Merck Joins Novo to Reassure FDA of Diabetes Drug Safety

Merck & Co., Novo Nordisk A/S and other makers of popular treatments for diabetes may be asked to collect more data on a potential cancer link even as they try to reassure U.S. regulators this week of the drugs’ safety.

The Food and Drug Administration said it’s considering setting up a study, either through the agency or the companies, that looks deeper into whether medicines for Type 2 diabetes, including Merck’s Januvia and Bristol Myers-Squibb Co.’s Byetta, cause pancreatic cell growth that could turn cancerous. One option is a large clinical trial designed to show patterns of adverse events, said Morgan Liscinsky, an FDA spokeswoman.

A debate swirled in the medical community in March with talk of unpublished findings that the FDA said may show pre-cancerous cellular changes in diabetics taking drugs called incretin mimetics. The FDA is reviewing the data and scientists from the agency and the companies are gathering today at the National Institutes of Health to sort it out.

“We need some calm heads and to look at the data and try and make some reasonable judgments out of this,” Robert Ratner, chief scientific and medical officer of the American Diabetes Association, said in an interview. “We are all anxious to be sure the therapies we have available are safe, but we also want to make sure we have therapies available.”

Encouraging Signs

According to documents distributed at today’s meeting, at least some FDA scientists said the report that arose in March didn’t really show a direct link to significant cancer risk. The scientists said additional data mining of the agency’s adverse event database “is unlikely to shed more light” and what is needed is “adequately powered, long-term epidemiological data.”

“The FDA basically appears to just be saying ‘look, there just isn’t enough information here to make an informed decision and the only evidence that will help us’” are properly designed trials, Mark Schoenebaum, an analyst with International Strategy & Investment Group, said in a note to clients. While it’s “too early to draw any kind of conclusion here, the early signs are encouraging.”

Incretin mimetics help regulate blood sugar by stimulating insulin production by the pancreas and their prescribing labels carry warnings about the risk of inflammation of the organ. Merck’s Januvia had $4.1 billion in revenue last year, while Novo’s Victoza generated $1.6 billion and New York-based Bristol-Myers’s Byetta $149 million, according to data compiled by Bloomberg.

2007 Reports

Doctors have been concerned that this category of diabetes treatments may damage the pancreas since the FDA said in 2007 it received a high number of reports of pancreatitis in those taking Byetta. The agency issued a similar alert for Januvia in 2009. An analysis of insurance records published in February in the journal JAMA Internal Medicine showed such drugs may double a user’s risk of pancreatitis.

Some data have been “overzealously interpreted,” said Alan Moses, global chief medical officer at Bagsvaerd, Denmark-based Novo Nordisk, which makes the drug Victoza.

“That’s a real challenge for patients out there who are taking this medicine and we have no conclusive evidence that there’s a problem and they’re being scared to death,” he said.

Moses will present interim data at the two-day NIH meeting from a post-approval study on incidence of thyroid cancer for Victoza users as well as pancreatitis and cancerous tumors.

Safety Assurances

“I am very reassured in the data that we have,” he said in an interview. “I am hoping the listeners in the room will be likewise reassured.”

Merck, the second-largest U.S. drugmaker, said it will present an updated safety analysis for Januvia, its top-selling product, using data from 25 trials. Peter Stein, vice president of clinical research for Whitehouse Station, New Jersey-based Merck, declined to say whether the FDA has talked to the company about an epidemiological study. He said the drugmaker is providing the agency with requested information.

Merck said in a statement today it’s willing to participate in an independent review of data called for by the American Diabetes Association.

FDA researchers plan to tell those gathered at the NIH meeting that animal studies conducted early in the regulatory review process for those drugs showed that data on pancreatic cellular changes are “weak to absent,” Liscinsky said in an e-mail.

Novo Database

“There has been no causal relationship established between exposure to incretin mimetics and pancreatitis, pancreatic cancer and thyroid cancer,” she said. “There have been several hypothesis generating studies, as well as many negative studies exploring these signals” in humans.

Novo is in the middle of a five-year epidemiological study using a large health-care claims database to look for incidence of thyroid cancer as well as pancreatitis and cancerous tumors.

Merck, Novo and Bristol-Myers also are conducting post-market studies on the heart safety of the diabetes drugs. Bristol-Myers said it and AstraZeneca Plc have two such trials that will provide additional data on the pancreatic risks as well. Data from the first of those trials is expected later in 2013, Bristol-Myers said in an e-mail.

Agnostic Group

While there is much dispute over the drugs’ safety, what is recognized is that diabetes and pancreatitis are associated with pancreatic cancer, said David Whitcomb, co-chairman of the NIH meeting and chief of the division of gastroenterology, hepatology and nutrition at the University of Pittsburgh.

A study published in March in Diabetes, the journal of the American Diabetes Association, on diabetics’ pancreases showed a 40 percent increase in cell changes that could lead to cancer for those taking incretin mimetics.

The meeting this week will attempt to better understand how the cancer develops and whether different treatments or biomarkers might be involved, he said. Whitcomb said he hopes the discussion will inform future studies.

“We’re an agnostic group that just wants to focus on the details of the organ,” Whitcomb said in an interview. “It is not to assess risk or benefit, that’s the job of the FDA.”