Takeda Breathes New Life Into Entyvio With Preventative Use In Crohn’s Disease

Takeda is one of the longstanding leaders in the gastroenterology (GI) space, with a 30-year history of drug development, and 10 years of its flagship blockbuster α4β7 integrin antagonist therapy, Entyvio (vedolizumab).

The decade-old ulcerative colitis and Crohn’s disease therapy is still the jewel in Takeda’s sales sheet, growing 10% globally in its fiscal first half of 2024. Route of administration updates such as subcutaneous injection by pen is also invigorating US sales.

However, Takeda’s approach to GI goes “beyond products”, Marcelo Freire, the company’s therapy area head of gastroenterology, told In Vivo.

Global Biomarker Study

Key to this approach is a global study called the INTERCEPT project, a 60-month initiative that aims to identify clinically validated biomarkers that can predict the onset of Crohn’s disease.

While significant progress has been made in recent years with the advent of biologic therapies, Freire notes that there is still room for improvement. “This is about TA [therapeutic area] leadership, we are here to make sure that we can advance the field. In the last 20 years or so, biologics and advanced therapies have come to support patients that are in need, but we’re not there yet. We know that overall, around 30% to 50% of patients will achieve clinical remission at one year of treatment. So how do we solve that gap?”

That is where INTERCEPT comes in. By identifying biomarker signatures that can predict disease onset, the project aims to enable early intervention that could potentially delay or even halt the progression of Crohn’s disease. “Let’s keep in mind, 50% of CD patients will need surgery in 10 years. If we could intervene before that, and delay or potentially halt the progression of the disease, that would be transformative,” Freire emphasized.

The INTERCEPT project, funded by the Innovative Health Initiative to the tune of €38m ($39.5m) brings together a consortium of academic and industry partners, led by project co-ordinator Geert D’Haens of Amsterdam’s University Medical Center and Jean-Frédéric Colombel, director of the Inflammatory Bowel Disease Center at Icahn School of Medicine at Mount Sinai Health System in New York. Overall, 21 collaborative partners from Europe, North America and South Korea are involved.

The project aims to verify and clinically validate a panel of biomarkers and build a blood-based risk score that can identify individuals with a high likelihood of developing Crohn’s disease within five years after initial evaluation.

The project will recruit 10,000 healthy first-degree relatives of individuals with Crohn’s disease from seven European countries to further validate the biomarkers and risk score. From this group, 80 with the highest risk of developing Crohn’s disease will receive Entyvio to prevent full-blown disease from developing.

Due to come off patent in 2026, Takeda is confident that there will no biosimilar competition for Entyvio for at least three to four years, yet the use of Entyvio preventatively could be an excellent lifecycle management strategy.

The rationale for earlier intervention comes from findings that Entyvio yields better outcomes, and has a better safety profile, in early Crohn’s disease than in those with late disease. This was the finding of the LOVE-CD trial, initiated by a collaborative group of researchers from multiple institutions including D’Haens, INTERCEPT’s European head.

The LOVE-CD findings were presented at the United European Gastroenterology Week in October 2024. The study enrolled 260 participants with moderately to severely active Crohn’s disease. Among these, 86 had early CD (for less than two years) and 174 had late CD (for more than two years). All participants received standard induction and maintenance dosing with intravenous Entyvio 300mg up to week 52. The primary endpoint was clinical and endoscopic remission at weeks 26 and 52. This endpoint was met by 31% of the participants in the early CD group and 9% of those in the late CD group.

Exploring New Endpoints And Combinations

The company is excited about new endpoints beyond just clinical remission, such as endoscopic remission and transmural healing. “These studies are starting now,” Freire said, referring to the Phase IV VECTORS study (run by specialist GI contract research organization with Geert D’Haens as an advisor) that is looking at more comprehensive measures of disease control.

Combination therapy is another area of interest for Takeda, as they work to pioneer studies that leverage their flagship asset, in combination with other mechanisms of action. “Entyvio is considered backbone therapy,” Freire explained. “It’s not Takeda saying that. It’s the medical community, because of our efficacy and safety profile, that say it is a great partner for combination.”

The INTERCEPT study could bring about a new paradigm for treatment, said Freire, explaining that the study is “even more futuristic” than current studies. “When we talk about transmural healing or histological healing [with the VECTORS trial], INTERCEPT could show molecular healing. It is very ambitious,” he said.

“The more we understand about the progression of disease, the better. We have been, we are, and we will be in the GI field.”

Marcelo Friere

There is a lot to be gained from involvement in the study, beyond extending the marketability of Entyvio, said Friere. Having been active in the GI field for 30 years, Takeda’s GI team knows that the more it understands about the biology of Crohn’s disease, the more light is shed on why patients respond to a specific medication, and why others will not.

“The more we understand about the progression of disease, the better. We have been, we are, and we will be in the GI field. The totality of what is going to be obtained from this project will help us at many levels: drug discovery, the biomarker team, and drug development, so there’s a lot to be gained,” he concluded.