The benefits of ensitrelvir use in patients with symptoms of long Covid and as a second-line treatment option for those hospitalised with Covid-19, have been presented at the recent European Scientific Working Group on Influenza and other Acute Respiratory Viruses’ (ESWI) Influenza Conference.
Ensitrelvir is an oral antiviral drug for Covid-19 manufactured by Shionogi, which is currently approved under the emergency regulatory approval system in Japan. The drug inhibits 3CL protease, an enzyme that is essential for the replication of the virus.
The first study presented at the ESWI Influenza Conference was an exploratory analysis of the Phase 3 part of the pivotal SCORPIO-SR trial. Conducted in Japan, South Korea and Vietnam, the researchers found that ensitrelvir may reduce the risk of a number of persistent and new late-onset symptoms associated with long Covid over one year.
Long Covid was analysed based on a patient-reported questionnaire at three, six and 12 months from the first date of treatment. The researchers defined long Covid by patient reports of ‘not having returned to pre-Covid health’ and having at least one (mild or more severe) symptom out of 27 possible symptoms.
The use of ensitrelvir at doses of 125 mg and 250 mg, showed a numerical relative risk reduction of 25% and 26% respectively when compared to the placebo for 27 long Covid symptoms at one year. A similar trend in risk reduction was observed at three and six months.
Furthermore, in subgroup analyses, there was a greater risk reduction in patients with a body mass index of ≥25 kg/m2 as well as in those with a median or higher symptom score at the start of treatment.
These results suggest that early treatment of Covid-19 with ensitrelvir could reduce the risk of a number of persistent and new late-onset symptoms associated with long Covid.
Dr Andreas Karas, vice president, medical affairs, Shionogi Europe, said: ‘As Covid-19 remains endemic, persisting symptoms continue to adversely affect millions of people worldwide. We’re pursuing further research to substantiate the potential of ensitrelvir as a treatment option for acute Covid-19 infection and whether this can prevent the long-term effects the virus can cause.
‘We look forward to sharing the results at ESWI and to hearing from the community as we advance our global ensitrelvir clinical development program.‘
Ensitrelvir for hospitalised patients
In the second study presented at the ESWI Influenza Conference, researchers suggested that for hospitalised patients with Covid-19 and significant co-morbidities who failed to respond to remdesivir as the first-line treatment, ensitrelvir could serve as an alternative treatment.
The small, real-world study from Japan, conducted at the Rinku General Medical Centre, included 21 high-risk hospitalised patients with Covid-19 infections who failed to respond to a three-day course of remdesivir.
These patients, who had either a mild or moderate severity infection and of whom a third (33.3%) had co-morbidities, then received five days of treatment with ensitrelvir 125 mg.
After five days of treatment, all 21 patients showed clinical improvement. Furthermore, no deaths or drug-related adverse events were observed at day 28, but one person later died in the hospital at day 59.
Masaya Yamato, an investigator on these trials and director of the Infectious Diseases Center at Rinku General Medical Center in Osaka, Japan, said: ‘While certain treatments are available for high-risk people with Covid-19 to reduce the risk of becoming seriously ill, additional treatment options are needed. These results indicate the potential for ensitrelvir to help address these needs.‘
Ensitrelvir remains an investigational drug outside of Japan. In April 2023, the FDA in the US recently granted fast track designation to the drug for Covid-19. This process is designed to facilitate the development and expedite the review of potential new therapies that treat serious conditions and fulfil an unmet medical need.