The Role of the AT1 Receptor in COVID-19
In a COVID-19 infection, the SARS-coronavirus-2 binds to and degrades ACE2 proteins in the lungs, driving dysregulation of the renin-angiotensin-aldosterone system. This results in overactivation of the AT1 receptor, which . causes downstream acute lung injury that can progress to acute respiratory distress syndrome (ARDS), a major complication leading to mortality. COVID-19-related ARDS is associated with a mortality rate of 66% - 94%.1* Activation of the AT1 receptor is also known to contribute to the development of abnormal blood clots, which can lead to deadly complications such as pulmonary embolism or stroke. Approximately one-third of hospitalized COVID-19 patients develop clotting complications.2
About TRV027
Trevena is developing TRV027, a novel AT1 receptor selective agonist designed with Nobel Prize winning technology, as a potential treatment for acute respiratory distress syndrome (ARDS) and abnormal clotting for COVID-19 patients. The potential therapeutic benefit of TRV027 is two-fold: 1) TRV027 competitively binds to the AT1 receptor, which disrupts overactivation caused by the SARS-coronavirus-2 and rebalances hormonal activity within the RAAS. 2) The unique mechanism of action of TRV027 preferentially engages the signaling pathway that promotes downstream reparative effects on lung tissue, as well as reduces abnormal blood clotting associated with COVID-19.
TRV027 has been selected to be included in the National Institutes of Health ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) trial being led by the Vanderbilt University Medical Center, as well as REMAP-CAP, a globally recognized research network that is leading the search for cutting-edge COVID-19 therapies.
| Program | Molecular Target | Therapeutic Target | Current Phase | PC | PH1 | PH2 | PH3 | NDA | Approved |
|---|---|---|---|---|---|---|---|---|---|
| OLINVYK® (oliceridine) injection | Mu receptor | Acute pain | Approved | Intravenous PC complete | PH1 complete | PH2 complete | PH3 complete | NDA complete | Approved in progress |
| TRV045 | S1P receptor | Diabetic neuropathic pain | PH1 | Oral PC complete | PH1 in progress | PH2 not started | PH3 not started | NDA not started | Approved not started |
| TRV045 | S1P receptor | Epilepsy | PH1 | Oral PC complete | PH1 in progress | PH2 not started | PH3 not started | NDA not started | Approved not started |
| TRV250 | Delta receptor | Acute migraine | PH1 | Oral/Subcutaneous PC complete | PH1 in progress | PH2 not started | PH3 not started | NDA not started | Approved not started |
| TRV734 | Mu receptor | Opioid use disorder | PH1 | Oral PC complete | PH1 in progress | PH2 not started | PH3 not started | NDA not started | Approved not started |
TRV027 is an Investigational Product not approved by FDA for distribution in the US.
- Gibson PG et al, Med J Aust, 2020. *In patients requiring ventilation.
- Klok FA et al, Thromb Res, 2020.