Xeris Pharmaceuticals Receives First Enforcement Letter of 2023 - “One Off” or Beginning of a New Trend?
With the June 7 release of the first FDA enforcement letter of 2023, I asked Howard Dorfman, Founder of H.L. Dorfman Pharmaceutical Consulting, for his perspective on the letter’s issuance. Howard is an expert in FDA regulatory law, fraud and abuse, compliance programs, and risk management procedures. He is also author of the Practicing Law Institute’s Answer Book on Pharmaceutical Compliance and Enforcement, and a Visiting Distinguished Professor at Seton Hall Law School.
Howard raises important questions about the letter which he says will come to light as FDA shares it’s perspectives on enforcement:
Is the letter a harbinger of increased enforcement activity by OPDP? (See blog on Increased Enforcement)
Can we expect a more aggressive review of promotional claims based on clinical trial data?
Did OPDP consciously choose to utilize an untitled letter rather than a warning letter to make a point?
In any of these cases, it’s critical to understand the FDA regulatory requirements when promoting prescription drugs. Risk minimization, overstatement of efficacy and inappropriate use of clinical data are fundamentally violative in the development of compliance promotional materials
Perspective by Howard Dorfman
On June 13, 2023, the Office of Prescription Drug Promotion (OPDP) Issued an untitled letter to Xeris Pharmaceuticals (“Xeris”), citing the company’s patient website for its drug Recorlev for making false and misleading claims and representations about the safety and efficacy of the drug. This letter represents the first untitled letter issued by OPDP since June 2022.
Given the relative inactivity of OPDP over the last several years in issuing untitled and warning letters, the release of an untitled letter a year after the last one invites greater scrutiny, particularly whether a more active and engaged FDA will be taking a more aggressive enforcement approach moving forward.
Recorlev is a prescription drug indicated for the treatment of a condition in adult patients with Cushing’s syndrome for whom surgery is not an option or has not provided a cure. The approved labeling contains boxed warnings regarding the risks of Hepatoxicity and QT prolongation as well as a contraindication in patients with cirrhosis and other serious liver-related conditions. The product website presented a more limited recitation of the drug’s safety profile, only noting that patient monitoring while on therapy was important and that “Side effects can occur with Recorlev, including some that are serious.”
The FDA and its promotional review and enforcement function through OPDP have taken a consistently hard line when confronted with promotional campaigns that are deemed to have “watered down” the communication of adverse event information generally and the FDA required warning information in particular. This concern has been considered of even greater significance where the information platform is directed to patients and caregivers and not to HCPs who would presumably serve as a learned intermediary and apprise patients of the risks as well as the benefits of a therapeutic option.
One additional takeaway from the Xeris untitled letter is the attention paid to the inappropriate use of the clinical trial data in support of the efficacy claims. OPDP indicated that Xeris inflated the number of subjects who benefitted from Recorlev, including a claim that 52% of patients had normal cortisol levels at the end of the trial but failing to disclose that more than half the subjects had dropped out of the study before the end of the trial due to adverse events or lack of efficacy.
Another problem observed by OPDP arose from the suggestion that 67% of patients who had continued on to the second part of one of the studies had normal cortisol levels by the end of the study. What was not disclosed was that technically that observation was not made at the conclusion of the entire study but only at the end of the titration phase while failing to mention two other phases of the study that had yet to be completed. OPDP has access to the data submitted in support of a drug application as well as the expertise and conclusions of the FDA review division in reviewing efficacy claims; these resources help uncover attempts to misrepresent clinical trial data used to support promotional claims.