Byetta Injury Information ( Byetta Has Not Been Recalled )

CLINICAL

New Anti-Diabetes Drug

The first of a new class of medications (incretin mimetics), Byetta (exenatide) was approved by the US FDA on April 28, 2005 for the treatment of type 2 diabetes.  Although patients must inject Byetta twice daily, it is not insulin.  Exenatide is a synthetic version of a hormone found in the saliva of the Gila monster, a lizard native to the southwest, giving rise to such nicknames as Lizzy and Gilly.  Byetta is approved "as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus who are taking metformin, a biguanide, or a combination of metformin and a sulfonylurea but have not achieved adequate glycemic control".  It is also approved for use with thiazolidinediones such as pioglitazone or rosiglitazone.

Dr. John Eng, an endocrinologist at the Bronx Veterans Affairs Medical Center in New York City discovered exenatide.  Exenatide works by mimicking the effects of a hormone called GLP-1.  It is believed to facilitate glucose control by increasing pancreatic secretion of insulin in response to eating; suppressing pancreatic release of glucagons in response to eating, preventing the liver from producing unnecessary sugar; slowing down gastric emptying; reducing appetite; and reducing liver fat content.  Byetta poses less risk of hypoglycemia than some other anti-diabetic agents and has been associated with weight loss, although the drug is not indicated for weight reduction.

Side Effects

Although many diabetic patients appear to tolerate Byetta well, the drug's most common side effect is nausea, causing some patients to discontinue its use. The drug also causes a rash, fever and chills in some patients, although those effects often fade with continued use.

In an open-label randomized controlled trial of 551 patients, exenatide treatment for 26 weeks was associated with 2.3 kg weight loss; however, gastrointestinal symptoms were more common in the exenatide group, including nausea (57.1%), vomiting (17.4%) and diarrhea (8.5%).  Based on tests in rats, some scientists have speculated that Byetta may increase the risk of thyroid cancer, although no evidence of that link has appeared in human clinical trials. 

Acute Pancreatitis

But, it was 30 reports of acute pancreatitis in patients taking Byetta that led FDA to suspect an association between Byetta and acute pancreatitis and issue an alert on October 16, 2007.  The pancreas, a large gland behind the stomach, secretes enzymes that aid in digestion. Severe cases of pancreatitis may cause bleeding, tissue damage and infection, and lead to the release of toxins and enzymes into the bloodstream that can injure the heart, lungs, kidneys or other organs. The illness affects about 80,000 people a year and can be life-threatening, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

FDA Alert

FDA reported:  “Twenty-seven of the 30 patients had at least one other risk factor for acute pancreatitis such as gallstones, severe hypertriglyceridemia, and alcohol use.  In six patients the symptoms of pancreatitis began or worsened soon after the dose of Byetta was increased from 5 micrograms twice daily to 10 micrograms twice daily.  Twenty-one patients were hospitalized.  There were no reports of hemorrhagic or necrotizing pancreatitis.  However, five patients developed serious complications including dehydration and renal failure; suspected ileus; phlegmon; and ascites.  Twenty-two of the 30 reports indicated that the patients improved after discontinuing Byetta.

“Details in three reports indicated that the symptoms of acute pancreatitis returned when Byetta was restarted.  Nausea and vomiting returned in two patients when Byetta was restarted.  In a third patient, abdominal pain returned when Byetta was restarted and abated after Byetta was permanently discontinued.”

Symptoms of acute pancreatitis include persistent severe abdominal pain that can radiate to the back and may be accompanied by nausea and vomiting.  Acute pancreatitis is typically confirmed by the presence of elevated levels of serum amylase and/or lipase and characteristic findings by radiological imaging.   FDA instructed Byetta patients who experience unexplained persistent severe abdominal pain which may or may not be accompanied by vomiting to seek prompt medical care.  FDA added that Byetta should be discontinued if pancreatitis is suspected and not restarted unless an alternative etiology is identified.

FDA requested Byetta manufacturer Amylin Pharmaceuticals, Inc to include information about acute pancreatitis in the Precautions Section of the package insert and the company agreed.  Kindra Strupp, a spokeswoman for Lilly explained:  "Pancreatitis has been part of our label in post-marketing studies, so what you're seeing today is a clarification and update to the section.”

LEGAL

Amylin Pharmaceuticals and Eli Lilly jointly make and market Byetta,  Amylin is located in San Diego, California, and Eli Lilly is located in Indianapolis, Indiana.  The companies emphasized in a statement that reports of pancreatitis have been extremely rare, at 0.20 instances per 1,000 patients.

Byetta costs about $170 a month, or $2,100 a year, slightly more than most other diabetes drugs.  Lilly recorded $219 million in revenue from Byetta last year, while Amylin posted $430.2 million from the drug (accounting for more than 90% of the company’s revenue).  More than 700,000 patients worldwide have used Byetta since it was launched in June 2005.  In keeping with voluntary advertising guidelines, Lilly delayed direct-to-consumer advertising until September 2007.  Lilly declined to say how much it is spending on the campaign, but acknowledged it would be on the scale of recent direct-to-consumer marketing campaigns for Cymbalta and Cialis.

On the heels of the FDA Alert regarding pancreatitis, Amylin stock experienced its largest fall in almost two years, while Lilly's stock also dipped.  Amylin lost $2.45, or 5.1 percent, closing at $45.41, after earlier falling as much as 8.3 percent, its biggest drop since Oct. 27, 2005. Lilly shares fell 79 cents, or 1.4 percent, to close at $57.15.