Amgen and UCB have acknowledged that their Biologics License Application (BLA) for Evenity™ (romosozumab) has been rejected by the FDA.
The companies said yesterday that they received a Complete Response Letter asking them to include in their application efficacy and safety data from the Phase III ARCH (Active-contRolled fraCture study in postmenopausal women with osteoporosis at High risk of fracture) trial, which compared Evenity to Merck’s Fosamax® (alendronate sodium).
In announcing topline data from ARCH on May 21, Amgen and UCB disclosed a higher risk of cardiovascular serious adverse events with Evenity compared with Fosamax—2.5% for those treated with Evenity versus 1.9% treated with Fosamax at 12 months.
Amgen and UCB added that Evenity met its primary and key secondary endpoints in ARCH. The companies said treatment with the sclerostin-targeting monoclonal antibody (mAb) for 12 months followed by alendronate significantly reduced the incidence of new vertebral fractures through 24 months, as well as clinical fractures and nonvertebral fractures in postmenopausal women with osteoporosis at high risk for fracture, compared to alendronate alone.
In yesterday’s statement, an Amgen executive restated that an FDA rejection for Evenity was expected based on the cardiovascular risk data from ARCH—something Amgen and UCB said in May.
“During our interactions with the FDA, we agreed that the ARCH data should be considered in the regulatory review prior to the initial marketing authorization and, as a result, anticipated this request. We look forward to working through the review process with the Agency,” said Sean E. Harper, M.D., evp of R&D at Amgen. “We remain committed to helping patients with osteoporosis and will use the additional time to better understand the benefit:risk profile of Evenity.”
The Amgen–UCB cardiovascular risk setback came less than a month after the osteoposis treatment of rival Radius Health, Tymlos™ (abaloparatide) injection, was approved by the FDA. Radius said on April 28 that the FDA approved Tymlos for postmenopausal women with osteoporosis at high risk for fracture defined as history of osteoporotic fracture, multiple risk factors for fracture, or patients who have failed or are intolerant to other available osteoporosis therapy.
Today, however, Radius announced the appointment of a new president and CEO. Jesper Høiland, previously the president of Novo Nordisk Inc. USA, who was named to succeed Robert Ward, with no explanation provided for the change in a company statement. Ward had held the position since 2013 and steered the company through obtaining regulatory approval for Tymlos as well as raising more than $750 million in private and public financings, including the company’s 2014 IPO.
Data from 3 Trials Planned
Pascale Richetta, M.D., head of bone disorders patient value unit and evp with UCB, added that the companies will also add in their resubmitted BLA for Evenity data from a third Phase III trial, BRIDGE, assessing their candidate in men with osteoporosis, in addition to the data from ARCH and FRAME.
“With all three pivotal romosozumab Phase III studies now included in the clinical evidence package, representing data from more than 11,000 patients, we are committed to bringing this important potential new treatment to those people living at risk of fragility fractures,” Dr. Richetta stated.
BRIDGE (placeBo-contRolled study evaluatIng the efficacy anD safety of romosozumab in treatinG mEn with osteoporosis) is a randomized, double-blind, placebo-controlled study of 245 men aged 55–90 years with osteoporosis and a history of fragility fracture (excluding hip fracture) or vertebral fracture. The study evaluated the effectiveness of Evenity treatment for 12 months, compared with placebo, in increasing bone mineral density (BMD) at the lumbar spine, and the effect on BMD at the femoral neck and total hip.
ARCH is a randomized, double-blind, alendronate-controlled study of Evenity in 4093 postmenopausal women with osteoporosis at high risk for fracture based on previous fracture history. The study evaluated 12 months of Evenity treatment (210 mg), followed by at least 12 months of alendronate treatment (70 mg), compared with alendronate treatment alone, to determine effectiveness in reducing the incidence of clinical fracture (nonvertebral fracture and clinical vertebral fracture) and new vertebral fracture.
The Amgen-UCB BLA had been supported by data from FRAME, a Phase III study assessing Evenity in 7180 postmenopausal women with osteoporosis. FRAME compared Evenity with placebo in reducing the risk of new vertebral fractures through to 12 months, and then compared Evenity treatment for 12 months followed by denosumab therapy for 12 months, compared with placebo then denosumab therapy.
Evenity has been developed by Amgen and UCB as part of a long-term collaboration and license agreement signed in 2004 to develop antibody products targeting sclerostin.