More Info Sought on Ulcerative Colitis Guidance
Several drug manufacturers are asking FDA for additional information on a draft guidance on clinical trial endpoints for ulcerative colitis. GlaxoSmithKline says the draft lacks guidance for sponsors on the desired definition of clinical response in the context of the proposed use of a modified Mayo score. “While the guidance is quite clear on the desired definition of remission based on the three domains of the Mayo score (stool frequency, rectal bleeding, and endoscopy score),” the letter says, “there is no guidance on the appropriate definition of clinical response based on these three domains. Nor is there a discussion of clinical response as a primary endpoint.”
Takeda says the guidance appears to be consistent with prior public discussions. The company says it looks forward to a guidance on Phase 3 study designs that will link with this guidance.
In its letter, Lilly notes that the guidance is intended as a starting point for continued dialog with interested stakeholders and asks that the agency consider further guidance on patient selection/target population and choice of comparator. “Lilly is interested in finding medicines that treat ulcerative colitis,” the letter concludes. “Because of the challenges with development in this area, we suggest that FDA continue to engage with the scientific community before the guidance is finalized.”
Novartis says it supports the agency’s guidance and asks that it be revised to discuss in greater detail treatment of patients who have been previously exposed to other therapies. “We believe it is critical to have clear expectations from FDA,” the company says, “because the mucosal healing in these hard-to-treat patients is very likely to be reduced. Because the definitions of response have been altered, new drugs that offer incremental, symptomatic benefits to patients who are without remaining treatment options may no longer be pursued by sponsors.”
The Celgene response says that it would be advantageous for global regulators to harmonize recommendations and identify the same scales and endpoints in studies to support global development programs.
Finally, AbbVie says it also is particularly interested in harmonization between FDA and the European Medicines Agency (EMA) on primary endpoints, induction and maintenance claims, and comparators. “We appreciate that the agencies may favor different approaches to these topics,” it says. “However, we respectfully encourage FDA and EMA to adopt similar approaches to facilitate timely new therapies reaching patients sooner than will occur when sponsors must negotiate with health authorities to conduct and analyze clinical trials distinctly designed to support the requirements of each health authority.”