Novartis' NDA for its oral type 2 diabetes drug Galvus (vildagliptin) will remain in a holding pattern in the U.S. until the firm has a better idea whether it can gain FDA approval without excessive expenditures to gather additional safety data, executives said during the firm's fourth quarter earnings presentation Jan. 17.

Novartis said it is still in discussions with FDA over safety issues raised in a February 2007 "approvable" letter for Galvus and that a regulatory resubmission is not expected before 2010.

The company previously announced plans to conduct an additional safety study on the drug and resubmit the application for U.S. marketing in mid-2009 (¹ Also see "Novartis To Resubmit Galvus In Mid-2009" - Pink Sheet, 17 July, 2007.). FDA's concerns centered on patients with renal impairment who may be predisposed to skin lesions when taking the drug.

However, as talks with the agency progressed, Novartis found FDA expected a "very, very large study," Novartis Pharmaceuticals CEO Joseph Jimenez said. "But we don't want to invest in a very large study unless we have reasonable certainty that we would gain approval for Galvus in the U.S.," he maintained.

"So what we have decided to do is step back from the U.S. right now" and focus on ensuring Galvus "is a success in Europe, get additional [safety] data, and at some point we may go back to the U.S.," Jimenez explained.

Novartis Chairman Daniel Vasella added: "If we would get more clarity and, as Joe said, more confidence that with a study then afterwards we would sense openness and interest" from FDA, "then that would be a different story."

The drug is expected to launch in Europe in the first half of 2008 and is currently available in Brazil and Mexico. In November, after a pooled safety analysis linked the 100 mg once-daily dose to more-elevated liver enzymes, Novartis announced plans to discuss labeling changes with European authorities, recommending a 50 mg dose once or twice daily, which the firm hoped to take care of before launch (² Also see "Novartis Asks CHMP To Modify European Galvus Label To Recommend Lower Dose" - Pink Sheet, 6 November, 2007.).

Galvus is part of the dipeptidyl peptidase-4 inhibitor class. Currently, Merck's Januvia is the only DPP-4 inhibitor on the market, but Takeda recently submitted an NDA for its alogliptin, and Bristol-Myers Squibb/AstraZeneca are planning to file their saxagliptin this year as well (³ Also see "Takeda Files DPP-4 Inhibitor NDA, Poised To Best Bristol/AstraZeneca, Novartis In Race For Second To Market" - Pink Sheet, 4 January, 2008.).

Novartis has hit the roadblock in the U.S. for Galvus at a time when generic competition is causing steep sales declines for some of its leading drugs. During the fourth quarter, U.S. pharmaceutical sales fell 21 percent due to generic competition for Lotrel, Trileptal, Lamisil and Famvir , the company reported.

Sales were also hurt by the decision to suspend marketing in March of the irritable bowel syndrome drug Zelnorm due to serious cardiovascular events. Declines in the U.S. business contributed to a 42 percent decrease in the company's overall net income for the quarter.

For the full year, U.S. sales for the antihypertensive Lotrel decreased by 45 percent to $748 million, Trileptal sales declined 6 percent to $692 million, and Lamisil revenues dropped 40 percent to $595 million.

Declines were balanced by the antihypertensive Diovan' s 16 percent gain to $5 billion in sales for the year and a 14 percent increase for the cancer therapy Gleevec (to $3.1 billion). Sales for the novel antihypertensive Tekturna , launched in March 2007, reached $40 million, Novartis said. U.S. approval of Tekturna HCT is expected early this year.

-Cathy Kelly (c.kelly@elsevier.com)

Galvus Won’t Proceed In U.S. Without More FDA Clarity On Prospects, Novartis Says

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