In a recent interview with PharmaShots, Andrea Stancati, Vice President, Head GI Global Medical Franchise shares his insights and highlights of Entyvio (vedolizumab)

Shots:

• The ongoing P-IIIb VISIBLE OLE study involves assessing of Entyvio (SC) in adult patients with UC or CD, following enrolment and participation in the VISIBLE 1 (UC) or VISIBLE 2 (CD) studies. Patients who completed the maintenance period up to 52wks. (randomized completers) or who achieved clinical response @14wks. (non-randomized 14wks. responders) after a third IV infusion @6wks. received Entyvio (SC, 108mg, q2w)
• Interim analysis from the VISIBLE OLE study showed long-term findings consistent with the known safety profile of vedolizumab with maintained rates of clinical remission and corticosteroid-free clinical remission
• Entyvio is the first maintenance biological therapy approved across the EU in both IV and SC formulations to treat moderately to severely active UC or CD. VISIBLE OLE results presented at UEG Week Virtual 2020 congress

Tuba:  Can we have a brief summary of Takeda's presentation at the UEG Week Virtual 2020 congress?

Andrea: During the UEG Week Virtual 2020 congress, we presented interim results from the VISIBLE open-label extension study on the long-term safety and efficacy of maintenance treatment with the subcutaneous formulation of Entyvio® (vedolizumab) in patients with moderately to severely active ulcerative colitis. Following two years of maintenance therapy with subcutaneous vedolizumab, long-term safety findings were consistent with the known safety profile of vedolizumab.

Additionally, patients continued to demonstrate clinical benefit from treatment, through the maintenance of clinical remission and corticosteroid-free clinical remission rates. These latest safety and effectiveness results are important as they provide further evidence that the benefits received from treatment with subcutaneous vedolizumab are sustained during long-term maintenance therapy.

Tuba :  Please tell us more about the mechanism of Entyvio (vedolizumab) and its uniqueness?

Andrea:  Entyvio is a gut-selective biologic which is approved in both intravenous and subcutaneous formulations.  It is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin on the cell surface of circulating T lymphocytes, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1) on the endothelial lining of capillaries. By blocking that interaction and inhibiting the alpha4beta7 integrin, Entyvio prevents T lymphocytes from going into the bowel wall and promoting and sustaining the cycle of inflammation that we see in patients with ulcerative colitis or Crohn's disease.

Tuba: Is Takeda evaluating the safety & efficacy of Entyvio in pediatric patients with UC & CD?

Andrea:  Yes. While Entyvio is not currently approved for use in people under the age of 18, we have undertaken several phase 2 and 3 clinical studies to understand the potential use of Entyvio in pediatric patients.

Source: New York Presbyterian

Most recently, in May 2020, we completed a phase 2 study (NCT03138655) that evaluated the pharmacokinetics, safety, and tolerability of vedolizumab in patients aged 2-17 with moderately to severely active ulcerative colitis or Crohn's disease. A phase 2b extension study (NCT03196427) is now in progress to determine the long-term safety profile of Entyvio, with results expected in 2021 and full completion in 2024. We recognize the considerable need to alleviate the debilitating symptoms experienced by children with inflammatory bowel disease and are working to optimize their care with new, targeted treatment solutions.

Tuba:  EU check, Canada check, Australia check, what are your plans for the geographic expansion of Entyvio (vedolizumab) SC formulation?

Andrea:  We intend to work with regulatory bodies globally to seek approval for the new subcutaneous formulation.

We are committed to providing physicians with treatment options that suit their patients' individual needs and preferences, whether that is intravenous or subcutaneous for maintenance therapy. Some patients may prefer a subcutaneous formulation as it allows flexibility, while others may favor intravenous administration due to regular touchpoints with a healthcare professional in a medical setting.

Tuba:  Are there any new formulations of Entyvio that Takeda is experimenting with?

Andrea:  The recent approval of the subcutaneous formulation of Entyvio has been a significant step forward in advancing care, offering another treatment formulation to suit the individual medical needs, preferences, and different lifestyles of patients. The patient experience is very important to Takeda, and our next focus is on evolving patient care in inflammatory bowel disease with a needle-free Entyvio delivery device. We are working with Portal Instruments on the needle-free device, which is currently in development.

Entyvio is the only gut-selective biologic that addresses inflammation specifically in the gut, significantly differentiating from all other non-selective therapies

Tuba: How is Takeda's Entyvio different from other competitors in this space?

Andrea:  Entyvio is the only gut-selective biologic that addresses inflammation specifically in the gut, significantly differentiating from all other non-selective therapies. It was the first maintenance biologic therapy approved across Europe in both intravenous and subcutaneous formulations to treat patients with moderately to severely active ulcerative colitis or Crohn's disease. Entyvio is now approved in over 70 countries worldwide, with more than 510,000 patient-years of exposure to date, providing extensive knowledge on the treatment's effectiveness and safety.

Tuba: As Takeda is committed to gastrointestinal innovation, what can we expect to see from Takeda to improve the QoL of patients with gastrointestinal diseases?

Andrea:  We've continued to demonstrate our patient-centric approach by further investigating and understanding the efficacy and safety profile of Entyvio. We have a number of important clinical studies still running, including in potential new patient populations, which will provide greater knowledge and enhance the body of evidence around the use of the therapy in inflammatory bowel disease. Furthermore, the newly approved subcutaneous formulation of Entyvio allows patients and healthcare professionals to better personalize care in line with which delivery method works best for the individual.

Longer-term, we are working with Portal Instruments on needle-free drug delivery options for patients who have problems with needles. These projects are a small part of our commitment to improving patient quality of life, aside from the research and development work we're doing to bring new therapeutic options to patients.

Tuba: What is Takeda's vision to restore the life of patients suffering from GI and liver diseases?

Andrea:  Patients are at the heart of our organization. At Takeda, we see no higher priority than closing the gap between the unmet needs and deserved solutions for those that battle these complicated conditions.

We believe that GI and liver diseases are not just life-disrupting conditions but diseases that can impact a patient's quality of life. Routines are interrupted, symptom management takes precedence, and the emotional pain can be just as present as the physical. Beyond a fundamental need for effective treatment options, we understand that improving patients’ lives also depends on their needs being recognized. Our approach is a simple one: if there is a need, we will seek to meet it; if there is a patient, we will strive to find a viable treatment solution; if there are questions, we will search relentlessly for answers.

Tuba: Can we have a comment on your rich and diversified pipeline targeting gastrointestinal diseases?

Andrea:  We are committed to providing novel medicines for GI and liver diseases globally. Through specialized and strategic in-house development, external partnerships, in-licensing, and acquisitions, we currently have several promising early-stage assets in development. We remain committed to delivering innovative therapeutic options for patients with GI and liver diseases.

Our core research focus areas in gastroenterology are GI inflammation, GI motility, and advanced liver diseases. In particular, we are making significant strides toward closing the gap on new areas of unmet needs for patients who have celiac disease, eosinophilic esophagitis, alpha-1 antitrypsin-associated liver disease, Crohn's disease, and acute pancreatitis, among others.

Our patient-centric philosophy begins with exploration as innovative as the treatments it leads to. To gain a greater understanding of the causes of GI and liver diseases, we collaborate with like-minded companies who are advancing the way patients are diagnosed and treated. One example of this is a new collaboration that has enabled us to obtain an intestine chip for research purposes that recreates the intestinal lining and maybe the gateway to new discoveries.

For more information on the Takeda pipeline, visit this link

Tuba: Is Takeda looking for any digital solutions for patients with IBD?

Andrea:  As part of our innovation in gastroenterology, we are exploring diverse ways to optimize the care and experiences of patients affected by inflammatory bowel disease. Our unique and holistic approach goes beyond providing patients with medicines by creating novel awareness campaigns and using medical education as a lever to empower patients. We believe that elevating gastrointestinal diseases starts with empathy. To make a real difference, we must understand how gastrointestinal diseases impact our patients' everyday lives.

An example of this is the creation of Takeda's digital disease awareness program called In Their Shoes. This immersive, award-winning simulation is built around mobile technology. It has been highly successful at helping others, including healthcare professionals, gain more knowledge by experiencing what it's like to live with inflammatory bowel disease and its complications. Over 2,000 participants from more than 30 countries worldwide have had the opportunity to simulate a patient's daily life via mobile app challenges, experiencing first-hand the emotional and physical burden of living with inflammatory bowel disease.

About Andrea Stancati:

Andrea Stancati is the Vice President and the Head of GI Global Medical Franchise at Takeda. He has joined Takeda in June 2018 as VP & Global TA Head Gastroenterology Medical Affairs. He served multiple global companies in his career including UCB, Novo Nordisk, Novartis & Roche

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