Amgen, UCB's osteoporosis drug Evenity linked with higher rate of serious cardiovascular events: study

Amgen and UCB announced that in a Phase III study, the experimental drug Evenity (romosozumab) was associated with a higher rate of serious cardiovascular events versus Merck & Co.'s Fosamax (alendronate) in postmenopausal women with osteoporosis at high risk for fracture. Sean Harper, executive vice president of R&D at Amgen, remarked "the newly observed cardiovascular safety signal will have to be assessed as part of the overall benefit:risk profile for Evenity."

The ARCH study randomised 4093 postmenopausal women with osteoporosis at high risk for fracture based on previous fracture history to receive Evenity subcutaneously every month or Fosamax orally every week for 12 months. After the double-blind, active-comparator period, patients received Fosamax for at least a further 12 months. The trial was designed to determine if treatment with Evenity is effective in reducing the incidence of clinical fracture and new vertebral fracture.

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Amgen and UCB noted that the study met both its primary endpoints and the key secondary goal, with results demonstrating that at the primary analysis, treatment with Evenity followed by Fosamax significantly reduced the incidence of new vertebral fractures through 24 months, clinical fractures and non-vertebral fractures compared to alendronate alone. Specifically, women in the Evenity treatment group experienced a significant 50 percent reduction in the relative risk of a new vertebral fracture compared to those receiving Fosamax alone. Further, women taking Evenity had a significant 27-percent reduction in the relative risk of clinical fracture, while non-vertebral fractures were significantly reduced by 19 percent in those given Amgen and UCB's drug, including a "nominally significant" reduction in hip fractures.

However, the companies said that "an imbalance in positively adjudicated cardiovascular serious adverse events was observed as a new safety signal" in the study, with rates of 2.5 percent for Evenity compared to 1.9 percent for Fosamax at 12 months. Iris Loew-Friedrich, UCB's chief medical officer, commented "we are working on understanding the observed cardiovascular safety signal and will continue to discuss these results with global regulators and experts in the field." Shares in UCB fell more than 14 percent on the news.

Regulatory submissions for Evenity based on data from the Phase III FRAME study are currently under review by the FDA, Health Canada and the Pharmaceuticals and Medical Devices Agency in Japan. Amgen and UCB reported last year that the FRAME trial, which enrolled postmenopausal women with osteoporosis, met all of its primary endpoints by reducing the incidence of new vertebral fractures through months 12 and 24.

Amgen indicated Monday that prior to its submission to the FDA, the company agreed with the agency that the ARCH data should be considered in the regulatory review, adding that as a result it "does not expect approval of Evenity in the US to occur in 2017." The drugmakers noted that "engagement" with regulators in Canada and Japan will occur as part of the ongoing review process, while preparations for a marketing submission in Europe will continue as planned.

Although Amgen and UCB did not disclose further details about the serious cardiovascular events, Leerink analyst Geoffrey Porges said he believed Evenity now had only a 50/50 probability of approval. Meanwhile, ISI Evercore analyst Umer Raffat called the ARCH study data "clearly negative and very surprising," adding that he was removing all sales of the drug from his Amgen forecast models. Analysts had previously estimated that Evenity could generate annual sales of about $720 million by 2023.

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