FDA goes easy on Onglyza

FDA goes easy on Onglyza

Yesterday an FDA advisory panel went easy on Onglyza voting 14-1 in favor of adding information about heart failure risks to Onglyza’ s label. This outcome was the best possible result given the options available to the panel and could also be good news for Merck (NYSE:MRK) who will be releasing their cardiovascular data for Januvia in June.

Even with this positive result many are wondering whether this situation will prompt the FDA to make even more changes to how they approve new diabetes medications. As we have noted previously the FDA became hyper-sensitive to cardiovascular issues and diabetes drugs after the Avandia controversy. This controversy lead the agency to implement new rules for approving diabetes drugs, one of which was adding post-approval cardiovascular studies. What many are wondering today is should these studies be conducted prior to approval.

Frankly Diabetic Investor sees the FDA caught between the preverbal rock and hard place. Pharmaceutical companies are already complaining that the drug approval process takes too long and these additional studies, whether done prior to or after approval, add significant cost to drug development. Many researchers also believe that while these studies may be needed rarely do they yield conclusive results. This was an issue when the Avandia data was presented and remained an issue with the Onglyza data.

Yesterday the panel noted that the causes of death in the Onglyza studies were varied which muted their concerns that Onglyza was the direct cause. However this fact points to how difficult it is to draw a straight line between using a particular drug and an adverse cardiovascular event. This is not a simple math problem where 1 plus 1 equals 2 but a complex algebra problem with numerous variables. This issue was heighten during the Avandia controversy when different researchers drew very different conclusions from exactly the same data sets.

Yet given that the FDA’s mission is to ensure that a drug is not just effective but also safe they cannot ignore these studies. The questions they need to answer now are when these studies should be done and should there be a standard to meet before a drug is approved.  Should they decide studies need to be done prior to approval this would significantly slow down an already very slow drug approval process.

Additionally developing a set of standards for approval is equally problematic as even the experts cannot agree on what these standards should be. As we noted earlier a wide set of variables impact cardiovascular events and unlike glycemic control which can be measured by improvements in HbA1c, there is no universal agreement on which numbers the FDA should consider when assessing a drugs cardiovascular impact.

On the flip side however is the possibility that studies done after a drug has been approved will find that a widely prescribed drug does carry a significant cardiovascular risk. This puts the agency in the uncomfortable position of explaining why this drug was approved in the first place.

Adding even more fuel to this fire is the fact that it can takes years before adverse events appear. This happened with Avandia and Actos when after being on the market for nearly 7 years data found an increased risk of bone fractures.

So what’s the agency to do? How do they balance the need to get new and possibly better drugs to the market as quickly as possible against the need to make sure these drugs are safe? How do they insure that the drug development process, already a very expensive and lengthy process, does not become even more expensive and lengthy? As we have pointed out before the news rules implemented by the FDA has already created an environment in which drug companies are loathe to develop innovative new therapies due to the current regulatory environment.

Perhaps this issue really should be examined from a completely different perspective. We’re not sure when things changed but over the years somehow people started believing it was possible to develop drugs that are not just effective but devoid of any adverse events. Frankly this is not unrealistic, the goal is admirable but in reality a pipedream.

Still folks like Dr. Steven Nissen, our favorite crusading cardiologist, continue to live in fantasy land. They continue to believe that a drug should be pulled from the market when it causes 1 adverse event even when the drug is helping millions of patients. They see themselves as patient advocates when in reality they are just publicity seeking zealots who care more about getting on television than actually helping patients. Sadly these people have a voice and are listened to by the people who make very important and very difficult decisions.

Back when the Avandia controversy was in full force Diabetic Investor predicted that this one event would forever change how diabetes drugs are approved and how they are viewed even after they are on the market. Things have not changed for the better and one could easily argue they have gotten worse. All this because the good doctor got people to believe that it was possible to develop drugs which were 100% free of any adverse events. Thanks Steve sure hope you’re happy.