NCHR’s Testimony at FDA Regarding Donislecel Treatments for Diabetes

April 15, 2021

Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Meg Seymour, a senior fellow at the center. We analyze scientific data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug or medical device companies, so I have no conflicts of interest.

Today, you are asked to discuss donislecel transplant treatments for brittle type 1 diabetes mellitus in adults whose symptoms are not well controlled despite intensive insulin therapy. We agree that safe and effective treatments are needed for the treatment of brittle diabetes, but we agree with the concerns of the FDA reviewers regarding the benefit-risk profile of the transplant treatments.

First, let’s talk about efficacy. As FDA notes, the applicant did not provide baseline data on the number of severe hypoglycemic events for 50% of the patients, which we agree makes it impossible to determine that transplant could have benefitted patients by reducing these events. Additionally, for the 50% of the sample where there actually are data on severe hypoglycemic events, 83.3% did not have any in the year prior to their first transplant, which FDA scientists point out means that any finding that patients did not have severe hypoglycemic events following their transplant would not represent a clinically meaningful improvement.

Another problem with the evidence is that 25 of the 30 patients had mild to severe anemia during the study. Anemia can falsely lower HbA1c, which affects the interpretation of HbA1c levels as an endpoint. FDA scientists note that this means there the data can’t demonstrate a clinically meaningful improvement in HbA1c.

It is important to keep in mind that both studies were single-arm, and were quite small, with a total of 30 patients between them. With only 6 men and zero people of color in the studies, it is not possible to generalize any of the findings to all adults with brittle diabetes. Even if the efficacy data were more persuasive, for example if in the future the company could provide more baseline data and longer-term outcome data, they only relate to White women. We would be very concerned if this treatment were at any point approved for patients who were not adequately included in the clinical trials.

Next, I would like to talk about safety. FDA notes in their clinical summary that during the clinical studies, different patients received the transplants at different time points, so a comparison of rates of AEs is not always possible, especially since there was no control group. We agree. And, due to the small size of the sample, it is difficult to compare the AEs between those receiving the treatment to those receiving a traditional pancreas transplant. Nevertheless, it is notable that only 30 patients experienced a total of 452 AEs in years 2 through 5 after the first transplant. 20% of patients experienced life-threatening events. For most patients, the assessment of safety was limited to 2 years. We agree with the FDA that given the potential risks of the transplants and the immunosuppression required to maintain viability, 2 years is not a sufficient duration for assessing AEs.

New treatments are needed and could be of great benefit for brittle diabetes patients. However, FDA approval should be based on evidence that a treatment is proven to be safe, to be effective, and to have a positive risk-benefit profile for patients. As a public health agency, it is FDA’s responsibility to only approve treatments shown to have a favorable risk-benefit profile, rather than approving a treatment for the sake of having more treatment options. We urge you to consider FDA’s strong concerns about efficacy and safety during your discussion later today.