Enroute to Phase III, Teva and Sanofi bolster case for anti-TL1A drug

Teva and partner Sanofi presented new detailed results from their Phase IIb RELIEVE UCCD study, demonstrating strong and consistent efficacy for anti-TL1A biologic duvakitug across patient subgroups. The data, shared at the European Crohn's and Colitis Organisation (ECCO) conference on Saturday, set the stage for Phase III testing anticipated to begin in the second half of 2025.

The RELIEVE UCCD study is evaluating duvakitug in 240 patients with ulcerative colitis (UC) and Crohn's disease, who received one of two duvakitug doses (450mg or 900mg) or placebo subcutaneously every two weeks.

The new results build on data reported last December, which had shown that duvakitug met its primary endpoints in both UC and CD with "unprecedented" efficacy. Placebo-adjusted clinical remission rates at week 14 were 16% and 27% for patients with UC on low and high doses, respectively. Similarly, endoscopic response rates in patients with Crohn's were 13% and 35% higher than placebo for the two doses.

Subgroups, and more endpoints

Digging deeper into the data, subgroup analyses presented at ECCO revealed strong efficacy across patient populations. In UC, placebo-adjusted clinical remission rates in advanced therapy (AT)-experienced patients reached 22% (450 mg) and 29% (900 mg), while the rates for AT-naïve patients were 12% (450 mg) and 26% (900 mg).

For CD, placebo-adjusted endoscopic response in AT-experienced patients hit 7% (450 mg) and 44% (900 mg), with AT-naïve patients showing placebo-adjusted improvement of 25% with both doses.

The study also revealed benefits on additional endpoints. In UC patients, 70-81% showed clinical response (vs 52% on placebo), about half achieved endoscopic healing (vs 23%), and roughly a third showed histological-endoscopic mucosal improvement (vs 16%).

For the Crohn's cohort, 17-26% reached endoscopic remission (vs 9%) and over half experienced clinical improvement (vs 41%).

"Patients, many of whom have spent years in a recurring cycle of remission and relapse, have been waiting a long time for better options in treating ulcerative colitis," said lead investigator Walter Reinisch. "We're highly encouraged by the significant treatment response, compared to placebo seen in the study, both in advanced therapy naïve-and experienced patients."

Sanofi's head of R&D Houman Ashrafian, during the company's recent earnings call, said the data position duvakitug "pleasingly competitively" within the TL1A class, where several major pharmaceutical companies have made sizeable investments.

Notable moves in the space include Merck & Co.'s takeout of Prometheus Biosciences for $10.8 billion to get its hands on tulisokibart (PRA023), and Roche purchasing Telavant for $7.1 billion, bringing RVT-3101 into its pipeline. AbbVie also entered the fray last year, signing a licensing deal potentially worth $1.7 billion with China's FutureGen Biopharmaceutical to develop a next-generation antibody treatment for inflammatory bowel disease.

By contrast, Sanofi's collaboration with Teva came at a relatively modest upfront payment of €469 million ($491 million), which could turn out to be a bargain if duvakitug can maintain its competitive profile (see – Spotlight On: Sanofi's small anti-TL1A splash could pay big dividends).

Jefferies analysts noted in December that while tulisokibart and RVT-3101 (now known as RG6631) "are slightly ahead in development," duvakitug could potentially be "best-in-class given its subnanomolar affinity for death receptor 3 (DR3) over the decoy receptor 3 (DcR3), which could perhaps translate to better efficacy." The analysts project peak global sales of $5.3 billion for duvakitug.