Bristol-Astra Diabetes Drug Delayed by FDA Backed by Doctors as Needed

A diabetes pill that U.S. advisers said shouldn’t be sold because of cancer risks was cited last month by the Cleveland Clinic as a top 10 medical innovation for 2012, suggesting doctors expect the drug’s approval.

Dapagliflozin, made by Bristol-Myers Squibb Co. (BMY) and AstraZeneca Plc (AZN), uses a novel approach that blocks absorption of blood sugar in the kidney and expels it in urine. Doctors are eager to prescribe the drug because studies show it also reduces blood pressure, cholesterol and weight, causes of heart-disease that eventually kill most diabetics, said Steve Nissen, chief of cardiovascular medicine at the Ohio-based Cleveland Clinic.

It’s “a potentially important addition” to treatment options, Nissen said in a telephone interview. “My guess is that within the next year, this will get over the goal line. This is as good as anything we’ve seen.”

Advisers to the Food and Drug Administration voted against dapagliflozin’s approval in July, then asked New York-based Bristol-Myers and London-based AstraZeneca to submit more data on the drug. Last week, the FDA delayed its ruling on the treatment for three months, averting an outright denial.

Many analysts predicted the FDA would reject dapagliflozin after the panel vote, said Savvas Neophytou, an analyst at Panmure Gordon in London. It was a treatment “the market assumed was dead in the water,” he said.

The advisory committee voted 9-6 that the drug’s ability to reduce blood sugar levels didn’t outweigh the potential risk of bladder and breast cancer. There were nine breast cancers and nine bladder cancers among 5,478 patients taking dapagliflozin in clinical trials, compared with one breast and one bladder cancer among the 3,156 people in the groups that didn’t take the pill.

Doctors Skeptical

Doctors, though, are skeptical of the cancer risks because the number of affected patients was small, Nissen said. The cancers also appeared quickly, while most tumors take years to grow, suggesting the malignancies were developing before patients enrolled in the studies, he said. An analysis of results with more patients will help clarify the risk, he said.

“Nobody thinks this signal seen on breast cancer is real,” Nissen said. “The bladder cancer signal may simply represent ascertainment bias. Obviously, the issue will need ongoing surveillance, but it may turn out to be a false signal.”

Epidemic Levels

Diabetes is spreading at epidemic levels, according to the U.S. Centers for Disease Control and Prevention. One in 10 adults in the U.S., almost 26 million people, already have diabetes, while 35 percent have elevated blood sugar levels that puts them at risk for the condition, according to the agency.

Most people with the disease have the Type 2 form, which is linked to older age and excess weight. In Type 2, the body doesn’t make enough insulin to convert blood sugar to energy.

Dapagliflozin is the first in a new family of medicines called SGLT2 inhibitors to reach the FDA review stage. Pfizer Inc., Eli Lilly & Co., Johnson & Johnson, Eli Lilly & Co., Boehringer Ingelheim GmbH, and Astellas Pharma Inc. are among the companies pursuing SGLT2 inhibitors. Several competitors are in the final stage of testing, with sales potentially starting in the next two years.

The Cleveland Clinic placed dapagliflozin and its potential rivals on its annual list of “game changing” technologies that will alter medical care in the coming year. The awards were announced Oct. 5 at the clinic’s Innovations Summit.

Older drugs, such as metformin, lower production of glucose in the liver, while others stimulate the pancreas to make more insulin. Newer drugs, including Merck’s Januvia, Bristol-Myers’s Onglyza, Novo Nordisk A/S’s Victoza and Byetta, from Lilly and Amylin Pharmaceuticals Inc., use other methods to spur insulin production or reduce glucose levels.

Kidney Flush

Dapagliflozin is unique in that it helps the kidneys flush sugar from the body instead of trying to bolster insulin. And while some oral diabetes medicines have been linked to heart complications and weight gain, dapagliflozin has shown the opposite effect in studies, helping patients lose weight and lower their blood pressure. Patients getting the experimental drug also had fewer episodes of dangerously low blood sugar levels in studies that lasted up to two years.

“Now there is a new class of drugs ready for prime time,” the medical center said in announcing the list of top medical innovations. “These drugs represent a paradigm shift in diabetes treatment because they reduce blood sugar in a totally new way -- by causing it to be excreted during urination.”

The FDA’s move to delay a decision as the company gathers more data on its risks revives hope for approval, said Anthony Butler, an analyst at Barclays Capital in New York, in note to investors.

Additional Data

“There had been some suggestions that large-scale studies monitoring cancer risk as well as liver injury should be conducted prior to approval,” Butler wrote. “A request for existing data lowers the risk of additional clinical trials in our view.”

Bristol-Myers and AstraZeneca have started work on clinical trials investigating dapagliflozin’s impact on the heart, details that aren’t required until after a new diabetes drug reaches the market. As a result, they were able to give the FDA additional data from two studies on 1,800 patients with high cardiovascular risk, the companies said. More than 5,000 patients are enrolled in studies that are under way.

Because dapagliflozin offers a new approach, it can be added to other medications in patients struggling to control their diabetes, said James Young, chair of the Endocrinology and Metabolism Institute at the Cleveland Clinic, on Oct. 5.

“I’m hopeful and optimistic we’ll see it in clinical practice within the next year,” Young said. “I’m pretty bullish on this one.”

To contact the reporter on this story: Michelle Fay Cortez in Minneapolis at mcortez@bloomberg.net

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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