In stunning reversal, Takeda snags FDA approval for once-snubbed Eohilia after 'significant grassroots support'

Eohilia, an oral suspension formulation of the corticosteroid budesonide, has surprisingly won over the FDA even after the drug’s developer, Takeda, had at one point abandoned the program following an FDA rejection.

Monday, Takeda announced the FDA’s approval for Eohilia for treating people 11 years and older with the inflammatory disease eosinophilic esophagitis (EoE). This makes Eohilia the first FDA-sanctioned oral med for the condition. In 2022, Sanofi and Regeneron’s injectable Dupixent claimed the title as the first FDA-approved therapy for EoE.

“As the treatment needs and goals of patients with EoE can vary, I welcome the flexibility that Eohilia offers as an oral medication,” Ikuo Hirano, M.D., from Northwestern University, an investigator in Eohilia’s clinical trials, said in a statement Monday.

Eosinophilic esophagitis is a chronic inflammatory disease that can cause painful damage to the esophagus, resulting in difficulty in swallowing. The condition affects about 1 in 2,000 people in the U.S., and Takeda has estimated Eohilia could reach $300 million to $500 million in peak sales.

Eohilia’s approval comes after some twists and turns. After a regulatory delay caused by additional data submissions, the FDA in late 2021 handed Takeda a rejection, blighting Eohilia’s prospect of becoming the very first official EoE drug.

After reviewing the FDA’s complete response letter, Takeda realized that the agency wanted data from an additional clinical trial, and that it could not take the drug any further.

“After a deep and careful assessment of the evolving treatment landscape in EoE, as well as considerations including operational challenges required for an additional clinical study, we could not justify further Eohilia development,” Takeda’s R&D chief Andy Plump, M.D., Ph.D., said during an investor call at the time.

Fast forward to October 2023, when Takeda suddenly said it had refiled Eohilia in the prior month. This time, Plump said “strong data and remaining unmet need in the U.S. spurred significant grassroots support” for Eohilia from the gastrointestinal and EoE communities.

Takeda worked with these communities to include additional data around Eohilia’s benefits in the resubmission, he explained.

According to Plump’s comment and Eohilia’s current label, Takeda apparently played down findings from a one-year maintenance study and instead focused on the drug’s 12-week data from a phase 3 and a phase 2 trial in its resubmission. Although that strategy got Eohilia the green light from the FDA, it also led to a restriction.

In Eohilia’s label, the FDA notes that the drug hasn’t shown to be effective for longer than 12 weeks. The label later points out that in a phase 3 extension study, continued treatment with Eohilia beyond 12 weeks didn’t show a statistically significant improvement versus re-randomization to placebo on some efficacy endpoints.

Still, the drug appears to be a good option for 12 weeks of treatment. Between the phase 3 and phase 2 trials, Eohilia, given at 2mg twice daily, respectively helped 53% and 38% patients achieve histological remission after 12 weeks of treatment, versus 1% and 2.4% for those who received placebo.

By comparison, Sanofi and Regeneron won Dupixent’s EoE nod with a 24-week analysis showing the weekly antibody drug led to histological remissions in 60% and 59% of patients in two parts of a phase 3 trial, versus 5% and 6% for the placebo group.

As for disease symptoms measured by the patient-reported Dysphagia Symptom Questionnaire (DSQ), Eohilia delivered 10.2- and 14.5-point improvements, compared with 6.5- and 5.9-point improvements for placebo. Results on the same endpoint for Dupixent were 21.9 and 23.8 points, versus 9.6 and 13.9 points for placebo.

Thanks to the approval, Takeda said it’s looking to reverse a previously recorded impairment loss tied to Eohilia’s rejection, but that it doesn’t expect the impact to be material.

Takeda’s business has come under pressure lately after the Japanese pharma’s blockbuster ADHD drug Vyvanse lost U.S. market exclusivity in August. Adding to the woes are a phase 3 flop for the company’s stem cell therapy Alofisel in complex perianal fistulas, the global market withdrawal of EGFR lung cancer med Exkivity, and the voluntary retraction of an application for the dengue vaccine Qdenga in the U.S.

The company has recently won two other FDA nods, one for colorectal cancer drug Fruzaqla, which Takeda in-licensed from Hutchmed a year ago; and the other for rare disease therapy Adzynma in congenital thrombotic thrombocytopenic purpura.