Testimony at FDA on Sotagliflozin to Help Manage Type 1 Diabetes

Stephanie Fox-Rawlings PhD, National Center for Health Research, January 17, 2019

Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Stephanie Fox-Rawlings. Our Center analyzes scientific and medical data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.

Improving glycemic control and reducing long term risks for microvascular harms for patients with type 1 diabetes are worthy goals that could greatly benefit patients. However, it’s not clear that this drug fulfills those goals.

If sotagliflozin is approved, it can be expected to be taken for many years or decades. It needs to provide patients with real, clinically meaningful benefits, otherwise patients unnecessarily risk side effects. The clinical meaningfulness is uncertain for some of the endpoints, including HbA1c, which were reduce 0.2-0.4% more with treatment than with placebo and the “net benefit responders” [percent of patients with HbA1c ≤7% without experiencing severe hypoglycemia or diabetic ketoacidosis]. We all know that a demonstrating a statistical improvement is not sufficient, that improvement must have a real impact on patients’ health, function, or quality of life.

In addition to the uncertain benefits, the studies demonstrate that this drug dramatically increases the risk for diabetic ketoacidosis – an approximately 8 fold increase over placebo. Patients chosen to participate in clinical trials are much more carefully selected and monitored than in medical practice. Thus the incidence of diabetic ketoacidosis could be much higher after approval if steps are not taken to ensure at least comparable levels of selection and monitoring. The company has proposed selection for patients that could carefully monitor and manage their treatments and diabetes as the primary method for reducing this risk. However, voluntary restrictions and labeling are often insufficient to limit prescribing to the appropriate patients.

The clinical trials included primarily young, white participants. Risks for diabetic ketoacidosis and severe hypoglycemia, as well as other aspects of diabetes, can differ based on demographic characteristics. Older patients also tend to experience more side effects and to have more comorbidities. With such a limited participant population, it is more difficult for patients and their clinicians to determine whether the drug is appropriate for them.

Please carefully consider and weigh how this drug could help and harm patients. Just providing new treatment options is not enough. New treatments must provide a real tangible benefit for patients without too much risk. If this drug is approved, the type and magnitude of the benefits and risks must be clearly communicated in the label so that doctors and patients can determine if the drug is appropriate for them. There must also be mechanisms in place to help reduce the risk for harm for patients who decide to try it and studied to determine if they work.