Three More Diabetes Drugs   (January 26, 2013)

Nesina, Oseni, and Kazano. Are these the names of the three billygoats gruff? Maybe the three bears that Goldilocks met? Or the three little pigs?

Nope, these are the names for three new “me-too” diabetes drugs, all based upon a newly-approved DPP4-inhibitor called alogliptin. Nesina is the name chosen by the manufacturer for alogliptin when sold as a single agent; Oseni is the name for alogliptin plus pioglitazone in the same pill; Kazano is the name for a combination pill containing alogliptin plus metformin.

Alogliptin, which was finally approved by the FDA yesterday for treatment of T2DM after being previously rejected twice, is the fifth DPP4-inhibitor to seek FDA approval, and the fourth to be approved by the FDA (sitagliptin/Januvia, saxagliptin/Onglyza, and linagliptin/Trajenta have been approved by the FDA, and vildagliptin/Galvus was withdrawn).

What’s different about alogliptin? Not much. It works to lower A1C the same way as the other DPP4-inhibitors: these drugs block an enzyme called DPP-4 (dipeptidyl peptidase-4), which causes levels of incretin  (GLP-1 and GIP) to rise, which causes insulin secretion to increase, which decreases blood glucose levels. But it did have a rocky road to gaining FDA approval: it was rejected twice, and the manufacturer now has several studies required as a condition of approval.

Quoting the FDA’s news release: “The FDA is requiring five postmarketing studies for Nesina (alogliptin alone): a cardiovascular outcomes trial; an enhanced pharmacovigilance program to monitor for liver abnormalities, serious cases of pancreatitis, and severe hypersensitivity reactions; and three pediatric studies under the Pediatric Research Equity Act (PREA), including a dose finding study and two safety and efficacy studies, one with Nesina as a monotherapy and one with Nesina and metformin.”

For the alogliptin/metformin combination (Kazano), “The FDA is requiring two postmarketing studies for Kazano: an enhanced pharmacovigilance program to monitor for liver abnormalities, serious cases of pancreatitis, and severe hypersensitivity reactions; and a pediatric safety and efficacy study under PREA. Kazano carries a Boxed Warning for lactic acidosis, a build-up of lactic acid in the bloodstream, associated with metformin use.”

And for the alogliptin/pioglitazone combination (Oseni): “The FDA is requiring an enhanced pharmacovigilance program for Oseni to monitor for liver abnormalities, serious cases of pancreatitis, and severe hypersensitivity reactions. Oseni carries a Boxed Warning for heart failure associated with pioglitazone use.”

It’s interesting that the manufacturer’s press release, Takeda Receives FDA Approval for Three New Type 2 Diabetes Therapies, NESINA (alogliptin) and Fixed-Dose Combinations OSENI (alogliptin and pioglitazone) and KAZANO (alogliptin and metformin HCl), somehow neglects to mention the FDA requirement for these further studies, although they are to be commended for including the boxed warnings, the Warnings and Precautions, Adverse Reactions, and Drug Interactions as part of the press release.

This trio of new drugs is nothing really exciting for people with diabetes or their physicians. I almost feel sorry for the drug company representatives who will be trying to pitch the idea of using these me-too drugs to busy physicians. After all, physicians already have eleven classes of diabetes drugs, and three other DPP4-inhibitors, to choose from.