THOUSAND OAKS, Calif., and BRUSSELS, Belgium—Amgen and UCB Group announced March 20 that in the pivotal Phase 3 BRIDGE trial of men with osteoporosis, their drug romosozumab met the primary endpoint, demonstrating a statistically significant increase in bone mineral density (BMD) at the lumbar spine (as assessed by dual energy x-ray absorptiometry) in men with osteoporosis treated with romosozumab compared with placebo at 12 months.
All secondary endpoints comparing romosozumab with placebo were also met—specifically, patients receiving romosozumab experienced a statistically significant increase in BMD at the femoral neck and total hip at 12 months and a statistically significant increase in BMD at the lumbar spine, femoral neck and total hip at six months, compared with those receiving placebo.
The incidence of adverse events and serious adverse events overall was more or less balanced between the romosozumab and placebo arms of the trial.
“While the focus of managing osteoporosis is often on women, osteoporosis in men is also a serious health issue that poses a significant health risk to millions of men worldwide,” said Dr. Sean E. Harper, executive vice president of research and development at Amgen. “We are excited that these data showed romosozumab stimulates bone formation, leading to increases in bone mass, in this often overlooked and undertreated patient population.”
“Although there has been considerable progress in the treatment and management of osteoporosis, a large unmet medical need remains. One in three women and one in five men over the age of 50 will experience an osteoporosis-related fracture in their lives,” added Dr. Iris Loew-Friedrich, chief medical officer and executive vice president of UCB. “These positive results from BRIDGE add to our growing body of Phase 3 data demonstrating romosozumab’s potential to build bone strength and to decrease fracture risk and thus help fill an unmet need for patients with osteoporosis.”
Now, this good news about primary and secondary endpoints for romosozumab comes off news a little less than a month earlier from the companies that in the Phase 3 FRAME trial for women with osteoporosis, the drug its primary endpoints but not all of its secondary ones.
Specifically, it achieved the co-primary endpoints of reducing the incidence of new vertebral fracture through 12 months and 24 months in postmenopausal women with osteoporosis. Romosozumab also met the secondary endpoint of reducing the incidence of clinical fractures in postmenopausal women with osteoporosis through 12 months.
Where the drug fell short in FRAME, however, was that it didn’t achieve the secondary endpoint of reducing the incidence of non-vertebral fractures through months 12 and 24.
Writing an analysis for the Motley Fool website, Sean Williams played off the arrival of baseball season to suggest the two companies might have “wiffed at the plate” with a drug that had been predicted as being capable of $1 billion or more in annual sales.
As he wrote, “Eli Lilly’s Forteo and Radius’ abaloparatide (assuming approval) are once-daily injectable therapies. By comparison, Amgen’s and UCB’s romosozumab holds the convenience ‘holy grail’ of being a once-monthly injectable solution. If romosozumab demonstrated superiority over the placebo in both primary and secondary endpoints, it would likely be the clear leader in treating osteoporosis among postmenopausal women. But romosozumab’s failure to meet statistical significance in non-vertebral fractures now casts some degree of doubt over its future.”
Williams acknowledges that the drug’s convenience and possibly lower pricing, though, mean the FRAME results weren’t a total strike-out.
And on these points, Zacks Investment Research’s Arpita Dutt substantially agreed, writing in part in a Feb. 23 analyst note:
“Romosozumab, if approved, should complement Amgen’s Prolia which brought in sales of $1.3 billion in 2015 ... But while romosozumab is considered to have blockbuster potential, concerns remain that the recently presented data falls short of data on Radius Health Inc.’s abaloparatide-SC, a daily self-administered injection being evaluated for the treatment of patients with postmenopausal osteoporosis at high risk of fracture.”
“Radius had presented late-stage data on its candidate in Dec 2014 showing that abaloparatide-SC reduced incident vertebral fractures by 86 percent compared to placebo. Radius’ shares shot up more than 25 percent on the romosozumab data—the company plans to file for FDA approval by the end of this quarter,” she added. “However, romosozumab could well have an edge over abaloparatide-SC given its once-monthly dosing regimen.”
And to wrap it all up, for those who like to know the awkward trial names from with the tidy acronyms are derived, BRIDGE stands for placeBo-contRolled study evaluatIng the efficacy anD safety of romosozumab in treatinG mEn with osteoporosis, while FRAME comes from placebo-controlled FRActure study in postmenopausal woMen with ostEoporosis.
