Exploring the Impact of the Sotagliflozin Approval, with Deepak Bhatt, MD, MPH

On May 26, 2023, Lexicon Pharmaceuticals announced news many in the community had been waiting for, with bated breath, since Deepak Bhatt, MD, MPH, debuted the results of SOLOIST-WHF and SCORED trials at the American Heart Association’s 2020 Scientific Sessions: sotagliflozin had received approval from the US Food and Drug Administration for treatment of heart failure.

With approval for treatment of heart failure, the dual SGLT1/2 inhibitor becomes the first to receive approval in FDA history and represents the third agent boasting SGLT2 inhibition as a mechanism of action to be approved for heart failure across the spectrum of ejection fraction. Based on the data from SOLOIST-WHF and SCORED, sotagliflozin’s specific indication on the FDA labeling is for reducing the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure or type 2 diabetes, chronic kidney disease, and other cardiovascular risk factors.

Although a considerable portion of the fervor surrounding the agent and approval is driven by the rapid ascent of the SGLT2 inhibitor class into the guideline recommendations, with many expecting this role to expand further in the next iteration of heart failure guidelines. The remaining excitement is linked to the potential seen with SGLT1 inhibition. Like dapagliflozin and empagliflozin, Sotagliflozin proved benefit for heart failure and kidney outcomes in phase 3 trials but appeared to provide improved glycemic control at lower GFRs and also offered evidence of a beneficial effect on stroke and nonfatal myocardial infarction.

With approval in hand, Lexicon appears to be shifting its immediate focus to the commercialization of sotagliflozin, with the company announcing the expected availability of the agent for June 2023. However, given the evidence for potential benefit for major adverse cardiovascular events, and a number of trials conducted in type 1 diabetes, many within the healthcare community have already begun to look ahead to the future of the agent following the approval.

Ahead of the approval of sotagliflozin, our editorial team sat down with Bhatt, director of Mount Sinai Heart, to discuss the potential approval, what type of hesitancies might exist related to prescription, and more. The second half of the conversation with Bhatt focused on what is next for sotagliflozin and what a third SGLT2 inhibitors could mean for the community. This portion of the conversation the subject of the following Q&A.

Next Steps for Sotagliflozin

HCPLive: What do you think is next for sotagliflozin? Are there any further questions you would like to see answered in clinical trials?

Bhatt: It's a great question. I think there are multiple directions to consider for further trials, and I have many thoughts. However, given that it's a small company They need to generate revenue to fund large trials effectively. It's also crucial to recognize that generic SGLT2 inhibitors will be available in a couple of years. In my opinion, it would be wise to invest in clinical trials so that when that time comes, we won't be engaging in a purely theoretical discussion about whether sotagliflozin is potentially better or provides advantages over other SGLT2 inhibitors based on actual data. That would be the ideal scenario.

I believe conducting large-scale trials would be wise, although they can be costly. Additionally, I think it would be extremely valuable to continue investing in a distinct population from the one studied in SCORED. By comparing sotagliflozin versus placebo in a high cardiovascular risk population, separate from those with heart failure, we can determine if it reduces major adverse cardiovascular events. If the relationship I mentioned about the SGLT1 is proven true and relevant, it would be an excellent trial to pursue.

I believe more research in the context of type 1 diabetes would be beneficial. As you may know, the drug is approved for use in type 1 diabetes in Europe, although it was never commercialized for that purpose, unfortunately. Investigating its efficacy further in type 1 diabetes makes sense since we need more therapies for that condition. Additionally, studying the drug in patients with extremely low GFR, including those heading toward dialysis, could provide insights into its safety and potential benefits. Conducting meticulous studies in those areas could be highly useful.

These are some directions that come to mind, but there are still numerous areas where SGLT2 inhibitors can be explored. Ongoing trials of dapagliflozin and empagliflozin in acute coronary syndrome patients with or at high risk for heart failure are particularly interesting. We'll have to wait and see what those trials reveal. Apart from that, I'm not aware of any other significant trials involving SGLT2 inhibitors.

I mentioned earlier that generic versions of these drugs will become available soon, and typically, when that happens, companies tend not to invest in large-scale trials. Therefore, my hope is that sotagliflozin will pioneer and investigate some indications that might not otherwise receive attention. Nevertheless, we have to wait and see what the company can actually accomplish. Candidly speaking, I believe their ability to conduct large trials will depend, to a certain extent, on the drug's sales performance. I hope they can pursue such trials because I personally believe that the addition of SGLT1 inhibition complements the effects of SGLT2 inhibition.

HCPLive: How much of a benefit is it to clinicians and patients with heart failure to have a third agent with SGLT2 inhibition approved for treatment of heart failure?

Bhatt: These are 3 paradigm-shifting agents. As I mentioned before, each of them has compelling data. Engaging in a comparison of "which one is better" is missing the bigger picture.

I think the much, much bigger problem is that there is still a lot of patients with heart failure, either with or without diabetes, that are not getting any SGLT2 inhibitor despite the fact they have no contraindications. So, I think, from a quality improvement perspective, the focus is on that more so than which one, but, regarding cost, in general, the introduction of generic versions tends to lower prices. While branded drugs usually don't have a significant impact on costs, having a range of drug options is generally beneficial.

I think back to when there were multiple statins or ACE inhibitors that were coming out. For whatever reason, based on their interpretation of the data, one doctor might prefer one or the other. There might be some patient characteristics where one patient is better off with one or the other, or it might have to do with the labeling. There can be a variety of reasons, in addition to cost, that can affect the decision of which drug to use from a class of successful medications when there are some choices.

I think these are all good choices. I don't necessarily believe one is superior to the others. It's more about accommodating different patient needs and preferences. Much like when you saw new statins or ACE inhibitors came on board, it didn't completely replace older ones it was just a matter of different choices. I imagine that there will be negotiations behind the scenes as typically occurs in terms of trying to get lower costs of the drugs. I just hope if that happens, it's passed on to patients because that does not always happen, but assuming that happens then there's the added benefit that even prior to a generic world, there could be fewer costs.

Editor's Note: This transcript has been edited for grammar and clarity.

References:

1. Campbell P. FDA approves Sotagliflozin for treatment of heart failure. HCP Live. May 26, 2023. Accessed May 27, 2023. https://www.hcplive.com/view/fda-approves-sotagliflozin-for-treatment-of-heart-failure.
2. Campbell P. The prospect of SGLT1/2i in heart failure: Cardiologists await FDA decision on Sotagliflozin. HCP Live. May 26, 2023. Accessed May 27, 2023. https://www.hcplive.com/view/the-prospect-of-sglt1-2-in-heart-failure-cardiologists-await-fda-decision-on-sotagliflozin.