Prometheus Biosciences, Inc.

Sanofi and Teva’s inflammatory bowel disease candidate could make €1 billion ($1.05 billion) a year by 2032, Leerink analysts said on Sunday. The blockbuster projection comes after the partners shared updated Phase 2b data from the anti-TL1A drug, dubbed duvakitug. The trial had a positive topline readout in December, earlier than was anticipated. But the new results, which were shared in a Saturday release , show “further evidence of efficacy and safety across all predefined subgroups,” the Leerink analysts said. Duvakitug produced responses in IBD patients who had previously been treated with advanced therapies (ATs) such as biologics, as well as those who hadn’t. In particular, 36% of AT-experienced ulcerative colitis patients who got the 900 mg dose achieved clinical remission, representing a 29% improvement over placebo. Just over half the AT-naïve patients also hit remission at that dose, yielding a 26% difference from placebo. In the Crohn’s disease cohort, 48% of AT-experienced patients given the 900 mg dose had an endoscopic response, representing a 44% improvement over placebo. Endoscopic responses were measured via the Simple Endoscopic Score for Crohn’s Disease, which considers ulcer size and surface area, among other factors. Clinical remission was measured per the modified Mayo Score, which looks at symptoms like stool frequency and rectal bleeding. The endoscopic response rate was 47% for AT-naïve patients on the same dose, good for a 25% difference from placebo. Sanofi and Teva plan to start a Phase 3 trial later this year. The French drugmaker spent €469 million ($500 million) upfront to license duvakitug from Teva back in October 2023. Teva could get up to $1 billion in milestones, split across $600 million for Phase 3 initiations and $400 million for launches. Sanofi will be responsible for commercialization in most markets, including the US, while Teva will lead in Europe, Israel and certain other countries. But the sell-side’s blockbuster forecasts should perhaps be taken with a grain of salt. Two other anti-TL1A drugs are ahead of duvakitug in the clinic and they offer less frequent dosing regimens — once every four weeks versus once every two weeks. These are Roche’s RVT-3101 ( acquired from Roivant) and Merck’s MK-7240, which it bought from Prometheus Biosciences in a deal worth $10.8 billion . Both drugs are already in Phase 3 development. Editor’s Note: This article was updated to clarify that RVT-3101 now belongs to Roche.

Teva and Sanofi announced positive mid-stage results ahead of schedule for their inflammatory bowel disease candidate as they look to keep pace in an anti-TL1A race with Merck and Roche. The duo’s duvakitug met the primary endpoints in a Phase 2b trial evaluating patients with ulcerative colitis and Crohn’s disease, two forms of IBD, Teva and Sanofi said Tuesday morning. In ulcerative colitis, 36.2% of patients taking a low dose of duvakitug and 47.8% of patients taking a high dose achieved clinical remission, compared to 20.45% of placebo patients at week 14. P-values came in at 0.05 and 0.003 for the low and high doses, respectively. In Crohn’s disease, 26.1% of low-dose duvakitug patients and 47.8% of high-dose patients saw an endoscopic response as measured by a scoring system for Crohn’s severity, compared to 13% on placebo (p-values were 0.058 for the low dose and <0.001 for the high dose). While 0.05 is typically considered the gold standard for assessing statistical significance, a Teva spokesperson said the Phase 2 study had a “one-sided test at a significance of 0.1.” The partners said duvakitug was “generally well-tolerated,” with similar rates of treatment-emergent adverse events occurring in the treatment and placebo arms. Sanofi put down €469 million ($500 million) upfront in a deal to co-develop and co-commercialize duvakitug with Teva in October 2023. The anti-TL1A contest also includes Roche, which put down $7.1 billion upfront in late 2023 to acquire Roivant’s subsidiary Telavant and RVT-3101. Merck is also a rival, following its acquisition of Prometheus Biosciences and its MK-7240 in a deal worth $10.8 billion. The duvakitug topline results came earlier than expected, due to “significant acceleration in patient recruitment,” Sanofi and Teva said back in July. As a result, they skipped an interim analysis which was originally planned for the second half of this year. Now, the partners said they plan to initiate a Phase 3 trial in 2025 in IBD “pending regulatory discussions.” A Teva spokesperson declined to share further specifics on the timing of Phase 3 initiation or the dose that will be taken forward. Each company will share the development costs globally, while Sanofi will lead Phase 3 development. Teva will lead commercialization in Europe, Israel and certain other countries, and Sanofi will take the commercial lead in North America, Japan and other parts of Asia, and the rest of the world. Editor’s Note: A correction has been made to reflect that Teva and Sanofi are studying duvakitug in inflammatory bowel disease, not irritable bowel disease.

Dive Brief:An experimental drug co-developed by Teva and Sanofi met its main objectives in a mid-stage clinical trial in inflammatory bowel disease, showing what the partners claimed to be best-in-class potential.Around half of people with ulcerative colitis who received a high dose of the drug, duvakitug, in a Phase 2 trial had their symptoms resolve after 14 weeks, versus just over 20% of those on placebo. A similar, roughly 48% of Crohns disease patients given a high dose of duvakitug experienced meaningful improvement on a measure of disease severity, compared to 13% of people on placebo, Sanofi and Teva said Tuesday.The companies didnt provide details, which will be presented at a medical meeting next year. Still, they said the drugs effects were consistent across subgroups and rates of treatment-related side effects were similar between both study groups. The partners intend to start late-stage development, pending discussions with regulators.Dive Insight:While the results are from a short Phase 2 trial, Sanofi and Tevas findings suggest duvakitug could be the most potent drug among a handful of closely watched antibody therapies for inflammatory bowel disease, or IBD, wrote Jefferies analyst Peter Welford.These drugs are aimed at a protein called TL1A, which regulates inflammation and fibrosis. Theyve caught the attention of pharmaceutical companies because of their potential to drive hard-to-treat cases of IBD into remission more powerfully and durably than existing treatments.Merck & Co. spent nearly $11 billion on Prometheus Biosciences in April 2023 largely to get a hold of a TL1A blocker that had shown promise in Phase 2 testing for instance. Roche followed with a $7 billion purchase of Televant months later and, earlier this year, AbbVie joined the chase, too.Duvakitug trails Mercks and Roches prospects; Merck has already initiated Phase 3 testing. But Tevas executives have long argued the drug could prove superior and, in Oct. 2023, Sanofi bought in, paying Teva $500 million to collaborate on development. The drug has since become more important to both companies, giving Teva known for its generics a chance at a branded blockbuster medicine, and Sanofi an opportunity to build investor confidence in its pipeline.While cross-trial comparisons can mislead, duvakitugs performance in Phase 2 testing appears strong. Mercks drug led to a placebo-adjusted remission rate of 25% in a Phase 2 trial in ulcerative colitis. Roches therapy was associated with an 18 to 23 percentage-point difference versus placebo in a similar trial, depending on the dose.Duvakitugs roughly 27% delta, and higher rates of disease improvement in Crohns disease, suggest the drugs different design versus its peers could perhaps translate to better efficacy, wrote Jefferies analyst Welford.If the magnitude of effect persists in the Phase 3 program, we believe we will have a differentiated medicine for IBD, said Sanofi R&D chief Houman Ashrafian, in the companies statement.Teva shares surged nearly 20% in early Tuesday trading, while Sanofis climbed by almost 5%.The programs advancement into Phase 3 will trigger a $600 million milestone payment from Sanofi to Teva. '