Candidate: TRV027
Type: AT1 receptor selective agonist with the potential to treat acute lung damage / abnormal blood clotting associated with COVID-19.
TRV027 is designed to combat disruption within the renin-angiotensin-aldosterone system (RAAS) by specifically binding to and rebalancing AT1 receptor activation, blocking the damaging pathway that leads to acute lung damage and abnormal blood clotting, while activating the cellular pathway that selectively targets reparative actions that improve lung function and promote anti-inflammatory effects.
2021 Status: Proof of Concept Results—Trevena on September 30 announced positive data from 30 patients enrolled in its proof of concept study of TRV027 in hospitalized COVID-19 patients. In the primary endpoint of mean change from baseline D-dimer levels at 3 days, 7 of 10 TRV027 treated patients (70%) experienced a reduction in circulating D-dimer, compared to 3 of 11 patients (27%) on placebo.
A post-hoc analysis showed 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). TRV027 was also 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).
The study was led and funded by Imperial College London, with additional support through the British Heart Foundation Imperial Centre for Research Excellence Award.
As of September 30, TRV027 was being evaluated in two larger efficacy studies: ACTIV-4 Host Tissue led by Vanderbilt University Medical Center and the NIH in the U.S. (NCT04924660), with data expected as early as mid-2022; and REMAP-CAP (NCT02735707) in the U.K. Both trials are expected to generate data from 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, Trevena said.
First Patient Dosed in ACTIV-4—Trevena said July 26 that the first COVID-19 patient had been enrolled in the NIH-funded ACTIV-4 Host Tissue (Accelerating COVID-19 Therapeutic Interventions and Vaccines) trial. The trial is designed to test four investigational agents that combat dysregulation of the renin-angiotensin-aldosterone system (RAAS) and the immune system caused by a COVID-19 infection.
ACTIV-4 Host Tissue is enrolling approximately 1,600 patients at over 50 sites in the U.S. The study is evaluating the impact of each intervention on recovery, supplemental oxygen use, need for mechanical ventilation, organ failure, and mortality. The trial is a multi-site, randomized, placebo-controlled, clinical trial with multiple treatment arms, each enrolling approximately 300-400 COVID-19 patients ≥ 18 years old. Four trial arms are testing investigational agents, including TRV027, that target the RAAS or the immune system through distinct mechanisms of action.
Selected for ACTIV-4d Trial—Trevena said May 6 that TRV027 had been been selected for the NIH’s ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) 4d RAAS trial. ACTIV-4d RAAS is designed to evaluate treatments targeting the RAAS and to determine whether modulation of the RAAS is an effective strategy for preventing progression to critical illness, multiorgan failure, or mortality in hospitalized COVID-19 patients.
ACTIV-4d RAAS is expected to enroll approximately 1,600 patients at more than 50 sites, including members of the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network, supported by the NIH’s National Heart, Lung, and Blood Institute. In addition to TRV027, ACTIV-4d RAAS is also expected to evaluate Constant Therapeutics’ TXA127, and Apeiron Biologics’ APN01.
NHLBI has awarded Vanderbilt Institute for Clinical and Translational Research (VICTR) a $60 million grant to lead the trial.
On April 21, Trevena said TRV027 had been selected for an international, multi-site, adaptive, Phase II/III study in COVID-19 patients being conducted by REMAP-CAP (Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia), a global network of clinicians, institutions, and research facilities. The REMAP-CAP COVID-19 ACE2 RAS Modulation Domain trial is designed to evaluate treatments targeting the renin-angiotensin system (RAS) and determine whether modulation of the RAS is an effective strategy for preventing multiorgan failure and mortality in hospitalized COVID-19 patients.
REMAP-CAP aims to evaluate treatments with the potential to reduce mortality, ICU use, and morbidity in severely ill patients with COVID-19. REMAP-CAP is financially supported by governments and research organizations worldwide.
TRV027 is being investigated in a proof-of-concept study by Imperial College London. A recent review of the interim data by the study’s Data Monitoring and Safety Committee (DMSC) found that there were no safety concerns with TRV027, and the DMSC supported advancing TRV027 to a larger, more extensive study with clinical efficacy outcomes.
2020 Status: Trevena said August 24 that Imperial College London (ICL) has launched a proof-of-concept study for TRV027 in COVID-19 patients. Through an ongoing collaboration with ICL, the company is evaluating the potential of TRV027 to treat acute lung damage / abnormal blood clotting associated with COVID-19. ICL is sponsoring and funding the study, with additional support through the British Heart Foundation Centre for Research Excellence Award.
The randomized, double-blind, placebo-controlled study will enroll approximately 60 hospitalized, non-ventilated patients aged 18 or older with a confirmed COVID-19 infection. The study’s primary objective is to assess whether TRV027 reduces abnormal clotting associated with COVID-19. The study will also evaluate the effect of TRV027 on lung function and other clinical outcomes. The company currently expects to report top-line data in the first quarter of 2021.
In April 2020, Trevena filed a provisional patent application with the U.S. Patent and Trademark Office covering the use of TRV027 to treat ARDS in COVID-19 patients.
COVID-19: 300 Candidates and Counting
To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types:
● ANTIVIRAL
● VAX
● ANTIBODY
● RNA
