The prominent consumer watchdog group Public Citizen is calling for federal drug regulators to issue a Victoza recall, indicating that the injectable diabetes drug carries too high a risk of acute pancreatitis for users.
On June 5, Public Citizen sent a letter to the FDA (PDF) demanding that Victoza be banned immediately from the U.S. market. The letter comes on the heels of the FDA’s denial of a previous petition calling for a recall of Victoza.
Public Citizen first petitioned the FDA to remove Victoza from the market in 2012, due to several safety concerns and what Public Citizen says are marginal benefits. The FDA rejected (PDF) that request on March 25, indicating that the agency has required the drug maker to include pancreatitis and other risks on the Victoza label.
The group is again calling for the diabetes drug’s recall, based on a new analysis of Victoza adverse events (PDF), which the consumer advocacy group has filed with the FDA.
Victoza (liraglutide) was approved by the FDA in January 2010 for the treatment of type 2 diabetes. The Novo Nordisk drug is a member of a class of diabetes drugs known as incretin mimetics, which also includes Byetta, Januvia, Janumet and others. Two FDA pharmacologists and one clinical safety reviewer advised against the approval of Victoza at the time it was proposed by the drug maker.
According to Public Citizen, within 17 months of its approval, there were more than 200 cases of pancreatitis among Victoza users, and the FDA was required to go back and add warnings for pancreatitis, thyroid cancer, and kidney failure.
“Public Citizen is extremely troubled by FDA’s decision to deny our petition and keep liraglutide on the market,” the letter states. “Given the range of known safer, alternative pharmacologic and non-drug treatments for diabetes, this decision to allow continued sales of liraglutide will unnecessarily continue to expose hundreds of thousands of patients to the drug’s serious risks.”
Public Citizen points to the new study as increasing evidence that Victoza has no place on pharmacy shelves. It comes as some doctors have suggested using Victoza to treat obesity, which would require a much larger dose than that given to diabetics.
Public Citizen’s study found 278 unique case reports of acute pancreatitis linked to Victoza use. They found that 30% of the cases appeared within one month of starting Victoza therapy, and 72% of the cases occurred within four months. The study found that 60% of the Victoza pancreatitis cases required hospitalization and three of the patients died, with at least two of them dying from complications of acute pancreatitis.
From the evidence available, Public Citizen researchers were able to determine that Victoza was the probably cause of at least 51 of the cases, and was highly probable in 12 of those. One case was strong enough for the group to conclude that Victoza was definitely the cause.
Researchers with Public Citizen determined that there is strong evidence of a causal link between Victoza and acute pancreatitis.
“Because of the low reporting rates to the FDA’s database, the 278 cases we found likely represent a small fraction of patients who have developed acute pancreatitis while using luraglutide,” Dr. Sammy Almashat, co-author of the study, said in Public Citizen’s press release. Many researchers estimate that only about 10% of cases are actually reported to the FDA’s Adverse Event Reporting System, which is voluntary.
Pancreatic Cancer Concerns
A number of other studies have also suggested a possible association between use of Victoza and pancreatic cancer. Though none have demonstrated a cause and effect relationship, which is traditionally hard to find, a growing number of pancreatic cancer lawsuits are being filed over Victoza, as well as other incretin mimetic diabetes drugs.
A study published in October 2013 looked at 1,169 adverse drug reaction reports, and identified at least 90 cases of users of incretin mimetics suffering from pancreatitis and elevated pancreatic enzymes. Acute or chronic pancreatitis can lead to the development of pancreatic cancer in some cases.
In February 2013, researchers from Johns Hopkins in Baltimore found that taking Januvia or Byetta may double the risk of hospitalization due to pancreatitis, which raised concerns about whether this may also suggest an increased risk of pancreatic cancer.
In March 2013, the risk of pancreatic cancer from Januvia, Byetta and other incretin mimetics gained additional attention after another study published in the medical journal Diabetes found that pancreas tissue from organ donors found that those who took an incretin mimetic were more likely to have increased pancreatic mass and precancerous cells, which are cells with the potential to evolve into tumors.
Following these reports, the FDA and European drug regulators launched an investigation to evaluate the potential pancreatic cancer risk with Byetta, Januvia and other incretin mimetic drugs. However, in August 2013, the regulatory agencies concluded that the existing data available at that time was unable to confirm an increased risk of pancreatic cancer.
Diabetes Drug Litigation
Amid mounting concerns about the link between the diabetes drugs and cancer, hundreds of Byetta lawsuits, Januvia lawsuits, Janumet lawsuits and Victoza lawsuits have been filed by individuals throughout the United States who claim that they were diagnosed with pancreatic cancer after using the drugs.
Byetta (exenatide) was the first member of the incretin mimetic class of diabetes drugs, which was introduced by Amylin Pharmaceuticals in 2005 as a twice daily injection. Novo Nordisk introduced Victoza in 2010, as a longer acting injectable diabetes drug and Amylin introduced Bydureon (exenatide extended-release) in January 2012 as a once-weekly version of Byetta.
Januvia (sitagliptin) was introduced by Merck as an oral incretin mimetic diabetes drug in 2006, and has become one of the most widely used members of the class. A combination pill containing Januvia and the older diabetes medication metformin was introduced in 2007 under the brand name Janumet.
Given the similar allegations raised in lawsuits over the diabetes drugs, the U.S. Judicial Panel on Multidistrict Litigation (JPML) established consolidated proceedings in the federal court system for these cases in August 2013. There are currently more than 350 complaints centralized before U.S. District Judge Anthony J. Battalglia in the Southern District of California to reduce duplicative discover, avoid conflicting pretrial rulings from different judges and to serve the convenience of the parties, witnesses and the courts.
It is expected that a small group of cases in the federal Multidistrict Litigation (MDL) will be prepared for early trial dates, known as “bellwether” cases because they will be used to gauge how juries may respond to certain evidence and testimony on the link between increatin mimetics and pancreatic cancer. The first cases are unlikely to reach a jury before late 2015 or early 2016.