Concerns Remain as Kintor Pharma’s Proxalutamide Shows Unbelievably High Efficacy Against Covid-19 Infections in Phase 3 Trials

Kintor Pharmaceutical Limited (Kintor Pharma) has indicated the higher recovery rate and lower all-cause mortality of proxalutamide, its Covid-19 candidate drug, on Covid-19 patients without mechanical ventilation in a randomized, double-blind, placebo-controlled, and parallel-design clinical trial in Brazil. Besides, Kintor Pharma will release the interim data of proxalutamide from a multi-regional Phase 3 clinical trial in countries including the US to treat Covid-19 outpatients this month (December).

Founded in 2009, Kintor Pharma focuses on developing drugs for androgen-receptor (AR)-related diseases with significant unmet medical needs, including prostate cancer, breast cancer, liver cancer, Covid-19, and other conditions that lack effective treatments. 

The Suzhou-based company has numerous drug candidates in the clinical-stage, including proxalutamide, its second-generation androgen receptor antagonist, to treat prostate cancer, metastatic breast cancer, and Covid-19.

Related Article: Updated Trial Data Shows Lower Efficacy for Merck’s Oral COVID-19 Pill

Efficacy of Proxalutamide against Covid-19

Proxalutamide is a nonsteroid, selective high-affinity antagonist of AR developed in-house and previously used to treat prostate and breast cancer. Kintor Pharma started research on the efficacy of proxalutamide against Covid-19 after they observed a higher incidence of severe cases among adult males than that among adult females. 

 “The clinical phenomenon indicated that the coronavirus might be correlated with human’s androgen level. Therefore, proxalutamide as an AR antagonist might be an effective therapy to treat infections,” the Chief Financial Officer Lucy Lu said to the Global Times.

Besides, androgen-dependent expression of TMPRSS2, which facilitates membrane fusion and entry of SARS-CoV-2 in nonprostatic tissues (especially the lung), might be crucial to men’s increased susceptibility to Covid-19 severity and mortality.

 “According to our in-house research and with reputable professors in the US, proxalutamide could significantly inhibit the entry of the coronavirus into host cells by transcriptionally down-regulating the expression of TMRPSS2 and ACE2, which make it not only effective against the wide-type coronavirus but numerous following mutations like Alpha, Delta, and Gamma,” Lu added.

Proxalutamide has shown its good efficacy in Brazil, with a 128% higher recovery rate and reduced mortality rate by 77% (over 28 days) compared to those treated with placebo. Moreover, proxalutamide had proved a good safety profile in previous clinical trials of treating prostate cancer and would be better for Covid-19 patients with a shorter treatment cycle (only one to two weeks).

Doubts Remain

However, the unexpectedly high efficacy of proxalutamide raised doubts over the authenticity of the data, especially after the manuscript of the Brazil study was rejected by The New England Journal of Medicine and The Lancet. In response to the refusal by the two magazines and doubts over the transparency of the clinical trials in Brazil, Lu explained that the magazine editors thought the data was too good and they had to check the original data. In contrast, they did not have the capacity to do so.

In addition to the doubts on the clinical trials, there are debates on whether androgen deprivation therapy (ADT) has a protective effect against SARS-CoV-2 infection. A systemic review and meta-analysis showed that ADT did not decrease the infection risk, hospitalization rate, ICU admission, and mortality risk of Covid-19 patients. Other studies also demonstrated that ADT could not reduce mortality in prostate cancer patients with SARS-CoV-2 infection. Further studies/trials and more data are needed to validate whether ADT may be an option for Covid-19 treatment.

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GeneOnline