In an interview with PharmaShots, Nirav Desai, Global Clinical Development Lead at Takeda shared his views on TAK-721 data presented at ACG 2020 and its implications for patients and HCPs. The presentation includes post hoc analyses from a 12-week, randomized, double-blind, placebo-controlled Phase 3 clinical trial that investigated the safety and efficacy of BOS in patients with EoE 11 to 55 years of age.  Moreover, the presentation includes data from three additional studies, including real-world EoE analyses and a study on the pharmacokinetics of TAK-721. 

Shots:

• The new analyses showed an improvement in endoscopic and histologic response in patients underscore the encouraging potential of TAK-721 as a possible treatment for patients with EoE
• EoE is a chronic, immune-mediated, in?ammatory disease localized in the esophagus. Impacting nearly twice as many men than women, the chronic in?ammation of EoE can lead to a range of symptoms, including difficulties swallowing foods
• There is currently no FDA-approved treatment for EoE. BOS, also known as TAK-721, is Takeda's oral suspension formulation of budesonide, currently under investigation for the treatment of EoE in adolescents and adults.

Tuba: Can you briefly describe some of the key specialties about TAK 721 or Budesonide Oral Suspension (BOS)?

Nirav:  TAK-721 or budesonide oral suspension (BOS)  is a novel muco adherent topically active oral formulation of budesonide, designed specifically as an investigational treatment for eosinophilic esophagitis (EoE). The suspension is intended to treat the esophageal inflammation that is caused by EoE.  If approved, TAK-721 will be the first FDA-approved treatment for EoE. Further, the TAK-721 development program is the first and largest EoE Phase 3 clinical trial program in the U.S. to report results. 

Tuba: Please highlight the key findings / clinical endpoints for Budesonide Oral Suspension (BOS) that were presented during ACG Presidential Plenary Session.

Nirav: Results from ORBIT1, a multicenter, double-blind, parallel-group, placebo-controlled, induction study evaluating the efficacy and safety of TAK-721 (BOS) in adolescents and adults (11 to 55 years of age) with EoE, showed that TAK-721 (BOS) achieved coprimary and key secondary efficacy outcomes with statistical significance compared to placebo. Results on histologic, symptomatic, and endoscopic endpoints were presented during a Presidential Plenary Session of the 2019 American College of Gastroenterology (ACG) Annual Scientific Meeting.   The co-primary efficacy endpoints of this study were histologic response and dysphagia symptom response after an initial 12 weeks of therapy. The histologic response was measured as having a peak eosinophil count less than or equal to six eosinophils per high powered field, and dysphagia symptom response was measured as a greater than or equal to 30 percent reduction from baseline to final treatment as assessed by the Dysphagia Symptom Questionnaire (DSQ), a validated patient-reported outcome measurement tool. The key secondary efficacy endpoint included a change in DSQ score from baseline to final treatment. Additionally, the change in EoE Endoscopic Reference Score (EREFS) from baseline to final treatment period was evaluated as a secondary endpoint.   The majority of treatment-emergent adverse events (TEAEs) were mild to moderate in severity and incidence was similar between the TAK-721 (BOS)- and placebo-treated groups. The most common individual adverse reactions occurring in patients treated with TAK-721 (BOS) at a rate higher than placebo in 10 or more patients in ORBIT1 were nasopharyngitis, sinusitis, and esophageal candidiasis.  

Tuba: Which indications are mainly covered by BOS ? Please mention milestones it has cleared to date. 

Nirav: In December 2020, TAK-721 received Priority Review from the U.S. Food and Drug Administration (FDA) for the treatment of EoE. The FDA previously also granted both Breakthrough Therapy designation and Orphan Drug designation for TAK-721. If approved, TAK-721 will be the first FDA-approved treatment for EoE, and Takeda plans to use the trade name Eohilia (budesonide oral suspension). Currently, under investigation, TAK-721 has not been approved for use by FDA or other regulatory authorities, and these designations of Priority Review, Breakthrough Therapy, and Orphan Drug Designation don't guarantee that TAK-721 will be approved or become commercially available.

 Tuba: Can you please tell us about the importance of DSQ in this field of clinical study?  

Nirav:  The DSQ is a validated patient-reported outcome (PRO) that measures the frequency and severity of dysphagia symptoms and is the first daily symptom diary that has undergone structured psychometric validation specifically for EoE in both adolescents and adults. Takeda's ORBIT1 study was the first Phase 3 trial to measure an efficacy endpoint using this validated PRO measure (DSQ).  Dysphagia, or difficulty swallowing, is one of the primary EoE symptoms patients experience. The DSQ was developed according to the principles of the Final Guidance for Industry for Patient-Reported Outcome Measures and is now an established tool for dysphagia in this field of the clinical study.  

Tuba: Which indications in Gastrointestinal (GI) diseases according to you are the most untouched areas and need to be worked upon? 

Nirav:  Takeda sees an urgent need for improving patient care in gastroenterology. GI conditions can be chronic, painful, stigmatized and disruptive. Their impact is often under-appreciated. Takeda is working to shape the future of gastroenterology, to help restore life to living for people with GI conditions. This means pushing boundaries and working across modalities, taking on the most complex GI conditions and the most neglected patient needs, advancing original thinking and tackling barriers, to make a meaningful difference for patients. Our current therapeutic areas are Inflammatory Bowel Disease (IBD), Short Bowel Syndrome (SBS), and Motility and Acid-Related Disorders and our future pipeline interests include IBD, Immune-Related Diseases, Motility and Liver diseases. 

Tuba: Do you have a different strategy for the commercialization of TAK-721, since it will be the first of its kind?

Nirav: It's too early to comment on the commercialization of TAK-721, as it has not been approved for use by the FDA or other regulatory authorities.  What we can say is that with no FDA-approved treatments, there is still an unmet need for patients with EoE. Physicians and patients have limited choices for treating EoE symptoms, and patients often have to adapt how and what they eat. With the FDA's acceptance of Takeda's NDA for TAK-721, we are one step closer to potentially bringing patients and physicians a new treatment option that may help address the chronic, localized esophageal inflammation brought on by EoE.

 Tuba: Sanofi is evaluating Dupixent in EoE and has received the US FDA's BT designation for the same. How is Takeda's TAK-721 different or superior to Sanofi's Dupixent, and who do you consider as your competitors in the space?

Nirav:  At this time, we have not conducted any head-to-head studies as part of the TAK-721 clinical development program, so it would be inappropriate for us to comment on specific investigational therapies.  What we can do is provide more information specifically on TAK-721. Currently, there are no FDA-approved treatments for patients with EoE. TAK-721 is an investigational, oral suspension formulation of budesonide, which has been designed specifically for EoE. Takeda's clinical development program for TAK-721 rigorously evaluated the efficacy, safety, and tolerability of the formulation using histologic response, dysphagia symptom response, endoscopic assessment, and biopsy.

Tuba: Can you give an idea about the patients worldwide who are impacted by EoE and its complications?

Nirav: EoE is a chronic, immune-mediated, inflammatory disease that can cause damage to the esophagus and affects approximately one in 2,000 people in the U.S.Although the exact cause is unknown, EoE involves a complex interplay of genetics, environmental factors, immune system dysfunction, and atopy (the genetic tendency to develop allergies). The chronic inflammation of EoE can lead to a range of symptoms which can vary by person and age, and most often results in difficulty swallowing.If left untreated, inflammation ofEoE can worsen and narrow the esophagus

.Tuba: In near future, are you planning for any digital approach to deal with EoE?

Nirav: While EoE is increasing in prevalence in the U.S., it continues to be a challenge to diagnose as many of its symptoms are shared with other more common conditions. Takeda recently launched the digitally-based EoE program, one of the industry’s first-ever EoE education programs for healthcare professionals. With See EoE, Takeda is committed to bringing transformational change in EoE, by sharing a common definition of the condition, helping to increase its visibility, and working with community members to shorten the time to diagnosis and drive a sense of urgency to manage chronic esophageal inflammation.

Image Source: ENCORE Research Group

About Author:

Nirav Desai is a Global Clinical Development Lead at Takeda.

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