AstraZeneca Strives to Block Generic Crestor as Observers Call Foul

US Senator Bernie Sanders (D-VT) and several members of the House of Representatives are asking the Food and Drug Administration (FDA) to approve all eligible generic versions of Crestor, arguing that the current legal wrangling by AstraZeneca, the company that manufactures the cholesterol-lowering medication, is a blatant attempt to block generic competition and maximize profit.

Market exclusivity for Crestor should have expired on July 8, 2016, but AstraZeneca filed a citizen petition with the FDA in late May to block the approval of generic rosuvastatin and sued the agency on June 27, 2016, in the US District Court for the District of Maryland. Lawyers for the company are arguing that the agency should not approve any generic versions of the popular lipid-lowering medication, the reason being that AstraZeneca was awarded a 7-year exclusivity extension for Crestor under the Orphan Drug Act for the treatment of pediatric patients with homozygous familial hypercholesterolemia (FH).

“AstraZeneca has already enjoyed 12 years of market exclusivity for Crestor with revenues over $16 billion from Crestor in the last 3 years alone,” state Sanders and colleagues in their letter to the FDA. “Those exclusivity periods have now come to an end. Any additional regulatory exclusivity AstraZeneca has obtained under the Orphan Drug Act does not cover all uses, especially those no longer protected by patents or exclusivities.”

For Joseph Ross, MD (Yale School of Medicine, New Haven, CT), a researcher who studies public health policy, the legal move by AstraZeneca is an orchestrated effort to extract more money from their popular statin.

“The company’s decision to file suit against the FDA to prevent generic versions of rosuvastatin to be sold is an obvious attempt to prolong the profitability and brand-name sales of Crestor,” he told TCTMD in an email. “Others, like Public Citizen, have warned how this Orphan Designation approval would be abused to extend market exclusivity. AstraZeneca is providing a real-life example, having obtained approval for a rare indication just as generic competition nears, knowing that nearly all prescriptions for the drug will continue to be written for adults with high cholesterol.”

Others agree, noting that AstraZeneca only began testing rosuvastatin in children and adolescents with homozygous FH in the HYDRA clinical trial in 2014. Sidney Wolfe, MD, senior advisor to Public Citizen, told the New York Times that if AstraZeneca was truly interested in this rare disease, they’d have studied it “a long time ago, not right before midnight when it is about to turn into a pumpkin.” Similarly, Walid Gellad, MD (University of Pittsburgh, PA), told Stat News the move is not about finding a way to treat children with rare homozygous FH, “it’s a way to extend [the] life of a brand-name drug.”  

Homozygous FH Very Rare in US

To comply with patent protection, the FDA would likely “carve out” the pediatric homozygous FH label from generic rosuvastatin, which would omit the indication for which AstraZeneca enjoys marketing exclusivity. The agency took a similar carve-out approach in 2015 when they approved generic versions of an antipsychotic medication made by Otsuka Pharmaceuticals, a company that also attempted to thwart generic competition through legal and regulatory means.

In their legal interpretation, AstraZeneca contends that any generic rosuvastatin must include all labeling information—including the pediatric labeling—as brand-name Crestor. They argue the FDA can’t permit the multiple companies currently waiting to launch their generic versions of Crestor because these companies are not allowed to include the pediatric labeling information for homozygous FH. In the absence of the company’s protected pediatric homozygous FH label, AstraZeneca believes generic versions of Crestor pose a safety risk as physicians would not have proper guidance on how to dose the drug when treating such patients.

In court documents filed to have the Crestor case dismissed, the US Department of Justice argues that the move by AstraZeneca “is a transparent and manifestly premature attempt” by one of the world’s largest drug companies to block generic competition and that it is not about the needs of a small number of pediatric patients with homozygous FH. The federal motion states the “lawsuit is the latest in a long line of cases in which the manufacturer of a brand-name blockbuster drug product has attempted to stave off generic competition by whatever means it can dream up.”

To TCTMD, Sandy Walsh, a spokesperson for the FDA, said they would not comment on pending litigation or drug applications. AstraZeneca, through a spokesperson, also declined to comment on the ongoing legal process.

Homozygous FH is a rare disease affecting approximately one in a million patients, although some experts believe the prevalence might be higher, possibly as high as one in 160,000 to 300,000 individuals. At the low end, just 300 to 400 patients in the US have homozygous FH. The genetic disorder is marked by significantly elevated LDL cholesterol levels (500 to 1000 mg/dL), extensive xanthomas, and premature and progressive atherosclerotic cardiovascular disease, according to experts.

For Sanders, the legal maneuvering by AstraZeneca, based on an extremely small pediatric population with homozygous FH, is unfair to the 20 million patients who could benefit from a lower-cost generic equivalent. If the legal challenge by AstraZeneca were successful, it would be a “disastrous, anticompetitive, anticonsumer result,” according to the congressman.

Crestor has been approved for more than 12 years and has been one of the most widely prescribed branded drugs in the United States. The drug has consistently had annual sales in the $5 to $6 billion range for the last several years. According to Bloomberg, AstraZeneca makes $7 million per day from Crestor but the availability of several generic drugs would drastically cut into those sales. At present, there is one generic version of Crestor on the market. Made by Allergan, the generic rosuvastatin entered the market in May under a patent litigation settlement with AstraZeneca, according to the New York Times. 

Related Stories:

• Requiem for a Heavyweight: Big Brand Statin Era Comes to a Close as Crestor Heads Off-Patent
• JUPITER: Rosuvastatin Cuts Heart Risk, Even in LDL-Normal Patients
• PCSK9 Inhibitors: Good Early responses with Pricey Drugs, but Doctors Still Waiting on Real Data