According to the FDA’s Office of Prescription Drug Promotion (“OPDP”), Marc Beer, the CEO of biopharmaceutical firm Aegerion Pharmaceuticals, overstepped his bounds when he allegedly made misleading statements about Aegerion’s cholesterol-lowering drug, Juxtapid™ on two televised appearances on CNBC. As a result, Aegerion received a warning letter earlier this month from OPDP, admonishing Beer for his transgressions, accusing the Company of misbranding Juxtapid™ and asking for corrective action. Although it makes business sense for Aegerion to “play ball” with the FDA and do whatever it takes to convince the agency that there was no intent to promote Juxtapid™ off-label, Beer’s comments are a reminder of the free speech issue embedded in any discussion about a drug or device product that falls outside the friendly confines of the product’s labeling.
Last December, the FDA approved Juxtapid™ (lomitapide) oral capsules as an adjunct to a low-fat diet and other lipid-lowering treatments to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B) and non- high-density-lipoprotein cholesterol (non-HDL) in patients with homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder in which patients suffer from excessively high levels of LDL cholesterol at a very young age, putting them at risk for heart disease, stroke and death. Importantly, the “Indications and Usage” section of the FDA-approved product labeling for Juxtapid™ includes the following:
- Juxtapid™ is indicated as an adjunct to a low-fat diet and other lipid lowering treatments in patients with HoFH.
- The safety and effectiveness of Juxtapid™ have not been established in patients with high cholesterol who do not have HoFH.
- The effect of Juxtapid™ on cardiovascular morbidity and mortality has not been determined.
Although the most common adverse reactions associated with Juxtapid™ include diarrhea, nausea, vomiting, dyspepsia, and abdominal pain, there are also a number of serious risks and contraindications associated with the use of Juxtapid™, including liver toxicity. As a result, the drug is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (“REMS”) where certification of healthcare providers and pharmacies is required in order to prescribe and distribute the drug.
In its warning letter to Aegerion, the FDA singled out two dates when CEO Beer made statements on CNBC that (according to the agency) suggested that Juxtapid™ was safe and effective as a monotherapy treatment, as well as decreasing the occurrence of heart attacks and strokes in, and increasing the lifespan of, patients with HoFH. Specifically, the FDA warning letter quoted the following of Beer’s statements which aired on CNBC’s “Fast Money” on June 5:
- “In these [HoFH] patients, they have a devastating disease. They have a lethal level of cholesterol, bad cholesterol, which we call LDL, going through their blood stream. And they’re born with this disease and often not diagnosed until 8, 10 years of age when they have a heart attack. If you can imagine a child having a heart attack at 8, 10, 12 years of age. And then they have another event, usually about every 18 months, and die by the age of 30. And we’ve found out that we can lower it significantly with this drug. . . .”
- “It’s a devastating disease that causes early death. And the drug is corrective against that disease and that’s the most important thing. If you think about some oncology products that may lengthen life three months or six months, this product has the potential of taking a patient that would die at 30 and allow them to meet their grandkids.”
The agency also referenced the following statement Beer made during an October 31 airing of another CNBC appearance:
- “These patients are going to die of a cardiac event, either a stroke or a heart attack, if we don’t have them on therapy.”
According to the warning letter, “the approved labeling for Juxtapid™ does not provide instructions for, or otherwise indicate that Juxtapid™ will be safe and effective if used, either to reduce the occurrence of cardiovascular events in HoFH patients and to increase their lifespans, or as a stand-alone therapy for reducing lipids in these patients.” The FDA warning letter went on to state that Beer’s statements “provide evidence that Juxtapid is intended for new uses, for which it lacks approval and for which its labeling does not provide adequate directions for use, which renders Juxtapid misbranded within the meaning of the FD&C Act and makes its distribution violative of 21 U.S.C. 352(f)(1), 331(a); 21 CFR 201.5, 201.100, 201.115, 201.128.” The agency further demanded that the Company submit a written response by November 22nd, stating if the company will comply with the OPDP’s request to list and immediately discontinue the use of materials that misbrand Juxtapid™, or alternatively, cease to distribute the drug. According to OPDP, if Aegerion does not comply, it will risk FDA regulatory action including, but not limited to, seizure or injunction.
One year of Juxtapid™therapy is not cheap, costing around $250,000, and Aegerion has argued that the number of patients with HoFH is greater than originally determined. However, some experts have reservations, questioning whether Aegerion is trying to promote Juxtapid™ to patients who have dangerously high cholesterol, but do not have HoFH. According to a November 11 article on TheStreet, Beer said in a recent investor meeting that the Company was “on track to have the most successful launch in the orphan industry” and that peak sales of Juxtapid™ could exceed $1 billion. Juxtapid™, which competes with Kynamro, another HoFH drug marketed by Isis Pharmaceuticals and the Genzyme unit of Sanofi, is clearly an important franchise to Aegerion.
Consequently, in response to the FDA’s warning letter, Aegerion issued the following statement:
We take regulatory compliance very seriously and acknowledge that our messaging in any setting, including a media interview as in this particular instance, needs to be accurate and fair balanced. Our plan is to take quick action in response to the FDA’s letter and immediately and effectively address any unsuitable language. We appreciate that the FDA’s objective is to ensure that promotion is consistent with approved labeling, and in that respect we are aligned with the agency.
While I can certainly understand why Beer and Aegerion want to “make nice” with the FDA and avoid an enforcement action, it is unclear from anything I have read whether Beer’s statements were based on any scientific data. If that had been the case, Beer’s comments would not be that different from the kind of statements that InterMune CEO Scott Harkonen made in a 2002 press release about the Phase 3 clinical trial results for FDA-approved Actimmune — statements for which he was ultimately indicted and convicted for wire fraud. Harkonen, who wrote the press release himself, had suggested that, despite the failure of the trial to show that Actimmune was effective in delaying the progression of idiopathic pulmonary fibrosis (“IPF”), a rare and fatal lung disease, there was data supporting “a survival benefit of Actimmune in IPF”, that the drug “reduces mortality by 70% in patients with mild to moderate IPF”, and that approvals for the new indication could lead to an additional $500 million in Actimmune sales for InterMune. The Government went after Harkonen, convincing a jury, the federal district trial judge and the Ninth Circuit Court of Appeals that Harkonen intended to mislead and defraud investors about the data — even though InterMune proceeded to conduct a follow-up trial to test Actimmune’s effectiveness in treating patients with mild to moderate IPF.. Harkonen has since petitioned the U.S. Supreme Court to take up his case and has made a compelling argument that his wire fraud conviction rests on statements he made “interpreting” scientific data that was subject to debate at the time. If the Court grants the petition, Messrs. Harkonen and Beer — and everyone else who was left “hanging” by the Government when it failed to appeal the Second Circuit’s Caronia decision last December — may yet get their chance to learn exactly how far the First Amendment protects off-label speech.