A heated day at the FDA and why a new drug class could bring us closer to personalized therapy.

Several weeks ago, I had the privilege of addressing an FDA advisory panel as it weighed the pros and cons of a new medication for type 2 diabetes. In this particular case, the advisory panel was effectively considering the merits of an entire drug class, since J&J’s Invokana (pronounced In-vo-CON-a; the scientific name is canagliflozin) is now set to be the first ever SGLT-2 inhibitor approved in the United States. SGLT-2 inhibitors improve blood glucose control by causing the kidneys to excrete any excess glucose in urine. The final 10-5 vote in favor of approval was an endorsement for Invokana from the panelists, especially since the most influential ones voted for approval; that said, there were a number of safety concerns raised during the discussion regarding certain groups of patients, particularly those with serious kidney disease.

As will probably not surprise you, Invokana – or any SGLT-2 inhibitor – is not going to be a perfect, all-inclusive solution that will radically change treating type 2 diabetes. Indeed, most FDA panelists felt that those with meaningfully impaired kidney function (more than 35% of people with diabetes aged 20 years and older have chronic kidney disease) should probably steer clear of using the drug. As a result, much of the FDA discussion was dominated by panelists’ concerns that Invokana would only work for some people. That’s certainly true; in this era in which ADA and major scientific leaders are asking for “personalized” care, that seems a reason to make sure it is prescribed carefully – but hardly a reason to lean away from approval, especially given that the majority of patients are not at the AACE’s A1c target of 6.5% and nearly half aren’t at the ADA target of 7%.

Last year’s ADA/EASD Position Statement on the treatment of type 2 diabetes placed a heavy emphasis on “individualizing therapy,” and we believe the SGLT-2 inhibitor drug class fits perfectly into that concept. If the diabetes community is indeed serious about finding the right treatment for each individual patient, then SGLT-2 inhibitors could plan an important role – those who are likely to benefit would be prescribed them, while those for whom SGLT-2 inhibitors represent an unacceptable safety risk wouldn’t use them. At issue is that we need more treatment options, given that roughly half of patients with diabetes in the US are not at an A1c less than 7% (the recommended goal from the ADA).

The challenge of achieving good glucose control translates directly into healthcare costs – this is becoming increasingly important as the top 1% of people with diabetes – about 200,000 people – has medical costs that average over $100,000 every year, while the top 0.1% each cost about $1 million every year, according to a conversation we had with the authors of a 2010 piece in Pharmacoeconomics by Elise M. Pelletier and her colleagues. This group desperately needs help, and they (and their healthcare professionals) need more tools at their disposable. SGLT-2s won’t help everyone in the costliest 1%, but drugs like these could help prevent people from developing costly related diseases. From our view, it’s all about staying healthy and treating to “success” and thinking creatively about what will keep patients focused on making sure their therapy and wellness decisions are working. If new compounds can help even a minority get and keep their glucose under control – or at least move to another therapy when the first therapy isn’t working anymore – the savings would be significant.

On the other side, it’s worth considering people who are just beginning their journey with type 2 diabetes. For most, metformin is generally regarded as the best therapy to use right at diagnosis – it is effective, has many years of safety data, and is potentially cancer-protective. But that’s only talking generally. Dr. Eric Topol of Scripps thinks that as many as one in five patients will derive no benefit from metformin due to genetic factors. This group might be better using a DPP-4 inhibitor (Januvia, Onglyza) or an SGLT-2 inhibitor. The problem is that most people never find out they’re genetic non-responders to metformin – the result is wasted time, discouragement, and exasperation with healthcare providers when their glucose and A1c levels fail to improve. Though there are currently no studies on genetic testing and drug responsiveness, we hope to see some done. If it were proven that taking a genetic test could help personalize therapy that would be great news, especially if payers started reimbursing for these tests. We learned at the recent JP Morgan Healthcare conference that there is now a company that offers such a test, 23andMe, and it costs just $99.

While healthcare providers are important to the success of any individualized therapy, it’s the patients themselves who are truly essential. That’s why we created our diaTribe Patient’s Guide to Individualizing Therapy, and it’s why we hope that, when the dust clears, SGLT-2 inhibitors and other emerging drug classes will have an important place in diabetes – we love classes that appear to be easier to take and easier to prescribe and, as long as safety holds, that seems true for this new class. Plus, of course, we love the rumblings that this may ultimately be useful for type 1 patients – we look forward to hearing the research on this front. There’s a right diabetes management combination for everyone, and the best way to ensure that remains true is to embrace new research, therapies, and technologies, even if they can’t solve everything at once.

Very best,

Kelly L. Close