Link to Pancreatitis is Bound to Negatively Impact Byetta Sales

Implications: The recent publication of new cases of pancreatitis that are occurring in patients taking Byetta (exenatide) can't be good for Amylin/Lilly. While Byetta and investigational GLP-1 analogs are still very viable therapeutics for Type 2 Diabetes, prescribers will have to reassess the risk-benefit ratio for many patients given the new information. The long-acting form of Byetta (LAR) may suffer the most since its long half-life will make reversal of pancreatitis that much more difficult and may lead to additional damage.

Analysis: While Byetta (and other GLP-1 analogs) still offers promise for many Type 2 Diabetics, the recent appearance of acute pancreatitis at a seemingly higher frequency than previously thought will lead to a more cautious use of these agents. High-risk patients (those with morbid obesity, severe hypertriglyceridemia, and significant alcohol consumption, for example) will particularly be at risk. Diabetics as a group already are at increased peril of this potentially fatal disease.

The benefits of GLP-1 analogs, such as sustained weight loss, will still motivate many prescribers to use this class of drugs. However, they'll have to decide if the benefits still outweigh the risks with this new and potentially severe adverse drug reaction now more prevalent. Overall, the combination of twice-daily injections (for Byetta) and risk of pancreatitis will offer manufacturers of competing drug classes (notably DPP-IV inhibitors) more room for positioning with regard to safety and compliance.

Where I believe the most damage may have been done to Byetta is the LAR (long-acting release) formulation. Byetta LAR was a boon to the major objection of patients using exenatide - namely the need for twice-daily subcutaneous injections. By switching to a once-weekly administration, much of this issue would have been removed. Now, anyone at risk of pancreatitis likely won't get the chance to try LAR. With a therapeutic half-life measured in days rather than hours, if LAR leads to pancreatitis, there will be no way to limit damage by immediately removing the causative factor. Most physicians won't want to risk three or four days of potential damage in at-risk users.

Overall, my feeling is that Byetta will continue to be used, albeit in more limited patient populations. The big hit to the franchise may likely come when competing GLP-1 analogs hit the market, especially if they have marginally improved dosing regimens (once daily, for example) without days-long half-lives, or if they eventually demonstrate a reduced risk of pancreatitis. Of course, the FDA will raise the bar for approval on these agents now, and will almost certainly require a "black box" class warning regarding the elevated risk of pancreatitis.