RWE studies are performed when any drug is on the market with two main objectives. The first objective is to confirm the efficacy and safety in the normal population of patients, without exclusion criteria seen in Phase II and III trials. The second objective is to collect safety data from a much larger patient population for the possible identification of immediately rare or very rare adverse reactions. Below is a good example of the identification of a rare adverse event thanks to RWE studies. Of note, this rare adverse event was not identified during the pre-NDA clinical trials.

“The U.S. FDA is investigating the risk of severe hypocalcemia with serious outcomes, including hospitalization and death, in patients with advanced kidney disease on dialysis treated with the osteoporosis medicine Prolia (denosumab). Our review of interim results from an ongoing safety study of Prolia suggests an increased risk of hypocalcemia in patients with advanced kidney disease. Preliminary results from a separate internal FDA study further investigating hypocalcemia in dialysis patients treated with Prolia show a substantial risk with serious outcomes, including hospitalization and death.

Because of the frequency and seriousness of these risks, we are alerting healthcare professionals and patients about them and that we are continuing to evaluate this potential safety issue with Prolia use in patients with advanced kidney disease, particularly those on dialysis. We will communicate our final conclusions and recommendations when we have completed our review or have more information to share.

Patients should not stop Prolia treatment without first consulting your healthcare professional, as stopping may worsen your bone condition. Talk to your healthcare professional about any concerns you may have, including possible alternative treatments. Tell your health care professional if you experience any symptoms of low blood calcium levels such as unusual tingling or numbness in the hands, arms, legs, or feet; painful muscle spasms or cramps; voice box or lung spasms causing difficulty breathing; vomiting; seizures; or irregular heart rhythm.

Healthcare professionals should consider the risks of hypocalcemia with the use of Prolia in patients on dialysis. When Prolia is used in these patients, adequate calcium and vitamin D supplementation and frequent blood calcium monitoring, possibly more often than is already being conducted, may help decrease the likelihood or severity of these risks. Advise patients on dialysis to immediately seek help if they experience symptoms of hypocalcemia.”1

Read the full communication here.

References

  1. Center for Drug Evaluation and Research. (2022, December 5). FDA investigating risk of severe hypocalcemia in patients on dialysis receiving osteoporosis medicine Prolia (denosumab). U.S. Food And Drug Administration. https://www.fda.gov/drugs/drug-safety-and-availability/fda-investigating-risk-severe-hypocalcemia-patients-dialysis-receiving-osteoporosis-medicine-prolia

Disclaimers

  • The material in these reviews is from various public open-access sources, meant for educational and informational purposes only
  • Any personal opinions expressed are those of only the author(s) and are not intended to represent the position of any organization(s)
  • No official support by any organization(s) has been provided or should be inferred