The regulator concluded that Prolia (denosumab) increases the risk of severe hypocalcemia, which may result in hospitalization and could trigger life-threatening events or even lead to death.
Pictured: Amgen’s office in Tampa, Florida/iStock, JHVEPhoto
The FDA on Friday updated the label of Amgen’s osteoporosis medicine Prolia (denosumab) to include a boxed warning for the risk of hypocalcemia, or severely low calcium levels, when used to treat patients with chronic kidney disease.
According to the regulator, Prolia’s hypocalcemia risk is much higher in chronic kidney disease (CKD) patients who also have mineral and bone disorder (MBD), which could lead to serious harm including hospitalization, various life-threatening events and death. Severe hypocalcemia may come without symptoms or may manifest as confusion, seizures, fainting and uncontrolled muscle spasms, among other signs.
Per the adjusted label, prescribers should first evaluate patients for the presence of CKD-MBD. Patients with this condition who nevertheless require Prolia treatment should be “supervised by a healthcare provider with expertise in the diagnosis and management of CKD-MBD.”
The FDA found that the risk of severe hypocalcemia was highest in patients with advanced CKD, including those who were dependent on dialysis and those with concurrent MBD. The adverse event typically developed within two to 10 weeks after Prolia injection, though its risk peaked at weeks two through five.
Despite these risks, the FDA has told patients to not stop taking Prolia without consulting their doctors, as doing so might aggravate the risk of bone fractures “including in the spine.”
A boxed warning is the FDA’s most serious precautionary signal for drugs. It signals to prescribers that there is “an adverse reaction so serious in proportion to the potential benefit from the drug … that it is essential that it be considered in assessing the risks and benefits of using the drug,” according to an October 2011 guidance document.
These risks include fatal or life-threatening events, or adverse reactions that could result in permanent disability.
In the case of Prolia, a review by the Centers for Medicare and Medicaid Services flagged a “significant increase” in the risk of severe hypocalcemia in patients treated with Amgen’s drug versus other bisphosphonate-based osteoporosis therapies. The FDA’s Adverse Event Report System also identified 25 cases of severe hypocalcemia from July 2010 through May 2021.
An Amgen spokesperson In a statement to Fierce Pharma said that safety is of the “utmost importance” to the company and that it remains “confident” in the benefit/risk profile of Prolia.
A monoclonal antibody, Prolia binds and blocks the RANK protein which in turn suppresses the action of osteoclasts, bone cells that normally degrade bone to promote repair and remodeling. In many bone diseases, like osteoporosis, osteoclasts often play a pathologic role.
Prolia was first approved in 2010 for postmenopausal women with osteoporosis who are at a high risk of fracture. The therapy has since been approved for other indications, such as improving bone mass in men with osteoporosis, including those undergoing androgen deprivation therapy.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
