FDA knocks back Takeda's blockbuster hope TAK-721

Japanese drugmaker Takeda has suffered a blow to its late-stage pipeline, after the FDA rejected its marketing application for TAK-721, a drug candidate that is trying to be the first approved therapy in the US for eosinophilic oesophagitis (EoE).

Takeda said it had received a complete response letter from the US regulator that is asking for another clinical trial of the drug, which could set back the timeline for the programme considerably.

TAK-721 – provisionally known as Eohilia - is an oral suspension formulation of the well-established steroid drug budesonide that is designed to coat the oesophagus, localising its anti-inflammatory activity and minimising systemic absorption.

There were signs that all may not be well with the programme after the FDA said in July that it was extending its deadline for the review. Takeda acquired the drug as part of its $62 billion merger with Shire in 2019.

EoE is a chronic condition in which the oesophagus becomes inflamed as a result of an inflammatory reaction, generally caused by an allergy. It can cause the oesophagus to become narrower, making swallowing difficult, which can affect appetite. It can also lead to other symptoms like discomfort and vomiting.

Treatment at the moment is generally focused on identifying the allergen that causes the reaction and restricting it from the diet, but that can be hard to accomplish. Oral or topical steroids given by inhaler or in liquid form are also used, along with acid suppressing drugs to try to reduce symptoms.

TAK-721 is one of 12 "Wave1" pipeline drug candidates that have been held up by Takeda as potential blockbuster products, because they are either best-in-class or first-in-class therapies.

The company has had mixed results with them so far. In September it claimed approval for first-in-class lung cancer therapy Exkivity (mobocertinib), but that followed disappointments with NEDD8-activating enzyme inhibitor pevonedistat – which fluffed its lines in a phase 3 trial in myelodysplastic syndromes and acute myeloid leukaemia (AML) – and a delay for its dengue fever vaccine TAK-003.

"We are disappointed by the outcome of the FDA's review of TAK-721, and that EoE patients will still be without a treatment option that the FDA has approved as safe and effective," said Ramona Sequeira, head of Takeda's US business unit.

"Takeda is assessing the details of the CRL and evaluating a regulatory path forward," she added.