FDA Grants Orphan Drug Designation to ‘1104, First-In-Class Peptide for Eosinophilic Esophagitis

The FDA has granted Orphan Drug Designation (ODD) to ‘1104, a first-in-class immune-resetting peptide (Revolo Biotherapeutics) designed to treat eosinophilic esophagitis (EoE). The ODD offers support in developing potential new medicines, treatment, and diagnostic tools to prevent rare conditions that impact fewer than 200,000 individuals in the United States.^1,2

Image credit: Matthieu | stock.adobe.com

According to a press release, ‘1104 was created from a natural immune-regulatory protein called mycobacterium tuberculosis chaperonin 60.1, that is connected in resetting the immune system to offer long-term remission for individuals with allergic diseases, like EoE and asthma.² Prior to this designation, Revolo submitted a request following the results from its phase 2a EoE study, then later submitted a revised request after finding positive results in another phase 2 study.¹

EoE is a progressive allergic inflammatory disease that causes difficulty swallowing, gastric reflux, chronic pain, and weight loss among children and adults, if left untreated. The study authors noted that the inflammation is caused by T-cells and mast cells associated with continued tissue injury.¹

The study authors noted that approximately 180,000 United States individuals have EoE and around 80% have other allergic conditions, as well. If EoE is not treated when first detected, it could cause thickening of the tissue of the esophagus, which can lead to severe symptoms.²

The designation was based on data from RVLO-121-04, a phase 2a randomized, double-blind, placebo-controlled clinical trial (NCT05084963) that assessed the efficacy, safety, and tolerability of ‘1104 among adults with active EOE. The study administered a proof of concept, 2-week, 3-dose regimen.^1,3

The results from the trial found that the patient-reported dysphagia median symptom scores (DSQ) improved with ‘1104 compared to the placebo, and lasted 4 weeks prior to the last administered dose. A reduction in eosinophils, CD4+, and CD8+ cells was also reported in the ‘1104 groups, as well as an increase in T regulatory cells in esophageal tissue and B regulatory cells in the blood^.1,3

“’1104 is a promising EoE therapeutic with a novel mechanism of action. Based on the proof-of-concept data from the phase 2a study, I am eager to see this molecule move forward into the next stage of development,” said Evan Dellon, MD, MPH, Gastroenterologist, Professor of Medicine and Adjunct Professor of Epidemiology at the University of North Carolina Chapel Hill, and Principal Investigator for the Phase 2a clinical trial, in a press release.¹

The study authors noted that because of the positive results in the phase 2a trial, a phase 2b trial is in the works to analyze ‘1104 at a higher dose and a longer period of therapy among adults with active EOE throughout this year.¹

“We are excited that the FDA has granted ODD for ‘1104 in EoE, as there remains a significant unmet need for new treatment innovations for people living with this disease,” said Woody Bryan, President and Chief Executive Officer of Revolo Biotherapeutics, in a press release. “We look forward to initiating a Phase 2b study of ‘1104 in EoE later this year.”¹

References

1. Revolo Biotherapeutics Receives Orphan Drug Designation from the U.S. FDA for its First-in-Class Peptide as a Potential Treatment for Eosinophilic Esophagitis. Revolo. News release. January 30, 2024. Accessed January 30, 2024. https://revolobio.com/2024/01/30/revolo-biotherapeutics-receives-orphan-drug-designation-from-the-u-s-fda-for-its-first-in-class-peptide-as-a-potential-treatment-for-eosinophilic-esophagitis/.
2. Product Dev Landscape ‘1104. Revolo. News release. Accessed January 30, 2024. https://revolobio.com/product-development-landscape-1104/.
3. Revolo Biotherapeutics Announces Additional Data from Phase 2a Trial of ‘1104 in Adults with Active Eosinophilic Esophagitis. Revolo. News release. July 18, 2023. Accessed January 30, 2024. https://revolobio.com/2023/07/18/revolo-biotherapeutics-announces-additional-data-from-phase-2a-trial-of-1104-in-adults-with-active-eosinophilic-esophagitis/.