Shire ($SHPG) has bought the rights to Pfizer’s ($PFE) experimental midstage inflammatory bowel disease drug PF-00547659 as it looks to shore up its own GI portfolio.
The drug has already been through Phase II testing in ulcerative colitis (UC) and Crohn’s disease (CD) and works as a fully human monoclonal antibody that is designed to directly target a gastrointestinal endothelial adhesion molecule known as mucosal addressin cell adhesion molecule 1 (MAdCAM-1), that binds to the α4β7 integrin on lymphocytes.
In the Turandot trial, the drug met its primary and secondary endpoints in patients with moderate to severe active UC who failed at least one previous treatment.
Those treated with PF-00547659 showed an increased rate of remission, response and mucosal healing at week 12, compared to those using a placebo.
In the Tosca study for Crohn’s, which only focused on safety, CSF lymphocyte cell count was not changed after treatment, and there was no evidence of infection.
Longer term treatment with PF-00547659 has also been assessed in the completed Opera II CD study, and is ongoing in the Turnadot II UC study.
Shire will now gain the global rights to all indications for PF-00547659 from Pfizer in a deal that was short on details, and without a financial breakdown.
In terms of the drug: In a nutshell, it targets white blood cell trafficking in the intestinal mucosa as a means of treating IBD. Key to this trafficking is the alpha4beta7 integrin protein carried on leukocytes and follows a similar mechanism of action as Takeda’s marketed UC drug Entyvio, as well as Biogen’s ($BIIB) Tysabri.
The emphasis on safety in the trials has come predominately from the experience with Tysabri, which can cause a fatal brain inflammation known as progressive multifocal leukoencephalopathy (PML). This has made some gastroenterologists wary of treatments sharing any aspect of its mechanism of action.
To help allay concerns, Pfizer has created its drug to work via a different factor, i.e., MAdCAM-1. Last year, Pfizer said after posting its Phase II data for the drug that unlike with Tysabri, it has no effect on immune surveillance in the central nervous system and does not bind to VCAM-1, another indirect target of Biogen’s that is likely to be involved in PML.
There are already a number of major blockbusters on the market for IBD, with AbbVie’s ($ABBV) Humira (which also has a number of other autoimmune disorder licenses) the cream of the crop, bringing in around $13 billion a year.
But many of these drugs are set to lose their patents in the coming years, with biosimilars waiting in the wings to decimate revenue--leaving the future marker for UC and Crohn’s uncertain.
Pfizer is seemingly set to concentrate its GI and autoimmune efforts on its new rheumatoid arthritis drug Xeljanz, as well as its other Crohn’s drug PF-04236921, an IL-6 currently undergoing testing.
For Shire, this slots into its GI pipeline and comes in the same week that it gained two FDA “breakthrough” tags for its rare GI disorder drugs SHP621 and SHP625. Shire also has approved treatments in the form of Vynase for binge-eating disorder and Gattex for short bowel syndrome.
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