Vedolizumab

Vedolizumab ^?

Monoclonal antibody
Type	Whole antibody
Source	Humanized
Target	integrin α4β7
Clinical data
Trade names	Entyvio
Legal status	?
Identifiers
CAS number	943609-66-3 N
ATC code	L04AA33
UNII	9RV78Q2002 Y
Chemical data
Formula	C6528H10072N1732O2042S42
Mol. mass	146.8 kDa
N (what is this?)  (verify)

Vedolizumab (trade name Entyvio) is a monoclonal antibody being developed by Millennium Pharmaceuticals, Inc (a subsidiary of Takeda Pharmaceuticals) for the treatment of ulcerative colitis and Crohn's disease.^[1] It binds to integrin α₄β₇ (LPAM-1, lymphocyte Peyer's patch adhesion molecule 1).^[1][2] Blocking the α₄β₇ integrin results in gut-selective anti-inflammatory activity.^[3] It is marketed under the trade name Entyvio.

Discovery

The cell line used to develop vedolizumab was discovered by Dr. Andrew Lazarovits and Dr. Robert Colvin and was originally applied to anti-organ rejection strategies in kidney transplantation.^[4]

The research was conducted at Massachusetts General Hospital in Boston, MA. Dr. Lazarovits and Dr. Colvin's cell line was subsequently licensed to Millennium Pharmaceuticals of Boston for further development.^{[citation needed]}

Clinical trials

Vedolizumab has completed a number of phase 3 clinical trials^[5][6] for Crohn's Disease and Ulcerative Colitis (GEMINI I,^[7] GEMINI II,^[8] and GEMINI III^[9]) that demonstrate that vedolizumab is an effective and well tolerated drug.^[10][11] The results of the GEMINI 1 and GEMINI 2 randomized, placebo controlled multicenter trials of induction and maintenance therapy in Crohn's disease and ulcerative colitis have been published.^[12][13] An additional clinical trial, GEMINI LTS (Long-term Safety), is still being run.^[14]

Approval status

Takeda has filed a Marketing Authorization Application (MAA) in the European Union on March 7, 2013^[15] and a Biologic License Application (BLA) with the U.S. Food and Drug Administration on June 21, 2013 for both Crohn's Disease and Ulcerative Colitis.^[16] On September 4, 2013, Vedolizumab was given a Priority Review Status, which functions to expedite potential acceptance to market.^[17]

On December 9, 2013, the Gastrointestinal Drugs Advisory Committee (GIDAC) & Drug Safety and Risk Management Advisory Committee (DSaRM) discussed the Vedolizumab application for approval for both UC and CD under the trade name Entyvio.^[18] The voting went as follows: 1. Safety and efficacy data outweigh potential risks 21-0 2. 21-0 voted in favour of UC treatment 3. 20-1 voted in favour for CD treatment.^[19][20] Although GIDAC/DSaRM were a non-binding advisory committee, their opinions as field experts represent one of the last steps towards drug acceptance.

References