While much of the fanfare around COVID-19 treatments has dissipated, Shionogi has continued to press on in hopes that its Japan-approved protease inhibitor ensitrelvir could compete on a global stage. But a clinical misfire unveiled Monday has likely put a damper on those plans, at least in the U.S.
In the global phase 3 trial SCORPIO-HR, once-daily ensitrelvir—which goes by the brand name Xocova in Japan and falls into the same class of drugs as Pfizer’s Paxlovid and Merck & Co.’s Lagevrio—failed to chart a statistically significant reduction in time to sustained resolution of 15 common COVID-19 symptoms, missing the study’s primary endpoint.
For the study, Shionogi defined sustained resolution as complete absence of COVID symptoms for at least two days. Patients in the trial received ensitrelvir or placebo within three days of symptom onset, Shionogi said in a release.
In November 2022, ensitrelvir won an emergency approval in Shionogi’s home country of Japan. Japan’s Ministry of Health, Labor and Welfare upgraded the emergency nod to a standard approval in March. Outside Japan, Xocova is also approved in Singapore.
Despite the misfire in SCORPIO-HR, Shionogi said that a pre-defined supportive analysis showed a “significant difference” in the time to resolution of six COVID symptoms for patients on ensitrelvir. Ensitrelvir also displayed a “potent” antiviral effect by helping slash baseline viral RNA levels, Shionogi said.
SCORPIO-HR enrolled a range of symptomatic, non-hospitalized COVID patients in North and South America, Europe, Africa and Asia. Most of the enrollees were vaccinated and roughly 30% had health conditions that put them at risk for severe disease, including obesity, diabetes and hypertension, Shionogi said. The study took place when the omicron variant of the virus was predominant.
Shionogi carried out SCORPIO-HR in collaboration with the National Institute of Allergy and Infectious Disease as part of the National Institutes of Health’s public-private partnership Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV). The company’s 3CL protease inhibitor was previously blessed with fast-track designation from the U.S. FDA in 2023.
“These topline results, while mixed, confirm an antiviral effect and add to the existing clinical data and real-world evidence that we have seen for ensitrelvir in Asia,” Simon Portsmouth, M.D., Shionogi’s head of clinical development, said in a statement. “We will continue working with regulatory bodies to explore routes to making ensitrelvir available.”
Xocova’s original nod in Japan leveraged data showing the drug helped curb five typical omicron-related COVID-19 symptoms (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness) 24 hours faster than placebo. The initial emergency green light triggered a supply pact with Japan for the purchase of 1 million courses of the medicine. Shionogi ultimately bumped up its purchase agreement by another 1 million courses in December 2022 for a total sales haul of 100 billion Japanese yen ($642 million).
Last February, Shionogi’s CEO Isao Teshirogi, Ph.D., told Reuters that Xocova could generate an estimated $2 billion in annual sales if approved in the U.S. For 2023, the CEO said he was hoping for the drug to secure sales of around $1 billion to $1.5 billion. Shionogi, which operates on the Japanese fiscal calendar, has yet to release its full-year results for the 2023 earnings period, which ended on March 31 of this year.
Still, COVID drugs and vaccines of all stripes have suffered precipitous revenue declines ever since the switch from a pandemic to endemic market. The dearth of demand has led to the destruction of certain doses acquired by governments at the height of the pandemic, too.
Over the weekend, Kyodo News reported that Japan is set to liquidate 77% of the oral COVID antivirals it purchased during the pandemic as they expire. The country’s reserve of oral COVID meds—which includes Shionogi’s Xocova, as well as Paxlovid and Lagevrio—is worth approximately 300 billion Japanese yen ($1.93 billion), the news outlet said.