Will Sanofi's Lantus Survive Cancer Scare? Studies Suggest a Worrisome Link

But the data also suggest a higher cancer risk could be due to "patient characteristics," and not Lantus itself.

The fate of Sanofi-Aventis' once-daily insulin analog Lantus and perhaps other similar products hang in the balance after studies published in the respected European journal Diabetologia raised the specter of a cancer risk in humans.

Four new retrospective studies of patient registries in European countries and an accompanying editorial are set to be published in Diabetologia, the official publication of the European Association for the Study of Diabetes in July. Advance copies of the papers and a statement about the results were available on the Diabetologia website on June 26.

Three of the studies show a higher incidence of cancer in people taking Lantus (insulin glargine) compared to human insulin, although the results were not statistically significant in one study. However, the results could be more of a reflection on patient characteristics, such as higher blood pressure, advanced age and weight, rather than on Lantus itself, according to the EASD statement.

Sanofi shares took a beating as word of negative research in a major medical journal leaked out. Approved in 2000, Lantus has become Sanofi's second-biggest product and has been on a "non-stop trajectory," Bernstein Research analyst Tim Anderson wrote in an investor note. He had projected product sales of €3 billion ($4.2 billion) in 2009 and €5 billion ($7 billion) in 2015.

"On balance, this is not horrific and importantly, it is not alarmist. That said, Lantus is still likely to see contraction to an uncertain degree. As the core driver of Sanofi-Aventis's earnings going forward, this will probably continue to weigh on the stock."

Sanofi said "no definitive conclusions can be drawn for a causal relationship between Lantus use and occurrence of malignancies."

"Given the extensive evidence with over 70,000 patients and the results of post-marketing surveillance from 24 million patient years experience, Sanofi stands behind the safety of Lantus," the company said in a statement.

Human insulin safety is "beyond doubt," notes EASD

The safety of human insulin is "beyond doubt," whereas further research is needed to establish the safety of Lantus, an "artificial form of insulin," according to the EASD statement. The EASD stopped short of advising patients to discontinue using Lantus, but also noted that since Lantus does not offer better overall glucose control than human insulin in type 2 diabetes, patients can consider alternatives.

"People with diabetes do have the option of using long-acting human insulin or a mixture of long- and short-acting human insulin twice a day instead of the once-daily analogue. You may wish to consider this option if you already have a cancer, or, for women, if there is a family history of breast cancer," the statement said.

EASD proposes a new larger analysis of the "best available databases worldwide" to get to the bottom of the safety questions.

One of the studies published in Diabetologia looked at insurance claims data for 127,000 patients in Germany. That study identified a statistically significant higher incidence of cancer for patients taking Lantus insulin compared to human insulin.

In light of these results, similar studies were then conducted in Sweden, Scotland and the United Kingdom. The Swedish and Scottish studies showed a higher risk for breast cancer, though the result was not significant in the Scottish study, and the U.K. study found no such link with cancer.

Among other limitations of the new studies, the patients taking Lantus alone were generally older, had higher blood pressure and weighed more, than diabetics on alternative medications, according to the EASD statement.

"Thus any difference in cancer risk could be attributed to the pre-treatment characteristics of the groups, rather than the treatment itself," trial investigators said in the statement.

Will cancer scare tarnish Lantus?

Some say the mere mention of the "C" word is enough to kill a drug off, even when study results are not conclusive.

Other drugs have found rebounding from safety scares difficult. Prescriptions of GlaxoSmithKline's Avandia (rosiglitazone) fell by 80 percent after meta-analyses released in 2007 showed increased risk for cardiovascular events. At the recent American Diabetes 2009 meeting, the company released results from the long-term study RECORD that many doctors believed set the safety record straight on safety, but commercially speaking, the story is probably over.

Negative news on Lantus could benefit non-insulin products like Merck's DPP-4 inhhibitor Januvia (sitagliptin) and Eli Lilly/Amylin's GLP-1 agonist Byetta (exenatide), Anderson wrote prior to the publication of results.

The effect on other insulin analogs like Novo Nordisk's Levemir (a long-acting insulin analog like Lantus) as well as short-acting insulin drugs, is more difficult to predict.

- Emily Hayes ( ¹ [email protected] )