Januvia, Byetta, Claims Headed for Appeals Court

The fate of diabetic patients who suffered pancreatic or thyroid cancer after ingesting incretin-based therapy drugs is now in the hands of the Ninth Circuit Court of Appeals after the claims were dismissed by the California federal court judge who oversaw the national coordinated litigation. In September of 2016, the plaintiffs whose individual lawsuits were dismissed by the MDL judge argued that the trial court had misinterpreted previous rulings of the United States Supreme Court on brand name drug preemption, and that individual lawsuits against the drug manufacturers for failure to warn of the risks of pancreatic cancer, thyroid cancer, and pancreatitis should have been permitted to proceed in MDL No. 2452. In these lawsuits, the plaintiffs argued that the drug manufacturers knew or should have known (had they conducted adequate research prior to drug approval) that ingestion of Byetta, Januvia, Janumet or Victoza increased the risks of developing pancreatitis, which, in turn, increased the risk of developing pancreatic cancer.

History of Januvia, Byetta

Byetta (also known as exenatide) received FDA approval in April of 2005. Sales of Byetta in 2014 were approximately $3.5.8 billion worldwide. Byetta is jointly marketed by Eli Lilly and Amylin Pharmaceuticals.

Januvia (also known as sitagliptin) was approved by the FDA in October of 2006 to be used as stand-alone therapy or to be prescribed in conjunction with metformin, one of the most commonly prescribed diabetes drugs, or thiazolidinediones (a class of drugs that includes the beleaguered Avandia and Actos, which have both been under a cloud for many years due to safety concerns). Janumet, a combination of Januvia and metformin, was the next drug in this class to be approved by the FDA in 2007. Januvia is one of Merck’s best-selling medications, with sales of more than $5.8 billion in 2012, and Janumet also enjoys sales in excess of $2 billion per year.

Victoza (also known as liraglutide) was the last drug of this group to be approved by the FDA I January of 2010. Victoza is manufactured by Novo Nordisk, which is based in Denmark. The FDA’s approval of Victoza included special requirements (including post-marketing studies to address potential safety issues and enhanced information to be provided to patients). During the clinical trials prior to approval of Victoza, it was noted that patients taking Victoza had a higher risk of developing pancreatitis (an inflammation of the pancreas) over patients taking other diabetes medications. In 2011, Victoza had sales in excess of $1 billion, which is considered “blockbuster” status for a drug.

As early as February of 2010, a concern arose in the scientific community that ingestion of Victoza, Byetta, Januvia, or Janumet might be associated with an increased risk of pancreatic cancer. This was particularly alarming to diabetics, as many had previously ingested Rezulin (linked to liver failure), Avandia (linked to heart attacks), and Actos (linked to bladder cancer). Later studies had conflicting results as to whether patients taking incretin-based therapy drugs had a higher risk of not only pancreatic cancer but also thyroid cancer and pancreatitis. Some animal studies also supported the plaintiffs’ claims that incretin-based drugs increase the risk of pancreatitis.

An examination of the FDA’s Adverse Event Reporting System was undertaken in hopes of further evaluating the potential cancer risks as well as whether there were excessive cases of pancreatitis (which is a known risk factor for the development of pancreatic cancer). This adverse event report analysis noted a 290% increased risk of pancreatic cancer in patients taking Byetta and a 270% increased risk in patients taking Januvia over other diabetes drug therapies. A similar spike in adverse event reports was noted in the German agency that oversees drug safety in that country. The drug companies have reportedly attributed the increased reporting of pancreatic cancer in the drug regulatory safety databases to an increased risk of pancreatitis in diabetic patients in general.

In 2012, Public Citizen, the public safety non-profit established by Ralph Nader, petitioned the FDA to remove Victoza from the market. Public Citizen’s research indicated that the FDA had received reports of 28 cases of pancreatic cancer in patients taking Victoza in an 18-month time period. In February of 2013, an epidemiological study was published by researchers with Johns Hopkins who had studied insurance records in hopes of quantifying the risks of acute pancreatitis in patients taking these drugs and noted a statistically significant increased risk in this particular patient group.

Recent Rulings on Januvia, Byetta

On August 26, 2013, the Judicial Panel on Multidistrict Litigation created MDL No. 2452 and consolidated a number of individual products liability lawsuits involving personal injury and wrongful death claims related to various diabetes drugs. The multi-district litigation was based in the Southern District of California before United States District Court Judge Anthony J. Battaglia. The consolidated proceedings included claims against Merck, Novo Nordisk, Amylin Pharmaceuticals, and Eli Lilly relating to incretin-based therapy drugs (including Januvia, Janumet, Byetta, and Victoza). Byetta and Victoza are glucagon-like peptide-1 (GLP-1) receptor agonists, while Janumet and Januvia are dipeptidyl peptidase-4 (DPP-4) inhibitors. These brand name drugs are widely prescribed to patients with Type 2 diabetes mellitus to lower blood sugar levels.

Within the summary judgment order that led to the essential demise of the MDL for these drugs, Judge Battaglia essentially ruled that the FDA would not have permitted the manufacturers to include a warning regarding the risks of pancreatic cancer on the warning label for the drugs if the manufacturers had sought such approval. In a complex series of previous court rulings, the United States Supreme Court and various federal courts have ruled that a brand name drug manufacturer cannot be held liable for failure to provide a proper warning if it can show that the FDA would not have approved the enhanced warnings that the plaintiffs argue should have been included with the product.

The judge found in his dismissal order that the FDA had specifically commented in public statements about what the drug safety agency deemed to be conflicting scientific evidence regarding the potential link between these diabetes drugs and pancreatic cancer. The judge determined, based upon these statements, that the FDA would have rejected a request by a drug manufacturer to enhance the warning label for the product.

The concept behind this type of federal preemption is that individual plaintiffs should not be able to attempt to hold a drug company to a higher standard than that of the FDA. The problem, however, is that the FDA is not necessarily at the forefront when it comes to drug-related safety issues. This is for a number of reasons, including the fact that FDA conducts no independent safety testing of drugs; the agency is funded, in part, by user fees paid by the same drug companies that the agency is supposed to be overseeing; the leadership of the FDA are political appointees; and the FDA has to weigh the commercial interests of its “clients” (the drug companies) versus patients.

Drug companies have an obligation to report safety issues to the FDA and to look for signals of potential safety issues. The problem, however, is that studies can be interpreted in a number of ways, especially when there are several to choose from, such that the manufacturer can find reasons not to report safety issues and the FDA can choose not to alert patients and prescribing physicians of potential safety threats if it deems the scientific studies unreliable. The bottom line is that patients end up with inadequate safety information which leads to avoidable patient injuries and deaths, and the injured patients are then left without a legal remedy due to brand name drug preemption which provides immunity for drug companies. Hopefully, the plaintiffs harmed by the incretin mimetic drugs will prevail in their appeals to the Ninth Circuit Court and, likely, the United States Supreme Court.