Fast Track designation comes about a month after dapagliflozin received another Fast Track designation for delaying the progression of renal failure and prevent CV and renal death in patients with chronic kidney disease
Dapagliflozin (Farxiga) has been granted a Fast Track designation from the US Food and Drug Administration for the reduction of risk for cardiovascular death or the worsening of heart failure in adults with heart failure with reduced ejection fraction (HFrEF) or preserved ejection fraction (HFpEF).
Coming on the heels of presentations at the major cardiology conferences, the designation is based on the DAPA-HF and DELIVER trials, which were both phase 3 clinical trials.
“This Fast Track designation for FARXIGA brings us closer to fulfilling our ambition to help prevent, treat and cure heart failure, and we look forward to working with the FDA to explore FARXIGA as a potential new treatment option for heart failure patients,” said Mene Pangalos, executive vice president, BioPharmaceuticals Research and Development.
DAPA-HF results, which were presented at ESC Congress 2019, revealed that 10 mg dapagliflozin reduced death and hospitalization by 26% in patients with heart failure and reduced ejection fraction with and without type 2 diabetes. DELIVER is currently ongoing and is examining dapagliflozin in patients with heart failure with HFpEF.
This marks the second Fast Track designation for dapagliflozin in as many months, with Fast Track designations previously awarded for delay the progression of renal failure and prevent CV and renal death in patients with chronic kidney disease. In a release, AstraZeneca noted that dapagliflozin is not indicated to reduce the risk of heart failure, cardiovascular death, or kidney disease.
In advance of the presentation of DAPA-HF results at ESC Congress 2019, Mikhail Kosiborod, MD, of Saint Luke’s Mid America Heart Institute, took part in a Q&A with MD Magazine® about the results of the study and its implications for heart failure patients.
MD Mag: What would it mean for patients if dapagliflozin were to receive additional approvals for heart failure?
Kosiborod: So, a couple of things. One is, what we know from the press release is that the trial met the primary endpoint, which was a composite of cardiovascular death or worsening heart failure (defined as either hospitalization for heart failure or urgent heart failure visit requiring intravenous therapy). And the trial was done in patients with and without type 2 diabetes. As of right now dapagliflozin is approved for glucose lowering in patients with type 2 diabetes.
Once the results from the trial are submitted to the US Food and Drug Administration, and if those results are compelling enough for the US Food and Drug Administration to grant a cardiovascular indication for dapagliflozin — which in this case would be an indication for heart failure — it could substantially change how dapagliflozin would be viewed as a therapeutic agent.
Right up until now, it was a medication to treat type 2 diabetes. With this development, if all of those assumptions that I just mentioned actually come true, if all of these things were to transpire, then dapagliflozin would no longer be just an agent for treating type 2 diabetes, but rather, an agent to treat heart failure.
Therefore, the potential application of this particular agent, dapagliflozin, would really evolve quite dramatically from being a glucose-lowering medication primarily, which is what it's currently approved for, to being a therapeutic agent to treat heart failure.
So, the key concept here is that you're stepping out - as far as the potential therapeutic uses of this agent - of the realm of it being a glucose lowering drug to being an agent to treat heart failure, potentially regardless of type 2 diabetes status or glycemic status of the patient. Of course, that has a number of potential implications to the whole new therapeutic area.
People with heart failure, have a very poor prognosis, as they have high risk of recurrent hospitalizations, death and progression of the disease, frequently leading to death, and also a very high symptom burden. And if in fact, once we see these results and if the FDA finds them compelling and it's indicated for patients with heart failure, this would be a very welcome development for patients with heart failure and reduced ejection fraction.
What are some of the other implications? Of course, while there are a number of different specialties that treat patients with type 2 diabetes — this may include internal medicine, family practice, primary care, endocrinology and cardiology for some patients, especially those with diabetes and established heart disease — but heart failure primarily is the domain of a cardiovascular specialist. So, that's another important facet. I think, if all of these assumptions come through, cardiologists will need to be a lot more actively engaged, potentially, in the actual clinical use of dapagliflozin than they have been so far.
MD Mag: With a Priority Review designation for chronic kidney disease recently announced, it appears dapagliflozin may also receive indications in other areas — what sets dapagliflozin apart from other SGLT2 inhibitors?
Kosiborod: So, dapagliflozin will be the first agent with a dedicated, heart failure trial completed in people with and without diabetes. So, at this point, that's the main distinguishing feature is that there will be outcome data for heart failure, regardless of diabetes status, with dapagliflozin in a large global trial that can truly informe clinical practice and possibly translate into a new indication. Again, we will see whether that happens.
With that acknowledged, there are other agents in the class that have ongoing heart failure trials, and that includes empagliflozin in the EMPEROR program, and sotagliflozin in the SOLOIST program, and SOLOIST is specifically in people with type 2 diabetes but the EMPEROR program includes people with without type 2 diabetes. So, there will be more data coming and that's for big outcome trials, there are also smaller trials looking at other important outcomes in patients with heart failure, both with reduced and preserved ejection fraction. Dapa-HF of course is specifically in patients with heart failure and reduced ejection fraction.
So, I think what sets dapagliflozin apart, as of right now, is that it's the first agent for which dedicated outcome trial data will be available in heart failure. But what we've seen so far in diabetes trials, is that there is quite a bit of overlap between different agents in the class in terms of cardiovascular and renal effects. They're pretty consistent.
There are a number of meta analyses that have now been published showing very consistent and robust benefits on prevention of incident heart failure primarily in patients who didn't have established heart failure at baseline — across several agents in the SGLT-2i class, as well as beneficial effects on the progression of diabetic kidney disease.
So there's quite a bit of overlap in the diabetes trials, and some of these effects appear to be be class effects. Now, whether same is going to be true in heart failure remains to be seen.
MD Mag: Is there anything else you wanted to add about dapagliflozin or SGLT2 inhibitors that we may not have touched on?
Kosiborod: It's a very exciting time for patients with heart failure, because as I said, it's a really deadly disease and has a very high risk of progression. These patients suffer from a very substantial burden of debilitating symptoms. So, having additional agents which appear to be efficacious in reducing important adverse outcomes in this patient population is really great news for the patients and for those of us who take care of them.