Osteoporosis Drug Romosozumab Gains First Approval, in Japan


January 09, 2019

The osteoporosis drug romosozumab (Amgen/Astellas BioPharma) has been approved in its first market worldwide, in Japan, for the treatment of osteoporosis in women at high risk of fracture, where it will be known as Evenity, the companies have announced.

This approval is significant because approval of the agent has been held up in the United States because of safety concerns following the ARCH study, which reported a higher rate of serious adverse cardiovascular events with the drug compared with the bisphosphonate alendronate in May 2017.

The US Food and Drug Administration (FDA) subsequently rejected romosozumab, in July 2017, requesting more data from the ARCH study, in addition to results from the BRIDGE trial, which evaluated romosozumab in men with osteoporosis.

Then, in September 2017, the ARCH study was published in the New England Journal of Medicine, as reported by Medscape Medical News. At the time, physicians said it wasn't clear how romosozumab could be causing the cardiovascular side effects seen in ARCH, although an accompanying editorial noted, "The cardiovascular signal for romosozumab is particularly troubling."

Amgen says the new Japanese approval of romosozumab is based on results from two pivotal Phase 3 studies: FRAME, which included 7180 postmenopausal women with osteoporosis, and BRIDGE, which included 245 men with osteoporosis.

And "the Japanese Pharmaceuticals and Medical Devices Agency undertook a thorough review of the safety profile of [romosozumab], including the cardiovascular safety findings in the ARCH trial."

New Anabolic Agents, FDA's Ad Com Soon to Consider Romosozumab

Romosozumab is an investigational humanized monoclonal antibody that inhibits sclerosin, giving it a unique mechanism of action among osteoporosis agents. Injected subcutaneously, it rapidly increases bone formation and reduces bone resorption simultaneously, increases bone mineral density, and reduces the risk of fracture.

Romosozumab has been a highly anticipated addition to the field of new anabolic drugs for osteoporosis, which includes abaloparatide (Tymlos, Radius Health), authorized by the FDA in April 2017 — the first new osteoporosis agent approved in the United States for 15 years. Abaloparatide was, however, subsequently rejected by the European Medicines Agency in March of last year.

"None of the currently available agents allow you to reduce fractures to the magnitude that these new [anabolic] drugs do," Bart L. Clarke, MD, president-elect of the American Society for Bone and Mineral Research, who is an endocrinologist and associate professor of medicine at the Mayo Clinic, Rochester, Minnesota, told Medscape Medical News in September 2017. "For a treatment for osteoporosis, these drugs are significant and represent a big advance, we think."

In Japan, Toshio Matsumoto, MD, PhD, professor emeritus, Tokushima University, and the advisor of the university's Fuji Memorial Institute of Medical Sciences, said: "Patients with a prior fracture face the risk of having another fracture and particularly stand to benefit from the option of a new bone-forming agent." 

"Physicians have been waiting for a new therapeutic option. I have great hope that the approval of Evenity will help reduce the fracture risk for patients in Japan," he commented in the company press release.

The picture for the drug in the United States will soon become clearer as the FDA's Bone, Reproductive and Urologic Drugs Advisory Committee is due to discuss the biologics license application for romosozumab on January 16.

Follow Lisa Nainggolan on Twitter: @lisanainggolan1. For more diabetes and endocrinology news, follow us on Twitter and on Facebook.


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