Investigators hope ATR-002 drug will also be effective against ‘Long-Covid’
Tübingen, Germany-based Atriva Therapeutics, a biopharmaceutical company that is pioneering the development of host-targeting antiviral therapies, has enrolled its first patient in its Phase II RESPIRE  trial in COVID-19. Prof. Martin Witzenrath, M.D., Vice Director Department of Infectious Diseases and Respiratory Medicine, supervised the first administration of study medication (MEK inhibitor ATR-002 or placebo) at the Charité – Universitätsmedizin Berlin, Germany.
Dr Rainer Lichtenberger, CEO of Atriva Therapeutics, commented: “We are excited to assess the efficacy of ATR-002 in treating COVID-19 and are looking forward to the results of the clinical trial. We can now test our lead candidate against SARS-CoV-2 because our pharmacological target is a common cellular mechanism that RNA viruses use. ATR-002 leaves the virus itself untouched but blocks a cellular factor that the virus needs for its replication and has the potential to reduce the viral load in the infected host.
“Host-directed approaches maintain efficacy also against mutated viruses – a problem that we are commonly seeing in the influenza virus and, unfortunately, in SARS-CoV-2 as well. If we were to see the positive outcomes of the trial we hope for, ATR-002 could provide efficient help against COVID-19 regardless of the given genetic subtype of the underlying viral strain.”
Prof. Gernot Rohde, M.D., Head of Pneumology and Professor for Respiratory Medicine and Allergology at the Goethe University Hospital, Frankfurt am Main, Germany and Global Coordinating Investigator of the RESPIRE trial, said: “While we have been lucky that SARS-CoV-2 vaccines were developed at unprecedented speed, we still are in desperate need for effective therapies against COVID-19. The pandemic situation remains very critical and is far from being under control.
“Being able to contribute to the development of a COVID-19 therapy, I am very much looking forward to the effects that we may see with ATR-002. I am convinced that a medication that can prevent hospitalized patients with a moderate to severe stage of COVID-19 from deteriorating and requiring ICU admission and ventilator support would mean huge progress and could also play a role in impeding the severe long-term effects that are being described as “Long COVID” Syndrome (PASC).”
RESPIRE is a randomized, double-blind, placebo-controlled, international, multi-center Phase II clinical trial in 220 adult patients with moderate to severe COVID-19, requiring hospitalization, but not requiring ICU admission or ventilator support at the time of screening or randomization. On top of standard of care, half of the patients will receive ATR-002 900 mg, administered as tablets once daily on day 1, followed by ATR-002 600 mg once daily on days 2 to 6. Patients in the control group will receive placebo in a matching scheme, on top of standard of care.
The primary objective of the study is to demonstrate the efficacy of ATR-002 versus placebo in addition to standard of care; secondary endpoints include the measurement of changes in clinical signs and symptoms as well as other relevant clinical parameters. Outcomes will be assessed based on the clinical severity status on day 15, using a 7-point ordinal scale as suggested by the WHO COVID-19 Therapeutic Trial Synopsis . All patients will be followed-up for 90 days. The study will also evaluate the pharmacokinetics of ATR-002.
ATR-002’s mode of action
Atriva’s lead product ATR-002 is developed specifically to treat diseases such as influenza and COVID-19, caused by RNA viruses. ATR-002 is a clinical stage MEK inhibitor drug candidate targeting the intracellular Raf/MEK/ERK signaling pathway. This pathway is central for replication of many RNA viruses, such as the influenza virus, hantavirus or respiratory syncytial virus (RSV) and also SARS-CoV-2, the virus that causes COVID-19.
In influenza virus infected cells, the interaction of ATR-002 with MEK (MAPK/ERK kinase) prevents export of the viral genome protein complexes (ribonucleoprotein, RNP) from the nucleus to the cytoplasm, thus blocking the formation of functional new viral particles. This ultimately reduces the viral load in the body. In addition, ATR-002 has the potential to modulate the pro-inflammatory cytokine response of the body, avoiding overshooting cytokine response that can be caused by such viral infections. MEK inhibition can reduce the gene expression of some of the cytokines involved, like TNF-α, IL-1ß, IP-10, IL-8, MCP-1 and MIP-1a, and thus mitigate the overactive inflammatory response in the lungs of patients who are severely ill with influenza or COVID-19.