Anticancer Drug Is Expected to Become The First Domestic Oral Drug For covid-19, What Exactly Is Proclamide?

On April 6, Kintor Pharma announced the key data results of the Phase III global multi-center clinical trial (NCT04870606) of proclutamide in the treatment of mild and moderate non-hospitalized patients with COVID-19. The hospitalization rate and mortality rate of patients are expected to become the first domestically produced oral drug for the COVID-19.

Anticancer drug counterattack becomes new crown oral drug,

What is the sacred place of Prokluamide?

Proxalutamide (Proxalutamide) is a novel androgen receptor (AR) antagonist, which is a novel compound derived from the optimization of the anti-prostate cancer drug enzalutamide. Phase II clinical trials have been completed, with Phase II clinical trials (NCT03899467) for the treatment of metastatic castration-resistant prostate cancer (mCRPC), and Phase II clinical trials for the neoadjuvant treatment of high-risk prostate cancer with proclutamide combined with androgen deprivation therapy (ADT) Trial (NCT05076851) is recruiting.

In the field of cancer treatment, AR is a relatively mature target, so how are anticancer drugs related to new coronary pneumonia? On March 5, 2020, researchers such as Stefan Phlmann and Markus Hoffmann of the University of Göttingen in Germany found that when the new coronavirus (SARS-CoV-2) invades the human body, the spike protein of the virus interacts with angiotensin-converting enzyme on the surface of human cell membranes. 2 receptor protein binding (ACE2), while the transmembrane serine protease (TMPRSS2) in human cells is responsible for initiating the spike protein, initiating the fusion of the viral outer membrane and the cell membrane, and facilitating the entry of the virus into cells.

Previous studies related to prostate cancer have shown that androgens combined with AR can promote the expression of TMPRSS2 and ACE2 in prostate cells. In June 2020, American hair expert Andy Goren found that androgenetic alopecia is related to the pathogenesis of the new crown. Coupled with the clinical phenomenon that the majority of patients with new crowns are male and the disease is more severe, Pioneer Pharmaceuticals has taken a different approach and used the anti-prostate cancer drug Prolukamide for the treatment of patients with mild COVID-19.

It is expected to become the first domestically produced new crown oral drug,

What are the advantages of Prokluamide?

The announced Phase 3 clinical trial is a randomized, double-blind, placebo-controlled, multicenter registrational trial in non-hospitalized patients 18 years of age and older who developed mild or moderate COVID-19 within 5 days. -19-related symptoms, at least three days before administration, confirmed by laboratory methods such as PCR as a patient with new coronavirus infection, regardless of gender. The exclusion criteria were blood oxygen saturation (SpO2) ≤ 93% or oxygenation index < 300, respiratory rate ≥ 30 beats per minute, heart rate ≥ 125, glomerular filtration rate < 30 ml/min, etc. Other exclusion indicators included Patients with severe heart disease, allergies, hemodynamic instability, suspected other microbial infections (eg HIV), surgery within 7 days, or other serious medical conditions. As you can see, the entry criteria for this study are very strict.

The study endpoints of the trial included the percentage of subjects who did not experience hospitalization for ≥24 hours or oxygen intake for ≥24 hours due to SpO2≤93% or death by day 28; subjects were hospitalized or inhaled due to SpO2≤93% within 28 days Oxygen ≥ 24 hours or incidence of death; change in viral load from baseline to day 28 and safety assessment, etc.

The results of this phase III clinical trial showed that proclutamide can effectively reduce hospitalization/mortality, and the corresponding protection rate of subjects who took the drug for more than 7 days was 100%. In subjects with high risk factors (such as obesity, diabetes, hypertension, etc.) in the middle-to-old age group, hospitalization and mortality were significantly reduced. Prokalutamide can significantly and continuously reduce the new coronavirus load, and can improve some of the related symptoms of new coronary pneumonia such as fever, shortness of breath, and cough better than the placebo control group.

In terms of safety, the overall tolerance of proclutamide in the treatment of patients with mild to moderate new crown disease is good, and it is safe and controllable. During the entire trial, the incidence of adverse events was 7.9% in the control group vs 9.6% in the prokalutamide group, most of which were mild, and the most common adverse event was dizziness (1.1% in both the control and prokalutamide groups). %), and the incidence of any other adverse event was <1%. No serious adverse events occurred during the study.

The world's first approved oral drug for the treatment of COVID-19 is Molnupiravir, developed by Merck and Ridgeback Biotherapeutics, which is a nucleoside analog that targets RNA polymerase. The enrolled patients were also patients with mild to moderate new crowns, and the interim results showed that Molnupiravir, taken five days after the onset of symptoms, reduced the probability of hospitalization or death by 50% in mild and moderate adult patients.

Paxlovid, which has entered the domestic medical insurance, is a combination of PF-07321332 and ritonavir. The target of PF-07321332 is SARS-CoV-2-3CL protease, and ritonavir is a common HIV drug, which can competitively inhibit the metabolism or decomposition of PF-07321332 in vivo, prolonging the half-life of the former to improve the efficacy. In terms of efficacy, according to data released by Pfizer at the end of 2021, compared with placebo, Paxlovid, taken within three days of onset of symptoms, can reduce the probability of hospitalization or death in mild and moderate adult patients by 89%.

Compared with the two approved oral drugs for the treatment of COVID-19, Prokluamide has performed well.

However, at the end of 2021, Kintor Pharmaceutical disclosed the results of the interim analysis of the clinical trial, showing that "the clinical trial did not reach statistical significance due to the small number of events". Since then, the share price of Kintor Pharmaceutical has also been directly discounted. , and after the announcement of the final results on April 6, a shocking reversal was staged, and the effect of cardiac drugs was exceptionally significant. Another global multi-center Phase III clinical trial (NCT04869228) of Prokluamide in the treatment of COVID-19 is underway in Kintor Pharmaceuticals, and the indication is also for non-hospitalized COVID-19 patients with mild to moderate symptoms.

In the context of the launch of Merck and Pfizer's new crown special effect drugs, whether the domestic new drug Prokluamide can buck the trend and gain a place in the field of new crown treatment, let us wait and see.