The data demonstrated that the drug, when given to the patients for more than seven days, offered a protection rate of 100%.
Suzhou, China-based Kintor Pharmaceutical announced topline results from its Phase III MRCT trial of proxalutamide in outpatients with mild to moderate COVID-19. The study evaluated the patients regardless of vaccination status or risk factors.
The data demonstrated that the drug, when given to the patients for more than seven days, offered a protection rate of 100%. It reduced hospitalization or death in COVID-19 patients, notably in the middle-aged and elderly with high-risk factors.
Proxalutamide is an ACE2 and TMPRSS2 inhibitor. ACE2 is the primary receptor on human cells that allows the SARS-CoV-2 virus to latch on and enter the cell. The virus uses TMPRSS2 for S protein priming, which is to say, it activates the virus’s S protein. Inhibiting both of these protein receptors stalls the virus’s ability to enter and infect cells. And by promoting the clearance of the virus it decreases inflammation by activating the Nrf2 pathway, which prevents overproduction of IL-6, proinflammatory cytokines and chemokines.
“The topline data of this pivotal study demonstrates the clinical efficacy of proxalutamide in the mostly U.S. COVID-19 population with a significant reduction of hospitalization and death rate in patients,” stated Dr. Tong Youzhi, founder, chairman and chief executive officer of Kintor.
Youzhi went on to say, “It is important to note that proxalutamide has showed COVID-19 viral load reduction against both Delta and Omicron variants, which is important as new variants continue to arise. The continued increase in COVID-19 cases serves as a reminder that the world urgently needs effective and safe oral drugs with different mechanisms of action.”
The company plans to apply for emergency use authorization in the U.S., and the equivalent in China and other countries.
The clinical trial enrolled 733 participants with a positive COVID-19 test and symptoms onset regardless of vaccination status or other risk factors. Of them, 99% were recruited in the U.S. Participants received either 200mg of proxalutamide once-a-day plus standard of care (SOC) or placebo plus SOC for 14 consecutive days.
The endpoints included percentage of patients who were not hospitalized for any reason for at least 24 hours, or who did not require supplemental oxygen for at least 24 hours in response to SpO2 ≤93 and who were alive by Day 28; the percentage of patients with all-cause hospitalization requiring supplemental oxygen or all-cause death by Day 28; and changes of SARS-CoV-2 viral load from baseline to Day 28.
The drug was well tolerated with manageable side effects in the patient populations. Kintor found treatment-related adverse events were comparable to the control group, with the majority of treatment-emergent adverse events (TEAE) being mild. The most common side effect was dizziness. No serious adverse events were observed.
Of all patients in the trial who received at least one day of treatment, eight who received placebo were hospitalized, with one death, versus four patients hospitalized in the proxalutamide group with zero deaths. All hospitalizations were related to COVID-19. The drug decreased the risk of hospitalization or death by 50% compared to the control group.
In patients who received treatment with the drug for more than one day, seven patients in the placebo group were hospitalized including one death, compared to two patients who received proxalutamide, with, again, zero deaths. In this longer-treatment group, the drug reduced the risk of hospitalization or death by 71% compared to the control cohort.
And in patients who received treatment for more than seven days, six in the placebo cohort were hospitalized with one death compared to no hospitalization or death in the proxalutamide cohort. In this group, proxalutamide decreased the risk of hospitalization or death by 100% compared to the placebo cohort.
In terms of comorbidities and age, in patients 50 years or older who were obese, the drug reduced the risk of hospitalization or death by 100%. In patients 60 years or older with or without underlying medical conditions, proxalutamide also reduced the risk of hospitalization or death by 100%. And in patients 60 years or older who had at least one underlying medical condition, such as obesity, diabetes or hypertension, there were no hospitalizations or deaths in the group receiving the drug.
Proxalutamide would appear to be on track for authorization, to join Pfizer’s Paxlovid (nirmatrelvir; ritonavir) and Merck and Ridgeback Biotherapeutics’ Lagevrio (molnupiravir) as effective oral antiviral treatments for mild to moderate COVID-19.
