Evelo Biosciences, Inc. (Nasdaq:EVLO), a clinical stage biotechnology company developing SINTAX medicines as a new modality of orally delivered treatments for inflammatory disease, today announced positive data from its Phase 2 study evaluating EDP1815 versus placebo for the treatment of mild and moderate psoriasis. A statistically significant reduction in the Psoriasis Area and Severity Index (PASI) score, as measured by the proportion of patients achieving at least 50% improvement in PASI from baseline at the week 16 timepoint, was observed in the study. EDP1815 is an investigational oral biologic currently in development for the treatment of a broad range of inflammatory diseases, including clinical programs in psoriasis, atopic dermatitis, and COVID-19.
“These clinical results represent a significant advancement for those who live with inflammatory disease. This is the first Phase 2 study to demonstrate that we can harness the small intestinal axis to make a clinical impact on patients with an oral product candidate with safety and tolerability data comparable to placebo,”
said Simba Gill, Chief Executive Officer of Evelo.
“Based on these data, we intend to advance EDP1815 towards registration studies in psoriasis. We look forward to discussing our proposed next steps with health and regulatory authorities. This milestone brings us one step closer to realizing our vision of transforming healthcare by developing broadly acting oral, safe, effective, and affordable medicines to address the unmet needs of hundreds of millions of patients who live with inflammatory diseases.”
In the Phase 2 study, the PASI scores were assessed by both mean changes from baseline and responder rates. The primary endpoint was the mean percentage change in PASI between treatment and placebo and was prespecified as a Bayesian analysis. The Bayesian approach provides an estimate of the probability that EDP1815 is superior to placebo. The 16-week primary endpoint gave probabilities that EDP1815 is superior to placebo ranging from 80% to 90% across the prespecified analyses and cohorts.
The responder endpoint reports the proportion of patients who had a meaningful clinical response, which is defined as PASI-50 or greater. 25% to 32% of patients across the three cohorts who were treated with EDP1815 achieved a PASI-50 at week 16 compared to 12% on placebo. In cohorts 1 and 2 this difference in response rate was statistically significant (p <0.05). Cohort 3 was directionally similar (25% vs. 12%). The pooled PASI-50 response across all three EDP1815 cohorts, an exploratory analysis, was 29% vs. 12% for placebo and was also statistically significant with a p-value of 0.027. An increase in the number of capsules of EDP1815 did not lead to a dose response.
Additionally, several patients on EDP1815 achieved a PASI-75 or better, which was sustained or improved post treatment. For individuals who had a PASI-50 response or better, consistent effects in secondary and exploratory endpoints, including improvements in patient reported outcomes such as Dermatology Life Quality Index (DLQI) and Psoriasis Symptom Inventory (PSI), were observed.
EDP1815 was observed to be well tolerated in the Phase 2 study. The safety data were comparable to placebo and consistent with what was previously reported in a Phase 1b study. Adverse events (AEs) classified as “gastrointestinal” were comparable between active and placebo groups, with no meaningful differences in rates of diarrhea, abdominal pain, nausea, or vomiting. There were no related serious adverse events.
“I am very encouraged to see this Phase 2 data of EDP1815 in psoriasis,”
said Benjamin Ehst, M.D., Ph.D., Board-certified Dermatologist, Investigator and Clinical Associate Professor with the Oregon Medical Research Center, and Chief Investigator of EDP1815-201.
“It advances our scientific understanding of how to treat systemic inflammatory diseases and offers the prospect of a truly novel modality of treatment for patients with psoriasis. A drug with the combination of efficacy and safety results as observed here will likely be well received by dermatologists and their patients with mild and moderate disease, who are often faced with limited treatment options.”
EDP1815-201 is a double-blind, placebo-controlled, dose-ranging Phase 2 study designed to evaluate three doses of an enteric capsule formulation of EDP1815 versus placebo in 249 patients with mild and moderate psoriasis over a 16-week treatment period. In the study, the PASI scores were assessed by both mean changes from baseline and responder rates. The primary endpoint is mean percentage reduction in PASI score at 16 weeks. Secondary endpoints include the proportion of study participants who achieve a PASI-50 response or greater and other clinical measures of disease such as Physicians Global Assessment (PGA), Body Surface Area (BSA), PGA x BSA, PSI, and DLQI. Today’s results report out on the initial treatment phase of the study, which is now complete, and includes the 16-week treatment period with a 4-week follow-up. A six-month follow-up phase of the study is ongoing.