OPDP hands first untitled letter in twelve months to Xeris

The US Food and Drug Administration’s (FDA) Office of Prescription Drug Promotion (OPDP) broke its year-long silent streak when it sent an untitled letter to Xeris Pharmaceuticals concerning the company’s promotional practices for its high cholesterol treatment Recorlev (levoketoconazole).

The last time OPDP sent an untitled letter to a drugmaker was its letter to Althera concerning the company’s promotion of its cholesterol-lowering drug Roszet (rosuvastatin and ezetimibe) on 2 June 2022.

While drug promotion enforcement activity has declined in recent years, the lengthy gap since OPDP’s last enforcement letter did not go unnoticed. A recent article in Policy & Medicine asked “OPDP: No More Untitled Letters?” and AgencyIQ marked the anniversary since the previous OPDP untitled letter in their 2 June 2023 newsletter.

Recorlev is specifically indicated to treat high cholesterol, or endogenous hypercortisolemia in adults with Cushing’s syndrome that are not eligible for surgery or for patients whose surgery was not curative.

FDA said the company’s promotional communications on its website made “false and misleading claims and representations about the safety and efficacy of Recorlev,” which the agency said is particularly concerning given the “number of serious and potentially life-threatening risks, including boxed warnings.”

Recorlev’s label carries two boxed warnings detailing the risks of hepatotoxicity and QT prolongation. The drug is also contraindicated in more than a dozen uses, including in patients with cirrhosis, acute liver disease or poorly controlled chronic liver disease, recurrent symptomatic cholelithiasis, and in patients taking drugs that cause QT prolongation associated with ventricular arrhythmias.

At issue are the companies claims about the efficacy and safety of the drug. FDA said that two claims on the company’s “What is Recorlev?” webpage made two claims that misrepresented the drug’s efficacy by overstating the number of patients who benefited from the drug.

In one claim, Xeris stated 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.” FDA said this is misleading because it represents the percentage of patients that had normal cortisol levels at the end of the study’s titration phase; “however, the titration phase was not the ‘end of the study.’”

FDA said the claim omitted “material information necessary to interpret any results from the SONICS study” by leaving out an advisory from the prescribing information that notes that “[b]ecause 51% of patients discontinued treatment prematurely due to adverse reaction, lack of efficacy, or other reasons, these results should be interpreted with caution.”

Additionally, FDA said that the company’s claim that 52% of patients “who were on a stable dose of Recorlev had normal cortisol levels” was misleading because it is “based on a small, select subset of patients enrolled in the study who had already demonstrated that they were able to tolerate and respond to the drug.”

The agency also found that the company’s “Taking Recorlev” webpage downplayed the drug’s risks by using language such as “side effects can occur with Recorlev, including some that are serious.” FDA said this “minimizes” the serious and potentially fatal adverse events associated with the drug and points out that the prescribing information states that 13% of patients taking the drug experienced drug-induced liver injury and that some adverse reactions noted on the label occurred in more than 20% of patients.

FDA asked the company to respond to the letter within 15 days to address its concerns and to provide a plan for discontinuing its communications that feature the problematic statements, or to cease distribution of the drug.

FDA

OPDP hands first untitled letter in twelve months to Xeris

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