Takeda’s push to lead the gastrointestinal (GI) field may have raised a few eyebrows at its inception, but the long-term strategy is now paying impressive dividends.
The recent EMA approval of the subcutaneous formulation of its Inflammatory Bowel Disease (IBD) drug Entyvio was another milestone, as well as an important boost for patients.
Takeda is now also focused on a needle-free jet injector application that would broaden choice for patients even further, a crucial advance, as the three million people in Europe living with Crohn’s disease or ulcerative colitis is expected to rise by around 25% by 2025, according to recent studies.
The success has been hard won. Entyvio, a monoclonal antibody, was shrouded with early theoretical safety concerns that clipped expectations until a suite of innovative and comprehensive trials reported positively and the company has amassed more than 500,000 patient years’ experience over the product’s six years.
“There were tremendous challenges at the start and at one point it looked 50-50 whether it would make it, but Entyvio is now approved in almost 70 countries and its uptake has been much greater than some analysts predicted,” said Asit Parikh, Takeda’s Head, Gastroenterology Therapeutic Area Unit.
“It has been a game changer for IBD patients and the EMA decision means that they have greater choice. They can continue on the intravenous (IV) treatment or chose subcutaneous treatment, which will help reduce unnecessary hospital visits and free up clinical time.”
Focused R&D strategy
“The odds were against Takeda because it had no heritage in IBD and there were several anti-TNFs on the market, so it is a testiment to the company’s commitment that we have achieved this.”
Parikh has good reason to celebrate, as he has been involved in constructing a potent GI unit that took its first steps with Takeda’s 2008 acquisition of US biotechnology company Millennium Pharmaceuticals for $8.8bn, when he was part of the team developing Entyvio.
It accelerated when President and CEO Christophe Weber took the helm in 2015, as the first non-Japanese leader of the 239-year- old company, and he continued a restructuring process that focused the company’s R&D strategy on cutting-edge, innovative approaches in GI, oncology and the central nervous system (CNS).
“We felt we could become the world’s leading company for GI, but in 2014 we only had molecule in the pipeline,” added Parikh, who is a gastroenterologist and physician scientist by training. “But we’ve had a lot of corporate backing and today we’ve got 12 molecules and have the strongest pipeline with the biggest potential impact on patients’ lives.”
Entyvio appears to be an emblem of Takeda’s GI journey, helping it not only win approvals but also frame an R&D ethos that is characterised by ambition and persistence. “The entire process has taught us the importance of thinking very differently, which matches very well with the way we’re structured right now,” adds Parikh. “The buzz was that Entyvio wouldn’t make it and there were tremendous challenges, but the uniqueness of its mode of action kept us going.”
Risk and reward
“We learnt lessons from this and the strongest one is that if there’s a true unmet need and you have a unique scientific advantage to leverage it, then this represents the ideal combination for de-risking drug development. What I always tell my teams is the riskiest thing of all in the business that we’re in is to take no risk.”
The excitement about Entyvio is founded on its specificity – selectively blocking a malignant pathophysiological interaction in the gut that causes IBD – and its unique targeting potential for other GI conditions.
Takeda’s strategy is to develop GI products that address the highest unmet needs, which includes projects across three novel platforms – gene therapy, microbiome and cell therapy. Projects that address gut inflammation beyond IBD are focused on coeliac disease, acute pancreatitis and short bowel syndrome. It also plans to achieve the first FDA therapy approval to treat eosinophilic oesophagitis, a chronic, allergic condition with little current respite.
“We have new drugs coming out in the next few years that will enable patients to cycle between different mechanisms and possibly even come back to the first one, quite possibly even if they lost response to it previously,” added Parikh. “This will help physicians take much better care of patients for something that is a lifetime disease.”
Takeda is also in collaboration with Portal Instruments, an MIT spin-out that is based close to its Cambridge, US, research HQ to produce a hydraulic jet injector that will give patients a needle-free option to take the drug. It is targeted for market approval in 2022.
The promise continues with a phase 3 trial deploying Entyvio as a support for stem cell transplantation cancer treatments that are vulnerable to graft v host complications, as lymphocytes thought to be problematic in IBD have been implicated in graft v host issues.
Chewing up enzymes
Takeda is also developing an enzyme that breaks down gliadin, a class of proteins in wheat and cereals that is damaging to coeliac patients. The product is entering a phase 2 study.
“Coeliac disease is well understood in Europe and has benefited from decades of research, but it is also on the rise in places where you might not expect. In India, for example, a recent survey highlighted that 1.5% of the 1.3 billion people that make up the population of India have immune reactivity to gliadin,” added Parikh.
“The enzyme effectively just chews up gliadin. We are really excited about it because we believe there is a clear medical need.
“Our motivation is clear. IBD has also been on the rise even in places where historically it didn’t have much of an impact, such as China, Japan, South-East Asia and India. It is a global issue and many of the patients are often diagnosed at a relatively young age, so they will need effective treatments for pretty much their entire life. We are completely focused on helping them.”
The GI building process has had to weather Takeda’s £46m acquisition of Shire that played out over the last two years, but Parikh comments: “Although they’re never easy, even when they go perfectly well, this one has gone extremely smoothly for us. We have been able to blend key elements and utilise a lot of talent from both companies.
“Every integration has some hiccups and there are always lots of meetings and presentation slides but the result has been really positive and it has been tremendous to see the team grow.
“There wasn’t a lot of pipeline conflict, as Shire was really known for rare diseases which Takeda had almost no presence in. There weren’t huge redundancies and from a scientific standpoint we weren’t stopping projects abruptly, which helped keep morale up.
“It has definitely strengthened us as a GI company and I don’t think there’s any other company that has so many approvals in the GI field.
“The last five years of growth has been built on partnerships. What we give and take from each is different, but it is essentially about Takeda and the partner each doing what they are really good at.
“I think there’s a really bright future for GI and our desire to be the world’s best motivates us every day.”
