Takeda Pharmaceutical Company Limited received a Complete Response Letter from the US Food and Drug Administration (FDA) in response to the submission of a Biologics License Application (BLA) for the approval of an investigational subcutaneous formulation of Entyvio (MAB) for maintenance therapy in adults with moderate to severe ulcerative colitis (UC).
Takeda is assessing the details of the letter, gathering information needed to resolve the FDA’s questions, and will work closely with the FDA on a path to approval. In its letter, the FDA posed questions unrelated to the clinical data and conclusions from the pivotal trial supporting the BLA.
Since intravenous (IV) Entyvio was approved by the US FDA in 2014 for patients with moderate to severe UC and Crohn’s disease, clinical trials and other evidence have continued to support its well-established safety and efficacy profile. Entyvio IV has been granted marketing authorization in more than 60 countries, including the US and European Union; in the US more than 150,000 patients have used Entyvio.
“At Takeda, we know how important it is to provide physicians and patients with choices, and we continue to drive innovation and development to meet their needs,” said Asit Parikh, MD, PhD, head of Takeda’s Gastroenterology Therapeutic Area Unit. “We’re committed to the development of the subcutaneous formulation of Entyvio, and look forward to working closely with the FDA to determine next steps.”
Entyvio (vedolizumab) is a gut-selective biologic and is approved as an intravenous (IV) formulation. It is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal address in cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1). MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract. The alpha4beta7 integrin is expressed on a subset of circulating white blood cells. These cells have been shown to play a role in mediating the inflammatory process in UC and CD. By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.
Vedolizumab IV is approved for the treatment of adult patients with moderately to severely active UC and CD, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFa)-antagonist.