Gottlieb Issues Statement On Adverse Event Limitations – An Attempt To Quell Fears?

Commissioner Scott Gottlieb's statement noting the limitations of FAERS comes just four days after he was quoted in an FDA announcement about the launch of a more searchable portal for the adverse event database.

US FDA Commissioner Scott Gottlieb outlined the limitations of data from FDA's Adverse Event Reporting System (FAERS) in what may be an attempt to tamp down reactions to media and analyst reports on adverse events.

In an Oct. 2 statement, Gottlieb stressed that data associated with a particular drug or biologic do not necessarily mean the product is the cause of the adverse event. "Importantly, the FAERS data by themselves are not an indicator of the safety profile of the drug or biologic," Gottlieb said. 'Patients should still talk to their health care professional if they have any concerns regarding their medications."

The timing of the statement is of interest, as it comes just four days after FDA announced the launch of its more user-friendly FAERS search tool that is designed to make it easier for stakeholders to access the information. Previously, only people familiar with the creation of relational databases were able to search the raw data consisting of individual case safety reports.

The search tool allows users to search for and organize data by criteria such as the specific product name, the type of adverse event and a specific timeframes of adverse events.

Gottlieb previously announced the agency was planning to release the improved search tool, noting that clinicians often have difficulty searching for such data. (Also see "US FDA To Publish Own Datasets In Latest Signal Of Enhanced Transparency" - Pink Sheet, 18 Sep, 2017.)

"Tools like the FDA Adverse Event Reporting System are critical to the FDA’s ability to help ensure the greatest level of transparency and help patients and providers make safe use of drug and biologic products after they are approved by the FDA," Gottlieb said in a Sept. 28 statement on the launch of the tool. "The FDA is committed to fully informing patients and providers of adverse events reported with medical products and this enhanced portal now provides patients, doctors and others with easier access to the data they are interested in."

The initial statement also contained language identical to that included in the commissioner's personal statement about the limitations of adverse event data. Recent public reactions to adverse event news, however, may have inspired Gottlieb and the agency to double down to quell public fears about the subject. FDA did not respond to a request for comment on the timing of the statement.

The Case Of Intercept

After the new search tool became available, media and analyst reports about adverse events that hadn't been previously highlighted sent several biotech stocks on roller coaster rides. But perhaps the strongest recent example of impact of FAERS can be seen in the case of Intercept Pharmaceuticals Inc.'s Ocaliva (obeticholic acid). While not participated by the new search tool, the incident illustrates the power that the database has to change the trajectory of products.

FDA warned in a Sept. 21 safety communication of 19 deaths and serious liver injury among patients taking Ocaliva, which was approved in May 2016 in combination with ursodeoxycholic acid for the treatment of primary biliary cholangitis (PBC). Some of the cases were related to excessive dosing of the drug. (Also see "FDA Warning On Ocaliva Puts Intercept's NASH Opportunity In Jeopardy" - Scrip, 22 Sep, 2017.)

Following the release of the safety communication, Intercept's stock dropped 38% from $98.59 to $61.59 over the two-day period that followed. (Also see "FDA Warning On Ocaliva Puts Intercept's NASH Opportunity In Jeopardy" - Scrip, 22 Sep, 2017.) Its stock price sits at $59.55 at the close of business on Oct. 2.

Ocaliva could also have its label changed to include a boxed warning to inform prescribers of appropriate dosing. (Also see "Intercept's Ocaliva Seems Headed For Black Box On Liver Injury Risk" - Pink Sheet, 25 Sep, 2017.) Additionally, a Sept. 22 Laidlaw & Company note there could be tighter restrictions, since some of the patients with adverse events were dosed correctly.

"Additionally, we believe is it noteworthy that the FDA’s Adverse Event Reporting System (FAERS) includes only the cases submitted to them, which means there might be more cases than accounted for," the note states.

In total, 852 adverse events associated with Ocaliva have been reported to the FAERS database, including 114 serious cases and 24 death cases. Although the specific reactions are listed, it is impossible to know their link to the drug just by looking at the search tool. The risk profile of Ocaliva seems likely to change because of the adverse events collected in the database.

Gottlieb's follow-up on the search tool, which didn't discuss any specific products, pointed to the use of the adverse event data more broadly. "FAERS can be a valuable tool but it is just one of many data sets that helps inform the agency of possible problems associated with a product," he added in his Oct. 2 statement.