25% of Patients Achieve Endoscopic Remission in Phase 2a EMERALD-1 Trial for MORF-057

Bruce Sands, MD, MS

Credit: Alimentiv

Morphic Therapeutic has announced positive primary results from the phase 2a EMERALD-1 study evaluating the safety and efficacy of MORF-057 for adults with moderate to severe ulcerative colitis (UC).

Announced on September 22, 2023, the new data, which will be presented in a moderated poster session at the United European Gastroenterology Week 2023, showed 25.7% of treated patients demonstrated endoscopic improvement and 45.7% achieved clinical response at week 12.¹

“There are three desired attributes in an IBD treatment: favorable safety profile, meaningful clinical efficacy, and oral route of administration. Currently approved IBD treatments achieve at most two of these qualities and force patients to compromise; we need a new option to treat IBD patients that combines a high rate of clinical remission with a favorable safety profile in oral formulation,” commented Bruce Sands, MD, MS, chief of the Dr. Henry D Janowitz division of gastroenterology at Mount Sinai Health System.²

A selective, oral small molecule inhibitor of the α4β7 integrin, MORF-057 is designed to block the interactions between α4β7, a target for the treatment of inflammatory bowel disease (IBD), on the surface of lymphocytes and the mucosal endothelial cell ligand MAdCAM-1. This prevents inflammation associated with IBD by reducing lymphocyte migration from the bloodstream into intestinal mucosal tissues.¹

An open-label, multicenter, phase 2a trial, EMERALD-1 evaluated the efficacy, safety, and tolerability of MORF-057 in adults with moderate to severe UC. To be included in the study, patients were required to have symptoms of moderately to severely active UC for at least 3 months prior to screening, have evidence of UC extending at least 15 cm from the anal verge, and be bio-naïve or had an inadequate response, loss of response, or intolerance to other UC treatment.³

In total, 35 patients were enrolled in the main cohort and have been treated with MORF-057 100 mg twice daily at sites in the United States and Poland. The primary outcome of interest was change in the Robarts Histopathology Index score from baseline to week 12, while secondary endpoints included change in the modified Mayo clinic score, safety, pharmacokinetic parameters, and key pharmacodynamic measures, including α4β7 receptor occupancy and lymphocyte subset trafficking.²

Of note, participants in EMERALD-1 will continue for an additional 40 weeks of maintenance therapy followed by a 52 week assessment. After this assessment, all participants who complete the open-label treatment period will have the opportunity to continue their treatment in an optional 26-week long term extension study.³

According to the release, MORF-057 demonstrated a statistically significant reduction in the Robarts Histopathology Index score of 6.4 points (P = .002). Patients also had a 2.3-point reduction in modified Mayo Composite Score from baseline. Safety analyses indicated MORF-057 was well tolerated in EMERALD-1 with no safety signals or serious treatment-related adverse events observed.²

“We are emboldened by these positive results and excited to continue to enroll the ongoing EMERALD-2 Phase 2b study,” said Praveen Tipirneni, MD, CEO of Morphic Therapeutic.² “I couldn't be more thankful to these patients and investigators, and proud of our team for advancing MORF-057 much closer to our goal of providing a safe and effective treatment option for IBD patients, in pill form.”

References:

1. Morphic. Morphic to Present Positive EMERALD-1 Phase 2a Data for MORF-057 in Patients with Moderate to Severe Ulcerative Colitis in Abstract for UEGW 2023. Press Release. September 22, 2023. Accessed September 25, 2023. https://investor.morphictx.com/news-releases/news-release-details/morphic-present-positive-emerald-1-phase-2a-data-morf-057
2. Morphic. Morphic Reports Positive Topline Results of the EMERALD-1 UC Main Cohort; Orally Administered MORF-057 Achieves Primary Endpoint and Demonstrates Clinically Meaningful Improvements Across Secondary and Exploratory Measures. Press Release. April 25, 2023. Accessed September 25, 2023. https://investor.morphictx.com/news-releases/news-release-details/morphic-reports-positive-topline-results-emerald-1-uc-main
3. Clinicaltrials.gov. A Phase 2a Open-Label Study to Evaluate the Efficacy and Safety of MORF-057 in Adults With UC. August 4, 2023. Accessed September 25, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05291689