Despite the known dangers of its popular diabetes drug Actos, Takeda Pharmaceuticals is pushing ahead with the U.S. Food and Drug Administration (FDA) approval process to use the same main ingredient in another prescription medicine.
Pioglitazone is the active ingredient in Actos, which has been repeatedly linked to bladder cancer and other serious complications. Takeda wants to market another drug to treat diabetes that combines pioglitazone and alogliptin, and one that contains only alogliptin.
In April, the FDA refused to approve the alogliptin-only drug for treatment of type 2 diabetes, saying it needed more information on the medicine’s use in other countries. Takeda first tried for FDA approval of alogliptin several years ago, but the FDA then, too, asked for more data — that time on cardiovascular risks.
FDA Concerns over Actos
Now, it’s clear the FDA has concerns about both drugs. It issued a formal public safety alert in 2011, warning patients who take pioglitazone about the increased risk of bladder cancer — up to 40 percent higher, depending on how long the drug is taken. It also has required that the black-box warning — the strongest advisory the FDA can issue — on the drug packaging explain the risks of congestive heart failure. Actos also has been linked to macular edema and bone fractures in women.
Actos is part of the thiazolidinedione (TZD) family, and is used to help adults regulate their blood sugar when diet and exercise do not do enough. It makes cells more sensitive to insulin, which is the body’s hormone that stabilizes the blood sugar, or glucose. Actos can be taken in combination with insulin. The problems arise when Actos is taken for more than a year, which is not unusual in the treatment of type 2 diabetes.
Takeda Seeks Future Profits
Still, Takeda is persistently seeking approval of the two new diabetes medicines because they are seen as the next generation of diabetes treatments. Takeda loses patent protection of Actos, and subsequent brand-name drug revenues, this summer.
Takeda’s re-submissions include additional data from three phase-3 clinical trials involving more than 3,275 patients conducted at 1,384 centers worldwide, according to the company’s news release. The drug manufacturer reports the most common adverse events (greater than or equal to 5 percent and greater than placebo) reported in the alogliptin trials include headaches, urinary tract infections, cold symptoms and upper respiratory tract infections. In the human tests of combined alogliptin and pioglitazone, common adverse events were back pain, urinary tract infections, common colds and flu symptoms.
Takeda expects the FDA to complete this round of reviews within six months.