FDA’s OPDP takes Althera to task over cholesterol drug promotion

The US Food and Drug Administration (FDA) has admonished Althera Pharmaceuticals for misrepresenting the efficacy and risk profile of its cholesterol-lowering drug Roszet (rosuvastatin and ezetimibe) in promotional materials. The agency said the company used a faulty analysis to show the drug’s effectiveness and underplayed its risks.
 
On 7 June, FDA’s Office of Prescription Drug Promotion (OPDP) published an untitled letter to Althera dated 2 June that raised concerns about how the company promotes Roszet. The agency noted that the drugmaker has made certain claims about how much its pill can lower low-density lipoprotein cholesterol (LDL-C) based on analysis of two separate studies. The problem, according to regulators is that the studies do not prove such effectiveness and the company is misrepresenting the data. The letter is the third untitled letter sent by OPDP to a drugmaker in 2022.
 
FDA notes the first study was a monotherapy study that evaluated rosuvastatin in patients with hyperlipidemia while the second study was a combination study that evaluated ezetimibe added to ongoing statin therapy in patients with primary hyperlipidemia, known coronary heart disease or multiple cardiovascular risk factors, in patients who were already receiving statin monotherapy, but who had not met their target LDL-C goal. The inferences made from those unrelated studies were retrospectively calculated by Althera according to regulators, but do not prove the claims the company makes in their promotional materials.
 
“The LDL-C reductions claimed in the promotional communication for each dose of Roszet were calculated by taking the percent change from baseline LDL-C reduction observed in the rosuvastatin monotherapy study and then applying an additional 25% LDL-C reduction which was observed in the separate ezetimibe added to ongoing statin therapy study,” regulators said. “FDA is not aware of a scientific basis for combining study results in this manner.”
 
FDA also notes that the studies had a number of significant differences, such as patient population, type and dose of statins and duration of treatment that would preclude someone from making any conclusions based on the combined data.
 
“Such differences between studies limit the interpretability of any cross-study comparisons and any analysis combining the results of these studies,” the agency said. “Thus, such an analysis does not support these claims that attribute specific levels of LDL-C reductions to each dose of Roszet.”
 
“The clinical studies described in the Roszet PI and cited in the promotional communication support FDA’s finding of safety and efficacy of the drug with respect to its labeled indication, involving the reduction of LDL-C in certain patients, but not in achieving the specific levels of LDL-C reductions claimed,” they added. “Thus, the promotional communication creates a misleading impression regarding the effect of Roszet.”
 
In addition to the efficacy claims, FDA said the company downplayed potential risks and contraindications. The agency notes that Roszet is contraindicated in patients with acute liver failure or decompensated cirrhosis and in patients with hypersensitivity to rosuvastatin, ezetimibe, or any excipients in Roszet.
 
Regulators said that Althera is supposed to warn patients about potential risks for myopathy and rhabdomyolysis, immune-mediated necrotizing myopathy, hepatic dysfunction, proteinuria and hematuria, as well as increases in HbA1c and fasting serum glucose levels.
 
They also note that the most common adverse reactions reported with rosuvastatin were headache, nausea, myalgia, arthralgia, dizziness, asthenia, constipation and abdominal pain; and with ezetimibe were upper respiratory tract infection, diarrhea, arthralgia, sinusitis, pain in extremity, fatigue, and influenza. When ezetimibe is co-administered with a statin, they note the most common side effects include nasopharyngitis, myalgia, upper respiratory tract infection, arthralgia, diarrhea, back pain, influenza, pain in extremity and fatigue.
 
While the company played up potential benefits of Roszet and its excipients in their promotional material, FDA said Althera failed to highlight risks and contraindications to the same degree.
 
“The promotional communication is misleading because it fails to present information relating to the contraindications and warnings and precautions for Roszet with a prominence and readability reasonably comparable with the presentation of information relating to the benefits of Roszet,” said the agency. “Specifically, benefit claims for Roszet are presented in conjunction with colorful graphics and large bolded headlines, with significant white space. However, risk information regarding some of the contraindications is relegated to the bottom of the first page and the remaining contraindications and warnings and precautions are presented on a subsequent page. This risk information is also presented in small font and in paragraph format.”
 
FDA has asked Althera to respond to its untitled letter within 15 days either with details on how it will correct the issues the agency has raised about its promotional materials, or with an explanation on how it is not in violation of regulations.
 
Regulatory Focus has reached out to Althera for comment and will update this story accordingly.