FDA slaps boxed warning on Amgen's osteoporosis drug Prolia

Use of Amgen’s osteoporosis drug Prolia by those with advanced chronic kidney disease (CKD) can increase the risk of calcium loss in the blood, according to the FDA.

The U.S. regulator has added a new boxed warning for the blockbuster treatment, which has been on the market for 14 years and loses patent protection next year.

Use of Prolia, which is injected every six months, can increase the risk of “severe” hypocalcemia, which is an abnormally low level of calcium in the blood. It's a dangerous but treatable condition that can cause neurologic or psychologic issues that can be fatal.

Severe hypocalcemia can be asymptomatic or may cause confusion, seizures, irregular heart rhythm, fainting, face twitching, uncontrolled muscle spasms, tingling or numbness, the FDA warned.

The new warning follows a safety alert issued by the FDA in November of 2022. That alert was based on interim results from a study that indicated a “substantial risk” of hypocalcemia for people on dialysis.

In a statement, Amgen said “patient safety is of the utmost importance” to the company.

“Approximately 3% of treatment naïve Prolia patients with a known level of CKD are classified as having advanced CKD,” Amgen added. “We remain confident in Prolia and its overall benefit/risk profile.”

Calcium loss has long been a concern for CKD patients, especially those on dialysis. A new evaluation by the FDA—based on data from the Centers of Medicare and Medicaid Services (CMC)—showed a significant increase in patients on Prolia developing hypocalcemia compared to those on more commonly used oral biophosphonates such as Merck’s Fosamax.

During the first 12 weeks of treatment, 41% of those on Prolia developed hypocalcemia, compared with 2% of those on biophosphonates. The greatest risk occurs in the first two to five weeks of administration, according to the FDA.

Patients on Prolia should not quit using the drug without consulting their healthcare provider, the FDA said. The regulator also advised doctors to carefully select patients for the medicine.

Patients also should be monitored closely, particularly in weeks 2 to 10 after each injection, and they may require calcium and vitamin D supplements.

Prolia was initially approved in 2010 for postmenopausal women. Two years later, it was endorsed for men. Sales have steadily increased by double-digit margins, reaching $3.6 billion in 2022. In the second quarter of last year, the medicine's sales reached $1 billion in a quarter for the first time.  

Amgen has built a huge osteoporosis franchise that also includes Xvega and Evenity. In 2022, those drugs combined for sales of $2.8 billion.