Takeda tries again with subcutaneous Entyvio

More than three years after it was first rejected by the FDA, Takeda's subcutaneous (SC) formulation of Entyvio has been resubmitted as a maintenance therapy for ulcerative colitis.

The new formulation of the alpha-4 beta-7 integrin antagonist is intended for use after the current intravenous formulation of Entyvio (vedolizumab) is deployed as an induction therapy for the inflammatory bowel disease.

Entyvio has been on the market for moderate to severe UC in the US since 2014, both as induction and maintenance therapy, but Takeda wants to give patients the option of a formulation they can self-administer at home, rather than having to go to a clinic for an infusion.

Entyvio is one of the Japanese drugmaker’s top-selling therapies, and is on course to make $5.4 billion in the current fiscal year, but is facing an increasingly crowded market for UC therapies.

The SC version – which is already approved in the EU and Japan – could help Takeda fend off competition from newer moderate to severe UC therapies, including drugs like AbbVie’s Skyrizi (risankizumab) and Johnson & Johnson’s IL-12/IL-23 drug Stelara (ustekinumab), which are already available in SC form.

The category has also seen a clutch of new oral therapies, including JAK inhibitors such as AbbVie’s Rinvoq (upadacitinib), as well as Bristol-Myers Squibb’s S1P modulator Zeposia (ozanimod).

In December 2019, the FDA sent Takeda a complete response letter (CRL) that focused on the design and labelling of the injection device used in the product, rather than any issues with safety or efficacy in the VISIBLE 1 study, which showed the new version was as effective as the IV form.

It is not clear why it has taken so long to re-submit the application to the FDA, although Takeda said its resubmission contains “additional data collected to investigate the use” of Entyvio SC.

Takeda thinks FDA approval of the new formulation could help it hit the upper end of its peak sales forecast for Entyvio, which currently lies in the $7.5 billion to $9.0 billion range. It is anticipating a decision by the FDA before the end of the year.

“We have great confidence in the future of Entyvio SC and strongly believe that offering a SC formulation can help meet the varied needs of patients who live with moderate to severe ulcerative colitis, pending approval,” said Vijay Yajnik, Takeda’s head of US medical for gastroenterology.