Senator Grills FDA Over Handling of REMS for Transmucosal Fentanyl Products
In a letter to US Food and Drug Administration (FDA) Commissioner Scott Gottlieb last week, Sen. Ed Markey (D-MA) questioned the agency's oversight of risk evaluation and mitigation strategies (REMS) for opioids, including transmucosal immediate-release fentanyl (TIRF) products.TIRFs are a highly-potent class of opioids, which include Insys Therapeutics' Subsys (fentanyl sublingual spray) and Galena Biopharma's Abstral (fentanyl sublingual tablets), that are indicated only to treat breakthrough pain in cancer patients who are opioid tolerant.
Since 2011, FDA has required a single, shared REMS for all TIRF products to restrict their distribution and ensure that prescribers have undergone training and certify that they are aware of the risks of prescribing TIRFs off-label.
Sen. Markey's letter comes weeks after a New York Times article, citing documents obtained by researchers at the Johns Hopkins Bloomberg School of Public Health via the Freedom of Information Act, alleged that the agency failed to act despite being aware that patients were being prescribed TIRFs off-label.
The documents include surveys from 2013 and 2017 that found many TIRF prescribers gave the drugs to patients without cancer and that nearly half of patients believed the drugs were approved by FDA for uses outside of treating pain in cancer patients.
Speaking to the Times, Center for Drug Evaluation and Research Director Janet Woodcock said the data available to the agency, which comes from multiple sources, "isn't very good," making it difficult to determine potential harm to patients.
The day after the Times article was published, FDA held an advisory committee meeting looking into potential changes to the REMS for TIRF products.
Letter
In the letter, Sen. Markey expresses concern that manufacturers of risky products are left to manage REMS for those products and asks FDA for information on its oversight of the REMS for TIRF products.
Markey says the information published in the Times article seems to contradict assurances he received in a November 2017 communication from FDA that stated, "there is information that shows compliance with the [REMS] program requirements and that patient and prescriber knowledge of the risks are high."
Specifically, Markey requests that FDA provide him with information from any assessments that led the agency to reach the conclusion they reached in the November 2017 letter and whether the agency believes the elements to ensure safe use (ETASU) for the TIRF REMS program are sufficient.
Markey also asks whether FDA attempted to obtain additional information after receiving the industry surveys that indicated that TIRF drugs were being prescribed off-label, and what FDA does when it receives information that an opioid is being prescribed outside of REMS requirements.
Additionally, Markey questions Woodcock's assertion in the Times article that imposing a more stringent REMS for TIRF products would be "extremely onerous."
"Given that 115 people die each day from an opioid overdose, including an overdose caused by prescription drugs, it is important that the FDA use its full authority to ensure prescription opioids are prescribed as intended, and patients and providers are well aware of the potential risks," Markey writes.
Letter