The United States Food and Drug Administration (FDA) Office of Prescription Drug Promotion (OPDP) recently sent its first untitled letter in over a year to Xeris Pharmaceuticals, Inc. for its promotion of its drug Recorlev. OPDP reviewed several branded drug webpages that “make false or misleading claims and representations about the safety and efficacy of Recorlev.”
Recorlev is indicated to treat endogenous hypercortisolemia in adults with Cushing disease that are not eligible for surgery – or patients who have had surgery, but it was not curative. The drug blocks cortisol and testosterone to help Cushing disease patients manage their disease and comes with “serious and potentially life-threatening risks,” including boxed warnings.
The two boxed warnings on the drug outline the risks of hepatotoxicity and QT prolongation. In addition to the boxed warnings, Recorlev is contraindicated in more than a dozen uses, including patients with cirrhosis, recurrent symptomatic cholelithiasis, and patients that are taking drugs that cause QT prolongation associated with ventricular arrhythmias.
One issue OPDP had was that while Xeris said that “side effects can occur with Recorlev, including some that are serious,” it did not mention the drug’s boxed warnings or the specific side effects that are associated with the drug – including the potentially fatal side effects. In fact, OPDP notes that the prescribing information says that 13% of patients taking the drug experienced drug-induced liver injury and that some of the adverse reactions listed on the label occurred in more than 20% of patients, including nausea/vomiting, hypokalemia, insomnia/sleep disturbance, and systemic hypertension.
Additionally, OPDP noted that on one of the website pages, Xeris claimed that “67% of patients who moved on to the second part of the [SONICS] study had normal cortisol levels by the end of the study,” but that statement “misleadingly overstates the efficacy of Recorlev,” as the clinical data from the company shows actual levels are around half of that figure.
The SONICS study consisted of three phases: dose titration, maintenance, and extended evaluation. The 67% figure represents the percentage of patients who had normal cortisol levels at the end of the titration phase of the study. Out of the 94 patients who enrolled in the study and entered the dose titration phase, 77 moved onto the second part of the study. At the end of the maintenance phase, only 29 had normal cortisol levels (38%). By the end of the extended evaluation phase, only 16 had normal cortisol levels (21%). The SONICS study had 51% of patients discontinue their treatment prematurely due to adverse reaction, lack of efficacy, or other reasons. Therefore, OPDP believes that “these results should be interpreted with caution” as the omission of information “undermines the ability of a reader to understand and evaluate the study results presented and thereby creates a misleading impression about the drug’s efficacy.”
The other issue was OPDP felt that the webpages were false or misleading related to risk. While the webpages mentioned “monitoring by your doctor is important so they know how you’re doing” and “heart and liver tests before and during treatment with Recorlev will help your doctor avoid side effects,” these statements “minimize the serious and significant risks associated with the use of Recorlev.” OPDP felt that the “presentation suggests that heart and liver tests alone will enable patients to ‘avoid’ side effects altogether.”
The agency found that these violations were “especially concerning from a public health perspective because the promotional communications create a misleading impression regarding the safety and effectiveness of Recorlev.”
Xeris was given fifteen working days to tell OPDP how it plans to resolve these issues pointed out in the untitled letter.