Kintor Pharmaceutical Ltd. said its androgen receptor (AR) antagonist, proxalutamide, reduced mortality risk by 92% and shortened median hospital length stay by nine days vs. standard of care, based on a preliminary analysis of phase III data from 590 hospitalized COVID-19 patients in Brazil. The company expects to have final data ready by the end of this month or early April, Chief Financial Officer Lucy Lu told BioWorld. Following the positive results, Kintor will start another trial in critically ill patients in intensive care, she said.

“The pandemic is very severe in Brazil, especially the new P.1 variant is very contagious and fatality rate is very high,” said Lu, who added that most of the patients enrolled in this study were infected by the new P.1 variant.

There have been two investigational-initiated trials in Brazil for proxalutamide. The first one enrolled outpatients to see how effective proxalutamide in reducing the hospitalization rate. The second one involved hospitalized patients.

“Currently, an open-label trial in ICU patients is under review by the Institutional Review Board of Brazil. That’s the third investigator-initiated study to be conducted in Brazil,” she said, adding that consent has been given for compassionate use of proxalutamide on ICU patients in Brazil.

An AR antagonist, proxalutamide can limit the expression of ACE2 and TMPRSS2, which plays a critical role in enabling SARS-CoV-2 to bind to and enter host cells in the lung.

Fewer deaths and shorter stay

The data Kintor released on March 11 were from an investigator-initiated phase III study. After the nod to start the study in January, the multicenter, randomized, double-blinded, placebo-controlled parallel assignment study began enrolling hospitalized men and women 18 years and older. Patients received either oral proxalutamide 300 mg or placebo once daily for 14 days.

The preliminary analysis was conducted on March 9 based on 294 patients (56.8% male) in the proxalutamide arm and 296 patients (57.8% male) in the control arm.

At day 14, mortality rate in the proxalutamide arm was 3.7% vs. 47.6% in the control arm, demonstrating a reduced mortality risk of 92%. In addition, 89.1% of the patients using proxalutamide were discharged from the hospital, whereas only 32.8% of the patients could be discharged in the control arm.

Patients in the proxalutamide arm also had shorter hospital stays, with a median of five days stay vs. 14 days in control arm.

When applying the WHO’s COVID-19 ordinal scale for measuring illness severity over time, proxalutamide also reduced the score by about 4 points, from a baseline of 5.7 to 1.7 vs. just a reduction of 0.3 points from baseline in the control arm (p<0.0001). The ordinal scale goes from zero, representing no infection, to eight, meaning death.

100% reduction in hospitalization leads to FDA trial nod

In January, Kintor also unveiled data from another trial evaluating proxalutamide in outpatients. Final data from that study, on male patients, showing proxalutamide could slow COVID-19 progression from mild to severe, helped Kintor get an IND approval from the FDA on March 5.

The randomized, double-blind and placebo-controlled clinical trial enrolled 319 patients in Brazil. The primary endpoints included the hospitalization rate, percentage of ICU usage, mechanical ventilation usage, death within 30 days, and the evaluation of clinical symptoms.

None of the 134 men enrolled in the proxalutamide arm needed to be hospitalized during the study vs. 27.3% of those in the control arm. Among women enrolled in the study, the results were similar, with only 1.7% of patients in the proxalutamide arm needing hospitalization vs. to 17.1% in the control arm.

Based on those data, the company has obtained FDA's consent to  proceed with a phase III trial of proxalutamide for the treatment of male COVID-19 patients with mild or moderate symptoms. 

The total size of that study is expected to be between 650 and 700 patients, enrolled in the U.S. and a few other countries, Lu said. 

With a similar patient group in its sights, Eli Lilly and Co. reported a 70% reduction in risk of COVID-19 hospitalizations and death with treatment of neutralizing antibodies bamlanivimab (LY-CoV555) and etesevimab (LY-CoV016). Etesevimab was licensed from Chinese drugmaker Shanghai Junshi Biosciences Co. Ltd.