Nesina: Takeda trio enters a crowded diabetes field in Actos' wake

Project name: alogliptin; alogliptin + metformin hydrochloride; alogliptin + pioglitazone
Disease: Diabetes
Peak sales estimate: Once expected to hit $2.53 billion in 2016, the consensus peak estimate has slumped to $788 million.
Approved: Jan. 25
Company: Takeda

The Scoop:
For Takeda, Actos is a pretty difficult act to follow. The diabetes blockbuster brought in more than $16 billion in branded U.S. sales over its lifetime, accounting for half of the Japanese company's U.S. revenues and 18% of its worldwide sales.

But Nesina, approved a few weeks into 2013 along with two combos dubbed Kazano and Oseni, is trying to do just that. The FDA gave the diabetes drug the thumbs-up in January, less than 6 months after Actos generics spurred a serious sales dive. And while analysts don't expect the new family of drugs to fill Actos' giant shoes, the company is counting on it to help halt layoffs and curb the profit decline it expects through 2015.

While the FDA OK'd each drug as its own separate NDA, at the center of all three approvals is the active ingredient alogliptin, coined on its own as Nesina. Kazano and Oseni merge alogliptin with standard treatment metformin hydrochloride and with Actos' API, pioglitazone. All three are DPP-4 inhibitors, meant to stimulate the release of insulin after eating and in turn lead to improved blood sugar control.

Yet Takeda's drugs were hardly first to the DPP-4 inhibitor party, where Merck ($MRK) behemoth Januvia dominates the field. The $3-billion-plus-per-year drug leads a formidable class including Onglyza, born of a former joint venture between Bristol-Myers Squibb ($BMY) and AstraZeneca ($AZN), and Galvus, a contender from Novartis ($NVS).

Takeda can blame safety concerns for its latecomer status on the U.S. market. Cardiovascular scares have led the FDA to toughen its standards for diabetes treatments over the past few years, with controversial restrictions on GlaxoSmithKline's Avandia--later removed--serving as a prime example. In Takeda's case, U.S. regulators first denied alogliptin in 2009, citing potential cardiovascular risks and demanding additional data on the treatment. The company refiled in 2011 with interim cardiovascular safety data, but it wasn't enough to appease the agency.

Ultimately, it took 14 clinical trials involving about 8,500 Type 2 patients to get Nesina approved, along with a cardiovascular outcomes trial and four other postmarketing studies. Approvals for Kazano and Oseni did not come without their own concerns, either. Kazano bears a boxed warning for lactic acidosis, while Oseni displays one for heart failure associated with Actos.

But amid the heavy competition, Nesina should get a boost in China, where emerging markets expert Sanofi ($SNY) has signed on to assist with marketing. Under an April agreement, Takeda granted exclusive rights to Sanofi to copromote the drug for Type 2 diabetes, a growing health problem in China that represents a huge market opportunity; 114 million Chinese adults currently have the disease, with 40 million more expected to develop Type 2 over the next 20 years. And with its own diabetes lineup and a strong presence in China, Sanofi should be able to help Takeda make the most of that opportunity.

Still, the Nesina group will need some help if it's going to get Takeda back on track. The company had hoped some of that help would come from diabetes hopeful TAK-875, a GPR40 agonist designed to spur insulin secretion in the pancreas; Takeda had projected a Japanese approval for 2015, with the green light from the FDA a year or two down the road. But signs of liver toxicity in patients forced the Japanese pharma to toss the late-stage program at the end of December, leaving investors to wonder how it now plans to fill the Actos void. -- Carly Helfand (email | Twitter)

For more:
Takeda grabs long-awaited U.S. approval for diabetes drug Nesina
India yanks Takeda's Actos on safety concerns
FDA delays review of key Takeda diabetes drug, Actos combo
Takeda heads back to FDA with diabetes blockbuster hopeful

Nesina: Takeda trio enters a crowded diabetes field in Actos' wake