US regulators removed a special safety program intended to monitor for certain heart risks with vandetanib (Caprelsa), a drug first approved in 2011 to treat medullary thyroid cancer in patients whose disease has spread or cannot be surgically removed.

The end of the Risk Evaluation and Mitigation Strategies (REMS) program means clinicians will no longer need special certification or extra monitoring beyond standard clinical care when prescribing vandetanib, the US FDA said Thursday.

The FDA used the REMS program for two purposes: to ensure the safety of patients taking vandetanib and to study whether signals about heart risk seen in testing would pose risk to patients.

More Than a Decade of Monitoring

In more than a decade of oversight, REMS assessments reported no cases of torsades de pointes or unexplained sudden deaths among US patients taking Caprelsa, the FDA said. No concerning patterns of heart rhythm problems have emerged, the agency said.

“Cancer specialists now have adequate knowledge about managing the heart rhythm related risks of this medication,” Richard Pazdur, MD, director of the FDA Oncology Center of Excellence said in a press release. “Healthcare providers have incorporated proper safety monitoring into their standard practice, making the formal requirements unnecessary. The mandatory monitoring program has achieved its goals.”

AstraZeneca initially brought vandetanib to the US market. Sanofi acquired vandetanib through its subsidiary Genzyme in 2015.

FDA documents show that Sanofi’s Genzyme unit asked for an end to the REMS program in March.

The FDA said it granted this based on information gathered about the use of vandetanib in practice. For example, survey results indicated that prescriber respondents “were adequately educated about monitoring and managing the risk of QT prolongation,” wrote Shan M. Pradhan, MD, associate director for safety in the Office of Oncologic Diseases at FDA’s Center for Drug Evaluation and Research in September 23 letter to Genzyme.

In addition, several clinical decision support tools and educational resources are available to prescribers.

“Based on the totality of the evidence, knowledge of the risks and appropriate management of those risks have been incorporated into the standard of care for Caprelsa,” Pradhan wrote.

Early Questions

While considering the initial approval of vandetanib, the FDA publicly wrestled with questions about the drug’s cardiac risk. Data from clinical trials suggested the drug could prolong the QT interval and lead to cases of torsades de pointes.

The FDA convened a meeting of the Oncologic Drugs Advisory Committee (ODAC) in December 2010 to offer feedback on ways to use what seemed to be a promising cancer medicine safely. While not asked to vote directly on a question about whether the FDA should approve vandetanib, the panelists were largely supportive of the drug.

“This drug appears to work and appears to work pretty well,” said ODAC member Mikkael A. Sekeres, MD, MS, during the 2010 meeting, while also supporting continued study of the medicine after approval.

In an interview with Medscape Medical News on Thursday, Sekeres, now chief of the division of hematology at University of Miami Sylvester Cancer Center, Miami, said the FDA’s approach on vandetanib showed an appropriate balancing of risk and benefit.

Vandetanib was an example of a drug that could help “a population of patients with cancer who desperately needed a new therapy” but had side effects associated with it, he said.

“So, the FDA did the right thing,” Sekeres said. “They approved the drug for marketing purposes to make it available to those people and required that it be part of a program where safety would be closely monitored.”

“After monitoring that safety for a decade, the FDA did the right thing again,” Sekeres added. “After determining that the drug did not result in excess rates of torsades de pointes, the FDA removed the requirement for the extra level of safety.”

Sekeres reported having no relevant financial disclosures. 

Kerry Dooley Young is a freelance journalist based in Washington, DC. She has covered medical research and healthcare policy for more than 20 years.