On January 26, pharmaceutical manufacturer Takeda announced the approval of its Type 2 diabetes drug, Nesina (generic name alogliptin) by the US Food and Drug Administration (FDA). It is the fourth drug in a class of medicines known as DPP-4 inhibitors, joining Januvia (saxagliptin), Onglyza (sitagliptin), and Tradjenta (linagliptin). Approved simultaneously with Nesina were the drugs Kazano (alogliptin and metformin) and Oseni (alogliptin and pioglitazone [brand name Actos]).
DPP-4 inhibitors work to lower blood glucose by blocking the action of an enzyme known as dipeptidyl peptidase 4, or DPP-4. DPP-4 breaks down hormones called incretins, which stimulate the release of insulin, slow stomach emptying, inhibit the release of glucagon (a hormone that signals the liver to release glucose), and enhance the survival and growth of the insulin-producing beta cells. With DPP-4 inhibited, the incretins have longer to carry out these actions.
Takeda first applied for approval of these medicines in 2007, a year before the FDA tightened its standards for new diabetes drugs; the agency told the manufacturer that it would have to comply with those new standards. Although Takeda resubmitted the application with expanded data, the FDA twice requested more information on the medicines, most recently in April 2012.
The safety and effectiveness of Nesina were established through 14 studies that involved a total of 8,500 people with Type 2 diabetes. Those taking Nesina experienced reductions in HbA1c (a measure of blood glucose control over the previous 2–3 months) of 0.4% to 0.6% compared to those on placebo (inactive treatment) after 26 weeks.
Kazano was shown to be safe and effective in four clinical trials involving 2,500 people with Type 2 diabetes. After 26 weeks, those taking Kazano had additional reductions in HbA1c of 1.1% over people taking Nesina and of 0.5% over people taking metformin.
Oseni, the first medicine in the United States to combine a DPP-4 inhibitor and a thiazolidinedione into a single tablet, was shown to be safe and effective in four clinical trials that included more than 1,500 people with Type 2 diabetes. Those on Oseni had additional reductions in HbA1c of 0.4% to 0.6% over people taking Actos alone and of 0.4% to 0.9% over people taking Nesina alone.
As a condition of the approval, Takeda is required to conduct five trials of Nesina once it is on the market including one focusing on cardiovascular events, as well as administering an “enhanced pharmacovigilance program” to monitor liver abnormalities, pancreatitis, and hypersensitivity reactions in people taking any of the three medicines. The manufacturer also must conduct three studies of Nesina in children: a dose-finding trial, a standard safety and efficacy study of the drug used alone, and a safety and efficacy study of the combination drug Kazano.
Nesina should be taken once daily and will be available in 6.25-milligram, 12.5-milligram, and 25-milligram doses. Kazano should be taken once daily and will be offered in doses of 12.5 milligrams of alogliptin/500 milligrams of metformin and 12.5 milligrams of alogliptin/1,000 milligrams of metformin. Oseni should be taken once daily and will be available in doses of 12.5 milligrams of alogliptin/15 milligrams of pioglitazone, 12.5 milligrams of alogliptin/30 milligrams of pioglitazone, 12.5 milligrams of alogliptin/45 milligrams of pioglitazone, 25 milligrams of alogliptin/15 milligrams of pioglitazone, 25 milligrams of alogliptin/30 milligrams of pioglitazone, and 25 milligrams of alogliptin/45 milligrams of pioglitazone.
The medicines are expected to hit the market in the summer of 2013.
“Controlling blood sugar levels is very important in the overall treatment and care of diabetes. Alogliptin helps stimulate the release of insulin after a meal, which leads to better blood sugar control,” noted Mary Parks, MD, director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research.
This medicine should not be used to treat Type 1 diabetes or diabetic ketoacidosis (a potentially life-threatening condition marked by a chemical imbalance in the body). The most common side effects in people using Nesina are stuffy or runny nose, headache, and upper respiratory tract infection. In people taking Kazano, the most common side effects are upper respiratory tract infection, stuffy or runny nose and sore throat, diarrhea, headache, high blood pressure, back pain, and urinary tract infection. And in those taking Oseni, the most common side effects are stuffy or runny nose and sore throat, back pain, and upper respiratory infection. Kazano carries a Boxed Warning for lactic acidosis (a serious condition in which lactic acid builds up in the bloodstream) associated with metformin use, while Oseni carries a Boxed Warning for heart failure associated with pioglitazone use.
For more information about Nesina, Kazano, and Oseni, read the article “Alogliptin Wins FDA Go-Ahead for Type 2 Diabetes,” or see the press releases on the Takeda Web site and the FDA Web site.