How a Pitch for Amylin's Diabetes Drug Byetta Actually Helped Its Rivals
Amylin Pharmaceuticals and Eli Lilly had a broad presence at the 70th annual American Diabetes Association convention held in late June. Unfortunately, clinical data presented at the conference for their once-promising type-2 diabetes drug Byetta served only to reinforce current physician prescribing habits -- which favor competitive agents from Novo Nordisk and Merck.
Amylin (AMLN) and Lilly's (LLY) presentations at ADA 2010 showed Byetta-treated patients were at no higher risk for renal or pancreatic problems than existing treatments -- including, Merck's oral Januvia and Novo Nordisk's in-kind Victoza injection therapy. The data helped allay outstanding safety concerns clouding all three drugs. Unfortunately, with no new sense of urgency for Byetta use --all Amylin and Lilly accomplished was to provide additional reasons to prescribe competitive agents Januvia and Victoza, as both challengers are easier to use for type-2 diabetes patients -- once-daily dosing versus twice-daily -- than Byetta, and offer lower incidences of nausea (reason most commonly given by patients who discontinue their Byetta therapy).
Launched in June 2005, Byetta sales peaked in 2008 at $678.5 million, after FDA warnings issued in 2007 that the drug was linked to kidney and pancreatic problems. Revenue for the first-to-market glucagon-like peptide (GLP-1) agonist (incretin mimetic) slid two percent last year and another 13 percent in the first six months of 2010. Byetta prevents the degradation of GLP-1, a gut-derived incretin hormone essential for sugar homeostasis.
Looking to rebuild physician confidence in Byetta, Amylin (AMLN) and Lilly (LLY) directed much of their lecture and lobbying time at the Orlando conference addressing safety and tolerability issues that have dogged twice-daily Byetta injection since its June 2005 launch:
- Notwithstanding an acknowledged higher risk with diabetes patients, an analysis of medical and pharmacy claims suggested Byetta-treated patients didn't have an increased risk of acute renal failure compared with patients on other type-2 diabetes treatment modalities.
- A retrospective observational analysis demonstrated treatment with Byetta posed no added risk for developing acute pancreatitis compared with other diabetes drugs, according to an analysis of medical claims data from pharmacy benefits manager Medco Health Solutions (MHS).
- Combination therapy with Takeda's Actos (pioglitazone) and Byetta caused significantly greater improvements in glycemic control and beta cell function compared to monotherapy with either drug, while preventing weight gain commonly observed with Actos alone.
Early on, Merck sales reps -- either directly or indirectly -- referenced Januvia as the "oral Byetta" - similar control of blood glucose, but with more convenient dosing, one pill a day without regard to meals versus twice-daily subcutaneous injections (one hour before morning and evening meals).
Although comparative trials have demonstrated slightly better glycemic control with GLP-1 agonists, the Merck reps have earned their sales bonuses: within one month of its October 2006 launch, Januvia accounted for 14 percent of all new diabetes prescriptions in the United States.
DPP-IV inhibitors lack the weight-reducing benefit (albeit weight neutral) found with GLP-1 agonists, but have a lower incidence of observed nausea and GI adverse events in clinical trials. 
Uptake for the Januvia franchise by both primary care physicians and endocrinologists shows little sign of abating: Januvia and Janumet (Januvia plus metformin) posted worldwide sales of $600 million and $218 million during the second quarter of 2010, representing respective increases of 30 percent and 41 percent over last year -- despite being dogged with similar kidney and pancreatic concerns.
Wolters Kluwer analyst Ben Weintraub noted in an October 2009 report, "What's Holding Back Byetta," that patients tend to stop using Byetta sooner than other diabetes medicines. Analyzing data on 1.5 million U.S. diabetics followed from January 2008 - January 2009, Weintraub uncovered the following persistency trend:
The average time on therapy for Byetta is 192 days, compared to 223 days for Januvia and 245 days for Janumet. Interestingly, the problem with Byetta is not an early drop-off, as might be expected due to nausea issues that generally resolve in the first couple months. Rather, the Byetta persistency curve follows other diabetes drugs until about six months, where it begins to drop off more sharply than the other drugs.Weintraub postulated that twice-daily injections could be a larger contributor to stopping Byetta use than GI adverse events. To ignore the role compliance plays in decision-making of harried primary caregivers attempting to see patients every 10 - 15 minutes, in my opinion, is to be "sincere and stupid" (to paraphrase Charles Kettering, head of GM R&D in its heyday).
Approved in early 2010, Novo Nordisk's (NVO) Victoza (liraglutide) has already surpassed Byetta, too, becoming the best selling GLP-1 agonist: By the last week of June, Victoza had already grabbed 26 percent of total GLP-1 prescriptions and 33.9 percent for all new patient starts in its drug class category. Victoza's biggest advantage over Byetta -- once-daily injection (irrespective of meals).
Vince Mihalik, VP - Sales & Marketing, told analysts on Amylin's second-quarter 2010 earnings call that new-to-brand data showed the GLP-1 class uptake had surpassed both glitizones (like Actos) and DPP-IV inhibitors, particularly among endocrinologists. However, primary caregivers had doubled their usage (and wrote 75 percent of total class scripts). Contrary to optimism expressed by Amylin management on Byetta's future, twice-daily Byetta injections will fall further behind once-daily GLP-1 agonists -- and DPP-IV inhibitors -- in coming quarters, as family doctors and internists prize compliance benefits even more than specialists.
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