enrolled 419 women whose lumbar spine, total hip, or femoral neck T-scores were between −2 and −3.5. The mean age of the participating women was 67. Researchers randomized participants to receive romosozumab in dosages of 70 mg, 140 mg, or 210 mg each month, 140 or 210 mg every three months, or a placebo.
The total hip increase in BMD with romosozumab was 4.1% at 12 months, which was approximately double that seen with alendronate and teriparatide. The researchers also saw changes in biomarkers of bone metabolism, McClung noted. The pattern seen with romosozumab, McClung said, was increases for serum P1NP, favoring bone formation, and decreases in serum CTX, suggesting a slowing of bone resorption after one week of treatment.
Adverse events were similar in the treatment groups. The most common was back or extremity pain. Serious adverse events occurred in 9.8% of the romosozumab groups and in 14% of the placebo group. The only treatment-related adverse events that occurred in the romosozumab groups were injection site reactions, but these were mild and did not lead to a discontinuation of treatment, said McClung.
Amgen/UCB osteoporosis drug shines in Phase II
Amgen and UCB have been boosted by promising mid-stage data for their investigational osteoporosis drug romosozumab.
A Phase II trial, the results from which have been published in the New England Journal of Medicine,showed that romosozumab demonstrated a significant increase in bone mineral density. Specifically, the trial demonstrated that, compared with placebo, treatment for 12 months with the anti-sclerostin biologic significantly increased BMD at the lumbar spine, total hip and femoral neck.
Amgen and UCB noted that significant increases were also observed in the first BMD assessment at three months and moreover, in exploratory analyses, increases observed at the lumbar spine and hip “were significantly greater than those observed with current treatments”, namely Merck & Co’s Fosamax (alendronate) and Eli Lilly’s Forteo (teriparatide).
Iris Loew-Friedrich, chief medical officer at UCB, noted that romosozumab is designed to stimulate bone formation, “which makes it different from most available treatments that reduce bone resorption”. She added that “we are encouraged by the emerging efficacy and safety profile, and look forward to further investigating its potential in the ongoing global Phase III clinical programme”. Final data from the latter, which will enroll up to 10,000 patients, are expected by the end of 2015.
Sean Harper, Amgen R&D chief, noted that broken bones due to osteoporosis are common “yet the seriousness of this health event remains underappreciated, with only two in ten women receiving follow-up testing or treatment after they have broken a bone”. He added that “with its bone-forming ability, romosozumab may result in new treatment strategies”.
If all goes well in Phase III, many observers believe romosozumab could be a blockbuster.
DR ANTHONY MELVIN CRASTO Ph.D