On June 2, 2022, Althera received an Untitled Letter from OPDP regarding its promotion of Roszet (rosuvastin and ezetimibe) tablets, indicated as adjunctive to diet in patients with non-familial hyperlipidemia to reduce LDL cholesterol (LDL-C), as well as alone or as an adjunct to other LDL-C-lowering therapies in patients with homozygous familial hypercholesterolemia to reduce LDL-C. The letter concluded that the drug had been misbranded based on allegations that Althera had misrepresented statistical analyses in making outcomes claims, as well as that it had minimized risk information, in manners that were false or misleading.
The promotional piece in question was a physician-directed brochure with a series of claims regarding percent-reductions in LDL-C by dosage amount (“Roszet 10 mg/10 mg: 64%; Roszet 20 mg/10 mg: 66%; Roszet 40 mg/10 mg: 72%”) and from two of Roszet’s clinical trials (depicting reductions in LDL-C from its GRAVITY Study and its EXPLORER Study). Problematic to OPDP was the statistical analysis used to arrive at these claims. In the LDL-C-reduction section, these numbers appear not to be the findings of a particular study, but rather an Althera calculation combining results from two separate studies with disparate therapies studied (one a monotherapy study; one a combination study including an ongoing statin), patient populations, durations, and endpoints. FDA found no scientific basis for combining study results in this manner. In depicting reductions from its two clinical studies, OPDP highlighted that the brochure misstated the conclusions by failing to provide key study-design information, including that the GRAVITY study involved 6 weeks of monotherapy followed by six weeks of combination therapy (noting that the brochure prominently states “Patients Can Get Below 70 mg/dl with One Pill Daily”) and that achieving 70 mg/dl was only one of many secondary endpoints that did not control for multiplicity testing of secondary endpoints. These outcomes claims, therefore, created a false or misleading impression of efficacy of Roszet.
Additionally, OPDP found the brochure lacking in risk information in a way that minimized the risks in comparison to the benefits. The brochure failed to present Roszet’s contraindications, warnings, and precautions with prominence and readability reasonably comparable with the presentations of benefits, as demonstrated by the “typography, layout, contrast, headlines, paragraphing, white space, and other techniques apt to achieve emphasis.” By minimizing the risks associated with the drug, FDA concluded that the brochure was false or misleading.