Disappointing Results End 9 Meters' Phase III Trial for Celiac Treatment

North Carolina-based 9 Meters Biopharma, a clinical-stage company that creates treatments for digestive diseases, is discontinuing its Phase III trial studying larazotide for the treatment of celiac disease due to disappointing interim results. 

Larazotide is a synthetic eight-amino acid peptide tight junction regulator that inhibits paracellular permeability. It is being studied as a treatment for celiac disease, a genetic condition that affects about 2 million people in the United States.

The CedLara trial is a Phase III clinical trial for patients with celiac disease who continue to experience gastrointestinal symptoms while adhering to a gluten-free diet. The 24-week study includes 525 patients who were equally distributed across three arms of the trial, one of which received a 0.25mg dose of larazotide, one that received 0.5mg of larazotide and one that received a placebo. The primary endpoint of the study is the mean change from baseline for celiac symptom severity based on the CeD PRO (celiac disease patient-reported outcomes) abdominal domain score over 12 weeks.

However, after a 12-week double-blind treatment phase and an additional 12-week continued safety phase, the results did not show that larazotide was effective. 9 Meters Biopharma had an independent statistician analyze the interim results to re-estimate the treatment group size required to detect a statistically significant clinical effect.

Based on the statistician’s analysis, the additional number of patients needed to determine a significant clinical outcome between placebo and larazotide would be too large to feasibly continue the trial.

The results were surprising, as larazotide had shown positive results in a previous Phase II clinical trial. The previous study included 342 adult patients with celiac disease who had been on a gluten-free diet for at least 12 months. In those patients, a 0.5 mg treatment of larazotide significantly reduced symptoms of celiac disease.

Larazotide has also shown positive results for other gastrointestinal diseases. In February, 9 Meters Biopharma published data in the journal Critical Care Explorations on using larazotide to treat multisystem inflammatory syndrome resulting from COVID-19 in children. All four children who received larazotide experienced significantly faster resolution of gastrointestinal symptoms. Additionally, the children’s hospital stays were shorter on average compared to children who did not receive larazotide.

Despite the disappointing results of the Phase III CedLara trial, the company said it will conduct additional analyses of the data to determine if a subgroup of patients may have been responsive to treatment.

“We plan to continue to analyze the data over the coming weeks to determine if other individual or groups of celiac symptoms might benefit from treatment with larazotide. Completion of the analyses and engagement with FDA will determine further plans for larazotide for the treatment of celiac disease,” Patrick Griffin, M.D., FACP, chief medical officer of 9 Meters, said.

The company also said the setback with larazotide will not affect its other drug candidates. Resources from the CedLara trial will be redistributed throughout the company to focus on other areas, especially its drug vurolenatide.

"Despite this outcome, 9 Meters will continue its mission of developing novel therapeutics for rare or debilitating GI disorders, and we remain enthusiastic about the prospects for vurolenatide for short bowel syndrome and our early-stage pipeline. Pending the final analysis, financial and human resources previously dedicated to this study will be re-deployed to advance our development program for vurolenatide and our early-stage product candidates,” John Temperato, 9 Meters CEO and president, said in a statement.