Companies counter insulin safety concerns

June 29, 2009 – 11:22 am by Gina Monari

Since Med Ad News‘ diabetes therapeutic feature was published last month, questions regarding the safety of insulin analogues such as the insulin glargine Lantus have surfaced. Now diabetes drug marketers Sanofi-Aventis SA and Novo Nordisk AS are engaged in rapid-fire PR initiatives to back the clinical evidence of their products.

On June 26, Diabetologia, the journal of the European Association for the Study of Diabetes, published online data from four studies relating to a possible link between a long-acting insulin analog, insulin glargine, and cancer. As a basis for such a possible link, an accompanying editorial explains that “certain insulin analogs have a structure making them more likely to bind to the IGF-1 receptor, which is known to be involved in promoting tumor growth.”

Sanofi-Aventis maintains that clinical trial evidence does not indicate an association between insulin glargine and cancer.

Analysts downgraded Sanofi-Aventis’ stock shares since Friday. Shares in Novo Nordisk, however, rose more than 5% Monday after the drug maker said it has not seen any cancer risks for the three insulin analogues it markets, Dow Jones & Co. reported.

Sanofi-Aventis says no definitive conclusions can be drawn regarding a possible causal relationship between use of the insulin glargine Lantus and the occurrence of malignancies, which were reported following a retrospective follow-up of four patient registries. Sanofi-Aventis says it continues to vigorously monitor the safety of Lantus in close collaboration with regulatory agencies and scientific experts.

A Sanofi-Aventis spokesperson pointed out to Med Ad News that patient safety remains the company’s first priority. In addition to the company’s official statement, Sanofi-Aventis states that:

• The analysis of registries/databases-derived data on the association of Lantus and cancer are inconclusive and inconsistent, as recognized by the authors themselves

• The recently published five-year long-term safety RCT does not support an increased risk of malignancy with insulin glargine compared to insulin

• Insulin is a fundamental treatment for patients with diabetes. It saves lives and protects from long-term complications, such as blindness, renal failure, limb amputations, and other vascular complications

• The carcinogenic potential of Lantus was carefully evaluated by the relevant regulatory agencies, and review of the available data revealed no convincing evidence to suggest an association between Lantus use and the development of cancer

Sanofi-Aventis spokespeople say the company is working with health authorities worldwide to ensure that healthcare providers have access to all the information they need to safely prescribe the company’s products, including Lantus, to their patients. In addition, people who have diabetes and are taking Lantus are being advised that they should not alter their course of treatment without first consulting with their treating physician.

At Sanofi-Aventis’ Website, there is a video message from Senior VP, Chief Medical Officer Dr. Jean-Pierre Lehner. The statement reinforces Sanofi-Aventis’ continued confidence in Lantus.

In addition to the video message, an investor relations conference call was held to highlight the company’s position. Company executives cited support from several organizations within the medical community, such as the American Diabetes Association.

Novo Nordisk supports that its own clinical evidence does not indicate an association between the company’s insulin analogues and cancer.

According to Sean Clements, associate director, media relations, Novo Nordisk, the company is communicating broadly with its patients and customers to instill confidence in the company’s products and their treatment.

“From internal training and outreach to key opinion leaders to communications through our patient education and physician portals, we are using all means at our disposal to convey confidence to patients and physicians that Novo Nordisk analog insulins provide a safe, effective, well-proven, and patient-friendly means of controlling blood glucose,” Mr. Clements told Med Ad News.

Novo Nordisk says its treatments — Levemir, NovoRapid/NovoLog, and NovoMix/NovoLog Mix 70/30 — have been studied in several trials, which did not identify any cancer signs. The company has issued the following points about Novo Nordisk’s insulin analogues to avoid unnecessary speculation about whether the products may be associated with an increased risk of cancer:

• Novo Nordisk’s insulin analogs have been tested for IGF-1 receptor binding in the early research phase and only insulins with a binding ratio between the insulin and IGF-1 receptors similar to, or better than, that of human insulin have been accepted for further development

• Studies on receptor binding and cell growth together show that insulin aspart, the insulin analog present in NovoRapid/NovoLog, and NovoMix/NovoLog Mix 70/30, has an in vitro safety profile that is identical to that of human insulin

• Studies on receptor binding have shown that Levemir in comparison to human insulin has a relative affinity to the IGF-1 receptor that is equal to or slightly lower than to the insulin receptor

• Levemir distinguishes itself from insulin glargine, which has been shown to have increased affinity for the IGF-1 receptor compared with human insulin

• All Novo Nordisk insulin analogs on the market have been studied in many randomized, controlled trials, in observational studies and are furthermore monitored for any safety signals through rigorous post-marketing safety surveillance. Novo Nordisk has not identified any cancer signals for any of the three insulin analogs

• Novo Nordisk has over the last 20 years discovered and developed insulin analogs to improve the treatment success rate for people with diabetes. Extensive clinical testing has provided evidence that Levemir, NovoRapid/NovoLog, and NovoMix/NovoLog Mix 70/30 possess clinical advantages for many patients with diabetes compared to human insulin

In a statement, the American Diabetes Association says the findings published in Diabetelogia “are conflicting and confusing.” The association cautions patients to talk with their doctor and not to stop taking their insulin.

“Four different population-based studies were reported and published in Diabetelogia and the data within these studies and between these studies are conflicting and confusing,” the ADA says. “Until more information is available, the American Diabetes Association advises patients using insulin not to stop taking it. For patients using glargine and considering switching to another form of insulin, the data in these studies make it unclear as to whether any one type of insulin increases the risk of cancer more than other types of insulin.”

The European Medicines Agency is also looking at the studies. The Agency’s Committee for Medicinal Products for Human Use will perform a detailed assessment of the studies’ results and any other relevant information. This review will also address issues, such as dose-response effects, the implications of the relatively short duration of the studies and influence of other factors on the risk of breast cancer and other cancers, such as age, body mass index, menopausal status, parity, and socioeconomic status.