Byetta 2.0

Traditionally in the drug business there is a huge advantage to being first to market with an innovative new therapy. However this is not always the case. A fact which should not go unnoticed by the folks at Novo Nordisk. Novo has bet the farm on their recently submitted oral version of semaglutide, which when approved will be the first orally delivered GLP-1. We have little doubt the FDA will approve the drug, but we have lots of concern that this drug will reach the lofty sales estimates produced by the analysts who follow Novo.

Just as a refresher we have no problem with whether the drug works, nor do have any concerns over possible side effects. Based on all publicly available data nothing has popped up that would provide cause for concern. Our concern centers around the drugs rather complex dosing regimen which if not followed to the letter renders the drug ineffective. Hence the reason we believe the drug will get off to a great start only to see sales slow once physicians and patients become aware of the dosing regimen.

This places Novo in a rather precarious situation as there is a high level of awareness about the drug but little is known about how its dosed. Nearly every physician we spoke with at ADA was aware of the drug and seemed to have a positive first impression. This isn’t surprising really as GLP-1 therapy is now well established and known to be effective. Yet we were surprised how few actually were aware of the dosing regimen and fewer still knew that if this regimen was not followed the drug didn’t work.

This places a heavy burden on Novo as how do they inform physicians of this dosing regimen without dampening enthusiasm for the drug. Management knows they will have the only orally delivered GLP-1 on the market, that they need this drug to be a major hit and they cannot afford to disappoint the street. Simply put this makes the initial launch of the drug critical for if they fail to get the launch right there is historical precedent that it will never recover.

Even better for Novo the historical precedent they can learn from comes from the GLP-1 arena. Although largely forgotten today Byetta the first GLP-1 to hit the market was in a similar situation. There was a high level of positive awareness in the medical community based on what was publicly known about the drug. Byetta also had the benefit that physicians were eager for new treatment options especially one that came with the additional benefit of weight loss. Yes there was some trepidation as there would be with any new class of drugs but overall Byetta was viewed in a positive light.

Amylin, the makers of Byetta also had the benefit of being partnered with Lilly who at the time wasn’t doing so well in diabetes. Simply put Lilly needed Byetta to be a hit as much or more so than Amylin did. Unseen however was the behind the scenes rancor between these two partners. There is no reason to get into all the gory details let’s just say this marriage was not exactly a match made in heaven. Amylin and Lilly was more like the battling bicker sons than Ozzie and Harriet.

Yet this rambunctious couple got a huge break just before Byetta was to hit the market. About the time Byetta was approved in late April of 2005, concerns were rising over the most popular diabetes drugs at the time Avandia and Actos. Thanks to the crusading cardiologist Dr. Steven Nissan these two drugs which were ruling the world were in trouble. Even better Januvia, a drug many saw as a competitor to Byetta wouldn’t be approved until October of 2006. Although Amylin and Lilly weren’t getting along that well the stars appeared to be aligning in their favor.

This made the initial launch of Byetta critical, as Amylin and Lilly knew other GLP-1’s were coming and Januvia was an oral, get off to a good start and they could own the GLP-1 category while fending off the arrival of Januvia. Unfortunately the animosity between Amylin and Lilly prevailed and the Byetta launch was a disaster. Although sales eventually recovered it was too little to late as Victoza came along and the rest as they say is history.

Novo could be in the exact same situation as more than likely Intarcia will be resubmitting their exenatide micropump to the FDA. Get off to a good start with oral semaglutide and it can be open field running, stumble out of the gate and the door opens for Intracia. While the scenario is not exactly aligned with the Byetta launch the stakes are just as high. Novo in some ways has a bigger burden as so little is known about the dosing regimen and once known would likely dampen much of the anticipation.

Just as reps for drugs that were competing with Byetta were talking up the needle size for the Byetta pen, you can take it to the bank that Lilly reps selling Trulicity will mention this dosing regimen to physicians. Simply put Novo must get out in front of this issue or risk having the narrative defined for them. They also have the added hurdle of patient acceptance remember the physician only has to prescribe the drug the patient has to use it.

Based on what we know about patients we see this a much larger hurdle as we can envision patients asking to be taken off the drug even if its work. The fact is Trulicity has a patient friendly delivery system and only needs to be dosed once a week. While we would never say any injection is fun the Trulicity injection isn’t onerous and is just once a week. Once the Intarcia pump arrives that’s even better as once inserted the patient does nothing.

To us the GLP-1 story has always been about the fewer the better. Byetta was twice daily which was trumped by Victoza which is once daily which is trumped again by Trulicity which is once weekly which we see being trumped by Intracia which is inserted once and last for 6 months. Had the oral semaglutide come with a simple dosing regimen that would have trumped all the injectable and insertable versions as let’s face facts patients and physicians love pills.

But the fact is it’s not a simple dosing regimen and even worse it must be done each and every day. Had the pill only been taken once-weekly that would have been better, but this has to be done each and every day.

Novo has to be aware of this. They know what everyone else knows that therapy adherence or compliance or whatever the current PC term is for patients taking their meds is the key. That patients do not pay attention to what their physician says, that the moment they walk out of that office they forget 95% of what was said. They know that patients want simple. Yet like so many in this industry they also know how to screw up a simple peanut butter and jelly sandwich.

The story with oral semaglutide isn’t about being the first oral GLP-1 to market, the story will be about how simple is better than complex.