What Do We Want Out of Our Diabetes Treatments?
We want our diabetes treatments to be effective, but we also want them to be safe, and it is up to the FDA to decide if the benefits of a given medication outweigh the risks. Consider insulin: if misused, it can kill you, but its benefits – it keeps all type 1 and many type 2 people with diabetes alive – far outweigh the risks. Most drugs, however, are not that clear cut. The benefits and risks can be blurry. Our concern, however, is that the pendulum has swung too far in favor of caution and safety at the expense of innovation. The consequences are serious. Much-needed new products are being delayed or are in danger of even being shelved entirely. The good news is that FDA will be considering these risk-benefit tradeoffs at a meeting in August, and you have a chance to make your voice heard.
Determining whether a new diabetes therapy should be approved has never been easy, but the turning point in this debate occurred in 2007, when the type 2 drug Avandia was implicated for apparently increasing the risk of heart attacks. To avert another Avandia, the FDA revised its guidelines so that drug companies would need to demonstrate cardiovascular safety in many cases before approval, adding huge costs to the process. (The cost of a CVD trial is $100 - $300 million.) The FDA tried to ease the burden by allowing the companies to submit so-called interim data, or data midway through the cardiovascular (also called CV) trial that demonstrated safety, and the companies could complete the trial after the drug was approved. But that is complicated, given the dynamics of how these trials are run. The participants in a CV trial are either taking the actual drug or a placebo; they don’t know which. But once the drug has been approved, the participants want that drug and are now motivated to abandon the CV trial. That’s logical behavior, but it negates the very costly study.
The result? Companies are giving up on diabetes. Bristol-Myers Squibb left diabetes entirely in 2013, and Genentech is out as well – two major causalities, no matter what anyone says officially, that we believe are at least in part a reaction to how costly it is to pursue diabetes compared to other areas. The CV trials can delay drugs (like degludec) and follow up drugs (IDegLIra) for years. That was for Novo Nordisk, which had the money to stay the course, but other companies don’t. Takeda has said it won’t develop its once-weekly DPP-4 inhibitor in the United States because the trials are too expensive, while delays with Sanofi’s GLP-1 agonist Lyxumia have slowed the development of entire new classes of diabetes drugs.
In sum, there are benefits to the trials – we are very interested in learning which drugs might be what’s called “cardio-protective” (that it would help reduce CVD complications) – but there are certainly costs as well, and we believe we are sacrificing innovation at the altar of safety. (And by the way, Avandia was ultimately found to be safe).
The FDA is holding a public hearing on August 11 to discuss how best to address interim data in its cardiovascular safety trials, and this is a real opportunity for us as a community to make our voices heard. Registration to attend the meeting is open until July 28; for those who can’t make it to Silver Spring, Maryland, you can submit a comment right here. At this link, click on "Submit a Formal Comment" in the top-right corner; comments can then be typed into the comment box or uploaded as an attachment. Every comment submitted before July 28 will be considered by the FDA, but you can submit all the way up to October 10. We would love to thank the FDA for giving patients and families and healthcare providers the option to comment. Read our response here! This is a complex issue, and it’s only part of a much larger question about how best we should handle the drug development and approval process. But for now, let’s tell the FDA that the status quo isn’t working. We also look so forward to following up November 3 in a conversation with FDA – read our new now next for more on this!
Kelly L. Close
Never miss an update by signing up here to receive free updates on future diaTribe articles.