All posts by Mary Jo Strobel

Response to FDA denial of topical oral viscous formulation of budesonide

Advocacy, What's New

In December 2021, APFED reported that the U.S. Food and Drug Administration (FDA) denied the TAK-721 New Drug Application, indicating the drug – a budesonide oral suspension –  would not be approved in its present form. According to the drug developer, Takeda, the FDA had also recommended additional clinical study to address their feedback.

TAK-721 is a novel, topical oral viscous formulation of budesonide, specifically formulated to treat localized inflammation in the esophagus caused by EoE. The drug sponsor has not made public the Complete Response Letter generated by the FDA regarding its application for TAK-721.  Given the pathway laid out by FDA regarding drug approval for EoE, the fact that oral budesonide has good safety profile and is approved for use to treat EoE in other countries and approved in the U.S. to treat other GI inflammatory conditions, APFED, along with other patient advocacy groups, sent a joint communication to the FDA to express our disappointment and confusion regarding the denial, and requested the FDA reconsider their decision regarding TAK 721 and make public the explanation for its decision not to approve.

We will continue to advocate and share information as it becomes available. In the interim, we encourage you to continue to share with us your experiences with mixing budesonide slurry for treatment of eosinophilic esophagitis, so that we may share compiled feedback with the FDA.

 

Industry News: Drug Development

Announcements, In the News, Research, What's New

 

FDA denies approval of TAK-721 (budesonide oral suspension) for EoE

Takeda, the pharmaceutical company developing TAK-721 (budesonide oral suspension) for the treatment of EoE, announced that the U.S. Food and Drug Administration (FDA) responded to the TAK-721 New Drug Application, indicating the drug cannot be approved in its present form.

Takeda reports that the FDA recommended an additional clinical study to help resolve their feedback.

“We are disappointed by the outcome of the FDA’s review of TAK-721, and that EoE patients will still be without a treatment option that the FDA has approved as safe and effective,” said Ramona Sequeira, President, U.S. Business Unit and Global Portfolio Commercialization, Takeda, in a press release issued by the company. “Takeda is assessing the details of the CRL and evaluating a regulatory path forward.”

 

Lirentelimab met histologic co-primary endpoints but missed symptomatic co-primary endpoints in both ENIGMA and KRYPTOS studies

Allakos Inc., a biotechnology company developing lirentelimab (AK002) for the treatment of eosinophil and mast cell-related diseases, reported Phase 3 data from ENIGMA 2 (a study of lirentelimab in patients with eosinophilic gastritis and/or eosinophilic duodenitis) and Phase 2/3 data from KRYPTOS (a study of lirentelimab in patients with eosinophilic esophagitis.

Both studies met their histologic endpoints, but did not achieve statistical significance on the patient reported symptoms endpoints.

In a company press release, Dr. Craig Paterson, MD, Chief Medical Officer of Allakos states, “Although the EGID results are surprising and disappointing, we will continue to analyze the data to understand the results and to determine the path forward for lirentelimab in EGIDs.”

 

Tezspire approved for severe asthma in ages 12+

Tezspire (tezepelumab) has been approved in the U.S. for people aged 12 years and older with severe asthma. Tezspire is the first biologic approved for severe asthma without phenotype (e.g., eosinophilic or allergic) or biomarker limitations. This therapy is also in development for other potential indications, including eosinophilic esophagitis. Learn more.

EGID Research at 2021 ACG Annual Scientific Meeting

Research, What's New

The annual scientific meeting of the American College of Gastroenterology (ACG) was held Oct. 22-27, 2021. The program featured lectures, posters, and case studies about a number of GI conditions, including EGIDs.

Several sessions were offered featuring experts that discussed pathophysiology, diagnostics and current management of EoE, as well as emerging treatments that may be the future of disease management. Experts also presented on the pathophysiology, diagnosis, and treatment of EGIDs below the esophagus, presenting the latest evidence for the efficacy of specialized diets and promising emerging pharmaceuticals that may soon alter the course of these diseases for many patients.  Other talks included special considerations for evaluating and treating EoE in children compared to adults, and predicting EoE treatment responses.

There were also many posters presented on EGIDs; below are are some highlights with links. For full details and poster access, visit acgmeetings.gi.org

Eosinophilic Esophagitis

  • Assessing the Influence of Tobacco, Alcohol, and Marijuana on the Development of Eosinophilic Esophagitis Access the poster.
  • Association Between Eosinophilic Esophagitis and Esophageal Dysmotility: A Systematic Review. Access the poster.
  • Development and Content Validity of the PROSE Daily Diary to Measure Dysphagia Episodes in Adults and Adolescents With Eosinophilic Esophagitis. Access the poster.
  • Development and Validation of a Simple Eosinophilic Esophagitis Severity Score That Is Predictive of Key Disease Parameters After Treatment With Topical Steroids. Access the poster.
  • Do Topical Corticosteroids Induce Histologic Remission and Improve Clinical Symptoms in Eosinophilic Esophagitis? A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Access the poster.
  • Duration of Symptoms Prior to Diagnosis Is Associated with Repeated Esophageal Dilations in Eosinophilic Esophagitis Access the poster.
  • Efficacy of Topical Corticosteroids in Achieving Histologic, Clinical, and Endoscopic Remission in Patients With Eosinophilic Esophagitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Access the poster.
  • Eosinophilic Esophagitis: Have the U.S. Guidelines Made a Difference for Inpatient Outcomes? Access the poster.
  • Eosinophilic Esophagitis National Trends: 2004-2014 NIS Data Retrospective Cohort Analysis. Access the poster.
  • Estimating the Indirect and Intangible Costs Associated With Eosinophilic Esophagitis. Access the poster.
  • Esophageal Eosinophil Count Does Not Correlate With the Endoscopic Reference Score Remodeling Subscore in Placebo-Treated Eosinophilic Esophagitis Patients in the Phase 2 Proof-of-Concept and Phase 3 TREET Studies. Access the poster.
  • Health-Related Quality of Life in in Adolescents and Adults With Eosinophilic Esophagitis in a Real World Setting in the U.S. Access the poster.
  • Increasing Prevalence of Eosinophilic Esophagitis in the United States from 2015 to 2018. Access the poster.
  • Long-Term Safety of Budesonide Oral Suspension for Eosinophilic Esophagitis: An Integrated Safety Analysis of Phase 1–3 Clinical Trial Data.Access the poster.
  • Patient-Reported Symptom Improvement Following Treatment With APT-1011 in Patients with Eosinophilic Esophagitis as Measured by the PROSE: Results from FLUTE, A Phase 2b Clinical Trial. Access the poster.
  • Patient Satisfaction and Adherence to Corticosteroids in Adolescents and Adults With Eosinophilic Esophagitis in a Real-World Setting in the U.S. Access the poster.
  • Patients With Eosinophilic Esophagitis and Gastrointestinal Symptoms May Have Eosinophilic Gastritis and/or Duodenitis, Not Associated With Peak Esophageal Eosinophil Count. Access the poster.
  • Perceptions of Disease Stigma in Adolescents and Adults With Eosinophilic Esophagitis in the U.S. Access the poster.
  • Post-Treatment Gene Scores Support Histologic and Endoscopic Response Thresholds in Eosinophilic Esophagitis. Access the poster.
  • Predictors of Clinical Response and Efficacy of Esophageal Dilation in Eosinophilic Esophagitis Patients Access the poster.
  • Quantitative Analysis of the Tug Sign in Adults: An Endoscopic Finding of Eosinophilic Esophagitis Access the poster.
  • Steroid Exposure in Patients With Eosinophilic Esophagitis (EoE) From the United States. Access the poster.
  • The Histological Scoring System and Endoscopic Reference Score Are Complementary Assessments for Characterizing Fibrostenotic or Inflammatory Phenotypes in Patients with Eosinophilic Esophagitis. Access the poster.
  • Topical Steroids for Eosinophilic Esophagitis: A Systematic Review and Meta-Analysis. Access the poster.

Subsets of EGID Below the Esophagus

  • Endoscopy and Systematic Biopsy of Patients With Moderate-Severe Unexplained Gastrointestinal Symptoms Compared With Healthy Controls: High Discovery Rate of Eosinophilic Gastritis and/or Eosinophilic Duodenitis. Access the poster.
  • Eosinophilic Colitis Accompanied by Synchronous Eosinophilic Esophagitis and Gastroenteritis. Access the poster.
  • Eosinophilic Esophagitis With Subsequent Eosinophilic Colitis: Keeping a High Index of Suspicion. Access the poster.
  • General Pathologists Do Not Routinely Evaluate Gastric or Duodenal Eosinophilia. Access the research.
  • Lymphocytic Variant of Hypereosinophilic Syndrome Presenting with Gastroenteritis. Access the poster.
  • Safety and Efficacy of Long-Term Treatment With Lirentelimab, A Monoclonal Antibody Against Siglec-8, in Patients With Eosinophilic Gastritis and/or Duodenitis. Access the poster.
  • Similar Efficacy of Lirentelimab in Patients With New vs Prior Diagnoses of Eosinophilic Gastritis and/or Duodenitis in a Randomized Trial. Access the poster.
  • Systematic Collection of Biopsies and Quantification of Eosinophils in Multiple High-Power Fields Is Required for Diagnosis of Eosinophilic Gastritis and/or Duodenitis. Access the poster.

 

>>> Learn more about the 2021 ACG Annual Scientific Meeting & Postgraduate Course at acgmeetings.gi.org.

 

Medical Foods Advocates Needed

Advocacy, APFED Blog, What's New

We invite community members to join us in advocating for the Medical Nutrition Equity Act.

Congress needs to hear from you!

APFED is an active member of the Patients & Providers for Medical Nutrition Equity (PPMNE) coalition. PPMNE is coordinating a week of actions June 14-18, including virtual meetings with members of Congress on June 15. We must send the message to Congress that it’s time to pass the Medical Nutrition Equity Act.

Join us! Learn more and register by May 31: https://nutritionequity.org/speakup2021/

 

Research Updates from ACG 2020 Virtual Annual Scientific Meeting & Postgraduate Course

APFED Blog, Research, What's New

The annual scientific meeting of the American College of Gastroenterology took place online, Oct. 23-28, 2020.

The program included lectures, posters, and case studies specific to eosinophilic gastrointestinal diseases. Below is a brief summary of some of the research presented at the meeting, and press announcements. To view the eposters, visit the ACG Poster Hall.

 

Assessing the Diagnostic Journey, Burden of Disease, and Treatment Patterns in Patients With Eosinophilic Esophagitis in a Real World Setting
Poster # P0852

A retrospective observational cohort study assessing EoE diagnostic journey, burden of disease and treatment patterns was presented as a poster. The average age of the patients in the cohort was 24.2 and roughly 65% were male.

The authors concluded that generally, symptoms and medicine usage by patients with EoE increased after diagnosis. The most common signs and symptoms from this cohort included dysphagia, abdominal pain and gastroesophageal reflux disease. The most commonly used off-label medicine before was proton pump inhibitors.

Patients consulted with multiple specialists and had substantial health care resource utilization (more than half of the cohort had ER visits and nearly 1 in 5 had inpatient admission).

Ellodi Pharmaceuticals announces favorable Phase 2b results of APT-1011, an oral disintegrating tablet of fluticasone propionate
S0345

Ellodi Pharmaceuticals announced results of APT-1011 (fluticasone propionate oral disintegrating tablet) in a Phase 2b clinical study known as FLUTE that addresses the maintenance of remission following induction in Eosinophilic Esophagitis (EoE). All APT-1011 dose arms showed clinically meaningful and statistically significant achievement of histological remission with reduction of eosinophil counts in the esophageal mucosa, compared to placebo, at 12 weeks. This was accompanied by symptomatic improvement, as demonstrated by reduction in patient-reported disease symptoms, such as dysphagia. These improvements were maintained over 52 weeks of treatment. APT-1011 was generally well tolerated.
Read more.

Results from Prospective Prevalence Study Indicate that Eosinophilic Gastritis and Eosinophilic Duodenitis* May be Significantly Underdiagnosed
Poster # P2797

Allakos Inc., a biotechnology company developing lirentelimab (AK002) for the treatment of eosinophil and mast cell-related diseases, announced results from a prospective study examining the rates of elevated eosinophil and mast cell levels in patients with chronic unexplained gastrointestinal symptoms or functional gastrointestinal disorders such as irritable bowel syndrome and functional dyspepsia. The results were presented at ACG as a poster authored by Dr. Kathryn Peterson of University of Utah, Dr. Robert Genta from Baylor College of Medicine; Drs. Amol Kamboj, Bhupinder Singh, and Henrik S. Rasmussen from Allakos; and Dr. Evan Dellon from University of North Carolina.
Among the findings, the researchers noted:
• 29% of patients entering the AK002 trial without an established diagnosis of EG/EoD were diagnosed with moderate-severe EG/EoD
• Most of the newly diagnosed EG/EoD patients had a previous history of GER/GERD, peptic ulcer disease, or a functional GI disorder
• Newly diagnosed patients had a similar symptom response to AK002 in ENIGMA as patients with an established diagnosis of EG/EoD
• Long-term treatment of AK002 in open label extension led to further improvement in symptoms and was generally well-tolerated

“These data suggest that EG/EoD may be more common than previously reported, and that EG/EoD should be considered in patients with chronic, moderate to severe GI symptoms,” the poster authors concluded. “Upper endoscopy with multiple gastric and duodenal biopsies may be indicated for patients with chronic nonspecific GI symptoms.”

*Eosinophilic duodenitis (EoD) is a newer and more specific term for eosinophilic gastroenteritis when the first part of the small bowel, the duodenum, is primarily involved.

View the Press Release

Phase 3 clinical trial post hoc analyses of Budesonide Oral Suspension (BOS) in patients EoE aged 11 to 55 years
Posters P0909 and P0878
Takeda Pharmaceuticals presented post hoc analyses from a 12-week, randomized, double-blind, placebo-controlled Phase 3 clinical trial that investigated the safety and efficacy of Budesonide Oral Suspension (BOS) in patients with eosinophilic esophagitis (EoE) 11 to 55 years of age.

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. Phase 3 clinical study results have shown TAK-721 to improve dysphagia symptoms, endoscopic appearance and reduce eosinophil counts in patients with EoE.

View the Press Release

Impact of Medication Compliance on Tissue Response to Proton Pump Inhibitor and Topical Steroid Combination Therapy in Children With EoE
Poster #P2529

A study presented at ACG sheds light on the relationship between pediatric adherence to PPI and topical corticosteroid therapy and the status of EoE and peak eosinophil count. Led by Dr. Girish Hiremath of Vanderbilt University Medical Center, the study authors also aimed to determine if any patient factors that were associated with complete compliance.
Among their findings peak eosinophil counts were found to negatively correlate with increasing medication compliance, and that the median peak eosinophil count was slightly lower in children with 100% compliance. They also reported that there was a significantly lower number of children with active EoE in the 100% compliance group (38%) versus those we had lower compliance (64%).

View Dr. Hiremath’s interview with HCPLive® about the research.

Registration for ACG 2020 is still open. For information on registration fees, visit https://acgmeetings.gi.org.