Thank you for the opportunity to speak today. My name is Dr. Megan Polanin, and I am a Senior Fellow at the National Center for Health Research. Our research center analyzes scientific and medical data and provides objective health information to patients, providers, and policymakers. We do not accept funding from the drug or medical device industry, so I have no conflicts of interest.
Patients with moderately to severely active ulcerative colitis need safe and effective treatments to help them better manage the disease. The goal is to improve quality of life, decrease hospitalizations, and reduce the risk of surgery and colon cancer.
We are glad that the FDA and the sponsor are working together to try to determine whether this drug is an effective and safe treatment for patients with ulcerative colitis. We agree with the FDA’s scientific assessment that there are concerns regarding this drug’s efficacy and safety for some dosing regimens and patient subpopulations. I will highlight our major concerns:
#1: We are concerned that the sponsor’s proposed dosing regimens of focus are based on exploratory analyses. For patients without adequate therapeutic response at 8 weeks and for those with a history of prior failure with a tumor necrosis factor (TNF) blocker, the sponsor proposes special dosing regimens. However, the sponsor did not use multiplicity controls, which are tools that prevent scientists from incorrectly stating that they have evidence that a drug works when it actually does not. Exploratory results cannot be relied upon to adequately support the sponsor’s proposed dosing regimens. The sponsor should be required to provide data ensuring that these proposed regimens are safe and effective before supplemental approval.
#2: We are also concerned that the sponsor’s studies include too few African American patients. As the FDA noted, less than 1% of participants in the overall safety analyses were Black, and only two Black patients were treated in the maintenance trial. In contrast, 1 in 4 patients at large treatment centers are Black. In addition to being disproportionately low, there were too few Black patients to have any confidence that this drug will be safe or effective for this subgroup. We strongly urge the FDA to delay a decision about approval until the sponsor conducts studies in representative patient populations who face significant disease burdens.
In summary, we are concerned that the clinical trial data do not adequately represent the real-world population of patients who will be likely to consider this drug. In addition, inadequate data prevent us from knowing whether the 10 mg BID dose will be safe or effective for patients who do not achieve adequate therapeutic benefit after 8 weeks of that dose. The same is true for the 10 mg BID dosing as continuous maintenance treatment for the subgroup of patients who have previously failed with a TNF blocker. Based on these concerns, we strongly recommend more persuasive data including a more diverse group of patients before making a decision about supplemental approval of the two proposed dosing regimens for induction non-responders and those with prior TNF blocker failure.
Thank you for the opportunity to share our perspective with you.
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The Gastrointestinal Drugs Advisory Committee voted 15-0 to include the additional dosing regimens on the product label. Read more about the meeting here.