Johnson & Johnson (JNJ:US)’s experimental diabetes pill may carry heart risks, U.S. regulators said in a review that threatens to delay the company’s first-to-market status for a new family of medicines.
Studies for the drug canagliflozin, which expels sugar in the urine after it’s filtered from blood by the kidneys, showed a potentially higher risk for heart events in the first 30 days compared with a placebo, Food and Drug Administration staff said today in a report. An FDA advisory panel is set to meet Jan. 10 to make recommendations to the agency on the drug.
The once-a-day pill is J&J’s effort to be the first to market with a new class of diabetes treatments known as SGLT2 inhibitors aimed at cutting side effects from current drugs. The drugs also are being developed by Eli Lilly & Co. (LLY:US), Boehringer Ingelheim GmbH, Bristol-Myers Squibb Co. (BMY:US) and AstraZeneca Plc. (AZN)
A delay to further assess risk “could erase its first mover advantage,” Lawrence Biegelsen, an analyst with Wells Fargo Securities in New York, wrote in a note to clients yesterday. “A first-to-market position is an important marketing advantage in this arena.”
J&J, based in New Brunswick, New Jersey, rose (JNJ:US) less than 1 percent to $71.41 at 4 p.m. New York time. Canagliflozin may generate $446 million in sales in 2016 if approved, according to the average (JNJ:US) of three analysts’ estimates compiled by Bloomberg.
The drugmaker has proposed marketing canagliflozin under the name Invokana for adults with Type 2 diabetes. It worked as well against diabetes in clinical trials as Januvia, Merck & Co. (MRK:US)’s second-best selling drug, and a generic treatment called glimepiride, FDA staff said.
“Results from our nine Phase 3 studies suggest that canagliflozin has the potential to help control blood sugar levels in a wide range of people with Type 2 diabetes while also offering other possible benefits like weight loss and reductions in blood pressure,” said Ernie Knewitz, a spokesman for Janssen, the J&J unit developing canagliflozin.
J&J submitted interim results of a study called Canvas on the medicine’s cardiovascular effects that showed canagliflozin also reduced blood pressure.
Regulators are scheduled to recommend whether to approve the drug by the end of March.
The studies reviewed so far showed that during the first 30 days of the cardiovascular trial, 13 cardiovascular events occurred on canagliflozin and one on placebo, according to the FDA staff. The drug raises LDL, or bad cholesterol, which may lead to the heart risk, despite favorable changes in HDL, or good, cholesterol, blood pressure and body weight, staff said.
“It is unclear whether this is a spurious finding or a true increased risk of early CV events,” staff said.
Additional follow-up may not address the signals of early heart risk and the FDA may decide to manage the harm through labeling, Biegelsen said today in a note. There is still a risk the FDA may wait until full data from the Canvas study becomes available in April, he said.
Diabetes is the seventh-leading cause of death in the U.S., according to the Centers for Disease Control and Prevention. The disease, defined by high levels of sugar in the blood, affected almost 26 million people in the U.S. in 2010, or about 8.3 percent of the population, the Atlanta-based CDC said.
There are 11 groups of diabetes drugs on the market, said Osama Hamdy, director of the obesity and inpatient diabetes programs at the Joslin Diabetes Center affiliated with Harvard Medical School in Boston. Most of the treatments stimulate the pancreas to secrete insulin or improve the body’s sensitivity to insulin, a hormone that helps control blood sugar.
SGLT2 inhibitors, like the one J&J developed, don’t cause low blood sugar or weight gain and because they’re the first to work on the kidney, they can be combined with any other diabetes medication for maximum effect, Hamdy said by phone.
“As a class of drugs available for Type 2 diabetes treatment, this is a welcome option,” the American Diabetes Association, based in Alexandria, Virginia, said in a statement.
Lilly, based in Indianapolis, and Boehringer Ingelheim, a closely held company based in Ingelheim, Germany, plan to apply for approval this year of their SGLT2 inhibitor empagliflozin, the companies said yesterday in a statement.
New York-based Bristol-Myers and London-based AstraZeneca are working to address FDA concerns with their product dapagliflozin, and may resubmit an application for review in the middle of this year. The FDA sought more data on New York-based Bristol-Myers and London-based AstraZeneca’s dapagliflozin after advisers determined the risks of bladder and breast cancer outweigh the benefits of the medicine.
J&J’s canagliflozin doesn’t show an increased risk of such malignancies, FDA staff said. The agency asked advisers to discuss the medicine’s potential to cause fractures, seen in animal studies, and adverse kidney effects.
Patients who used canagliflozin in clinical trials experienced genital fungal infections, increased urination and urinary tract infections, J&J said in a statement.
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