Clock Is Ticking For AstraZeneca

This morning Eli Lilly & Co . (LLY) released top-line results for the sixth AWARD study for their once-weekly GLP-1 dulaglutide. According to a company issued press release; “In the AWARD-6 study, once-weekly dulaglutide 1.5 mg achieved the primary endpoint of non-inferiority to once-daily liraglutide 1.8 mg, as measured by the reduction of hemoglobin A1c (HbA1c) from baseline at 26 weeks.”

In the AWARD-6 study, once-weekly dulaglutide 1.5 mg achieved the primary endpoint of non-inferiority to once-daily liraglutide 1.8 mg, as measured by the reduction of hemoglobin A1c (HbA1c) from baseline at 26 weeks. The drug is currently under review at both the FDA and EMA.

Also awaiting regulatory approval is Eperzan (albiglutide) from GlaxoSmithKline another once-weekly GLP-1. As with dulaglutide, GSK has a mountain of study data that shows Eperzan is safe and effective. Currently the only FDA approved once-weekly GLP-1 is Bydureon which is now wholly owned by AstraZeneca (AZN). While the drug seems to be gaining traction in the marketplace, sales so far have been disappointing.

Many attribute Bydureon’s lackluster performance to two keys items, the fact the drug must be mixed prior to injection and needle size; two issues which should be rectified when the Bydureon pen delivery system arrives, which according to Astra should be in the second quarter of 2014.

It was interesting that Lilly press release contained the following quote which is a clear swipe at Bydureon when Enrique Conterno, president of Lilly Diabetes stated; “If approved, dulaglutide would be the only GLP-1 agonist that is both once-weekly and ready-to-use.” Keep in mind that it wasn’t that long ago that Lilly was partnered with Amylin, the makers of Bydureon. A partnership that ended badly yet opened the door for Amylin to be purchased by Bristol Myers Squibb (BMY) with the help of Astra, only to see Bristol exit the diabetes business selling their stake to Astra.

It’s also pretty clear that GLP-1 usage is growing as evidenced by Victoza from Novo Nordisk (NVO) which for all practical purposes has exceeded expectations. Some may recall that Diabetic Investor thought Victoza would do ok until Bydureon came along as Victoza is a once-daily injection compared to Byetta which is injected twice-daily and was the only approved GLP-1 back when Victoza came to market.

We further speculated that Bydureon wouldn’t necessarily trump Victoza when it came to market until the more patient friendly pen delivery system became available.  What we didn’t expect was Lilly and Amylin going through a messy divorce, Amylin being sold to BMS/AZN, then BMS selling their stake to AZN. While the investment bankers loved this game of who owned Amylin, the fact is all this craziness has set back Bydureon sales.

Novo should actually send a thank you note to the folks at Lilly, BMS and AZN as Victoza’s success is due in large part Bydureon was a drug without a strategy. This game of musical chairs over just who owned Bydureon has cost the drug dearly. The question now becomes with Bydureon now solidly in the hands of Astra, at least for the moment, can the company get the pen delivery system to market and develop a cohesive strategy for the drug before GSK and LLY get their once-weekly GLP-1’s to market.

I'm not unconvinced that Bydureon hasn’t already suffered irreparable damage.  Normally its an advantage to be the first drug to market, especially a drug like Bydureon which had clear advantages over the existing GLP-1’s and had lots of time before any other once-weekly would be on the market.

Yet as so often happens in the wacky world of diabetes, where anything can and usually does happen Bydureon is quickly seeing its first to market advantage disappear and soon the drug will have a real fight on its hands. Although Diabetic Investor is skeptical that GSK is truly committed to Eperzan, we have no doubts that Lilly is very serious about dulaglutide. Lilly has the added incentive of proving to everyone that they didn’t make a mistake when they let Amylin go.

While Astra does have a decent diabetes drug portfolio, the portfolio is devoid of any insulin offerings which Diabetic Investor sees a serious handicap. Lilly has a long and established history in the insulin market and understands clearly the market for injectable therapies. The same is true of Novo who won’t go quietly into the night just because Victoza is a once-daily injection.

Like everyone else Novo understands that common sense would favor a once-weekly injection over a once-daily injection, yet they also know that all things being equal physicians are loath to switch patients off a medication that’s working. While Astra fumbles about, Lilly and GSK go through the regulatory process Novo continues to press ahead with Victoza.

The harsh reality is that Astra better get its act together in a hurry or the billions it spent to build a diabetes drug portfolio will go down as one of the worst investments in diabetes history, and that’s saying something given the wacky world of diabetes. Astra has a very narrow window of opportunity and while the pen delivery system will help somewhat it is no longer the silver bullet that will thrust Bydureon to blockbuster status.

The fact is market dynamics have changed dramatically since Bydureon’s approval and the many changes in the drugs ownership has stripped away any major advantages it once had. The clock is ticking for Astra.

David Kliff is publisher of the Diabetic Investor newsletter.