Third Time's the Charm: Bydureon Wins FDA Nod

By Jennifer Boggs
Managing Editor

Amylin Pharmaceuticals Inc. can (finally) put another check in the win column, with the FDA's approval of Bydureon, a once-weekly version of exenatide, a move that puts the San Diego-based biotech on solid footing for a lucrative ex-U.S. partnering deal – even a potential buyout isn't out of the question.

The label for the glucagon-like peptide-1 (GLP-1) receptor agonist came as expected, indicating the drug as an adjunct to diet and exercise for improving glycemic control in adults with Type II diabetes. The FDA asked for several postmarketing studies and a risk evaluation and mitigation strategy.

Bydureon is expected to be available to patients next month, at a cost of $323.44 per month.

Trading on Amylin's stock was halted midday Friday, but shares (NASDAQ:AMLN) were up 15 percent in after-hours activity.

Bydureon watchers were pretty confident going in to the Jan. 27 PDUFA date – Deutsche Bank analyst Robyn Karnauskas viewed approval as "highly likely" – but some doubts lingered, particularly given the agency's previous actions on Bydureon.

In March 2010, Amylin and partners Eli Lilly and Co. and Alkermes Inc. got a complete response letter citing outstanding issues regarding manufacturing and the drug's risk evaluation and mitigation strategy. Those were quickly resolved, but the FDA stunned the companies seven months later with a second complete response letter requesting a thorough QTc study to evaluate the risk of higher-than-therapeutic doses of Bydureon on the cardiovascular safety profile. (See BioWorld Today, March 16, 2010, and Oct. 21, 2010.)

The new drug application was resubmitted after the required study, completed early last year, showed that the drug did not prolong the corrected QTc interval in healthy individuals and showed no relationship between QTc interval and plasma exenatide concentrations.

But the delay did have its consequences. During the lag time, Indianapolis-based Lilly inked a deal with Boehringer Ingelheim GmbH on diabetes drug Tradjenta (linagliptin), which it decided to market with the same sales force that promoted the Amylin-partnered Byetta (once-daily exenatide). Amylin attempted to block Lilly from selling both drugs with the same team, even taking its decade-long partner to court. (See BioWorld Today, May 17, 2011.)

At the same time, some investors worried about Lilly's commitment to Bydureon in the event it gained approval of its own GLP-1 agonist, LY2189265, which analysts predicted could happen as early as 2013.

All of that led to Lilly agreeing late last year to exit the partnership. Under the terms, Lilly handed over all U.S. sales of the exenatide franchise to Amylin at the end of 2011 . Outside the U.S., the big pharma will continue selling the drug for a transition period – to expire Dec. 31, 2013 – during which Amylin will work to secure a new deal. (See BioWorld Today, Nov. 9, 2011.)

Extracting itself from Lilly, financially, involved a $250 million up-front payment from Amylin. The biotech also will owe future revenue-sharing payments equal to 15 percent of global net sales of exenatide products capped at $1 .2 billion. The good news is that the revenue-sharing payments aren't slated to start until late this year, and the firm could easily recoup those costs through another deal.

Piper Jaffray analyst Thomas Wei estimated that ex-U.S. rights to Byetta/Bydureon could be worth $1.3 billion. "We believe that we and the Street had previously underestimated the up-front infusion of capital that could be realized through a licensing of international rights," he wrote in a research report.

An acquisition also is a possibility, since a big pharma firm with a diabetes sales force could "extract cost synergies," maintained Deutsche Bank's Karnauskas, who previously named Merck & Co. Inc., AstraZeneca plc, Takeda Pharmaceutical Co. Ltd. and Roche AG as potential suitors.

In the meantime, Amylin will have the challenge of marketing both Byetta and Bydureon alone in the U.S., where it is up against heavy hitter Novo Nordisk A/S. The Bagsvaerd, Denmark-based big pharma sells Victoza (liraglutide), a once-daily GLP-1 agonist that has already taken a bite out of twice-daily Byetta. Sales of Byetta dropped about 11 percent between 2009 and 2010.

Yet even if Bydureon manages to hold its own against Victoza, there are other weekly GLP-1 drugs coming down the pike, including Syncria (albiglutide, GlaxoSmithKline plc and Human Genome Sciences Inc.), Lilly's LY2189265 and a weekly version of liraglutide from Novo Nordisk.

There's also the chance that Bydureon will cannibalize more of Byetta's sales, though Piper Jaffray analyst Ian Somaiya said the two drugs could grow independently thanks to Byetta's recent label expansion, which allows its use in combination with Lantus, a long-acting insulin product.

"We expect Bydureon to target primary care physicians that treat earlier-stage patients," Somaiya noted in a research report, adding that "Bydureon will be the first product detailed by the 650 reps from the exenatide business sales force, with Byetta in the second position."

In addition to the revenue-sharing payments due Lilly, Amylin also owes third partner Alkermes an 8 percent royalty on Bydureon sales. Waltham, Mass.-based Alkermes provided the Medisorb technology enabling the development of the long-acting version of exenatide.

Trading in Alkermes' stock also was halted Friday. Shares (NASDAQ:ALKS) were up 5 percent after hours.