CHESTERBROOK, PA — Trevena, Inc. (Nasdaq: TRVN) announced data from 30 patients enrolled in the proof-of-concept study of TRV027, the Company’s novel AT1 receptor selective agonist, in hospitalized COVID-19 patients. The results showed that TRV027 was well-tolerated and provided initial evidence of its potential to improve biomarker and clinical endpoints associated with COVID-19 disease severity and progression. The study was led and funded by Imperial College London, with additional support through the British Heart Foundation Imperial Centre for Research Excellence Award.
“I am pleased to announce the results from this analysis, which provide initial evidence of the therapeutic potential of TRV027 to improve COVID-19 patient outcomes. With the ACTIV and REMAP-CAP COVID-19 platform trials currently evaluating TRV027, and data expected as early as mid-2022, we look forward to building upon these promising results,” said Carrie Bourdow, President and CEO of Trevena. “I would like to thank the patients and their families who participated, as well as Imperial College London for their partnership and interest in investigating our novel molecule.”
The primary endpoint was mean change from baseline D-dimer levels at three days. D-dimer is a biomarker used to monitor the risk of abnormal clotting throughout the vascular system. In patients with COVID-19, elevations in circulating D-dimer are also known to be an accurate predictor of critical disease progression and death. Among TRV027 treated patients, 70% (7 of 10) experienced a reduction in circulating D-dimer, compared to 27% (3 of 11) of patients on placebo. TRV027 was associated with a 92% probability of a potential beneficial treatment effect, based on a Bayesian model analysis recommended by the study’s Data Monitoring and Safety Committee (DMSC).
Notably, a post-hoc analysis indicated that patients receiving TRV027 experienced a 12 day reduction in average length of hospital stay compared to placebo (11.4 vs. 23.3 days), with a median reduction of 4 days (8 vs. 12).
“The overall outcomes from this analysis showing a reduction of D-dimer and a reduced length of hospital stay suggest that TRV027 may effectively combat dysregulation of the renin angiotensin system caused by a COVID-19 infection and thereby improve clinical outcomes,” said David Owen, M.D., Ph.D., Faculty of Medicine, Imperial College London and Head of Clinical Studies, NIHR Imperial Clinical Research Facility. “I am pleased that our efforts yielded these exciting findings, and I look forward to continue investigating this novel compound in two global multi-site platform trials.”
In March 2021, the study’s DMSC reviewed this data and unanimously found no safety or efficacy concerns, and it supported advancing TRV027 to a larger, more extensive study with clinical efficacy outcomes. As a result, the DMSC recommended closing enrollment at the interim analysis (~30 patients) prior to reaching the full study population number necessary to detect statistically significant treatment differences. The DMSC also recommended use of a Bayesian analysis on the primary endpoint to take full advantage of the accumulated data.
TRV027 is now being evaluated in two larger efficacy studies: ACTIV-4 Host Tissue led by Vanderbilt University Medical Center / NIH in the U.S. (ClinicalTrials.gov Identifier: NCT04924660), with data expected as early as mid-2022, and REMAP-CAP in the U.K. These two global, multi-site, multi-arm COVID-19 platform trials are expected to generate extensive scientific data in up to 600 patients on the potential clinical impact of TRV027 to prevent critical illness progression, multiorgan failure, and mortality in hospitalized patients with COVID-19 infection.
This was a randomized, double-blind, placebo-controlled proof-of-concept study that enrolled 30 hospitalized, non-ventilated patients aged 18 or older with a confirmed COVID-19 infection. 21 patients (n=10 for TRV027, n=11 for placebo) received at least 3 days of their assigned infusion and were evaluable for primary analysis. The primary objective of the study was to determine whether the coagulopathy associated with COVID-19 infection was driven by overactivation of the renin angiotensin system (RAS). The secondary objective was to determine whether dysregulation of other organ systems associated with COVID-19 infection is driven by overactivation of the RAS.
Among 28 patients who received treatment, 10 experienced at least one adverse event (AE) (n=5 for TRV027, n=5 for placebo), and 7 experienced at least one serious AE (SAE) (n=4 for TRV027, n=3 for placebo). All SAEs, including 3 deaths (n=2 for TRV027, n=1 for placebo), were assessed by the study clinician to be unrelated to study drug assignment or study procedures. At the 30 day follow-up, 24 patients survived (n = 12 for TRV027, n=12 for placebo).
Imperial College London sponsored and funded the study, with additional support through the British Heart Foundation Imperial Centre for Research Excellence Award and the NIHR Imperial Clinical Research Facility. The Company provided TRV027 in support of the study.
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