The Company is actively reviewing current studies characterizing the outbreak of COVID-19. These published reports clearly illustrate that acute kidney injury and acute pulmonary injury are key factors in the most serious cases of COVID-19 hospitalization and death.
XORTX believes that XRx-101 (a formulation of Oxypurinol) could be relevant and important for decreasing kidney and lung injury, as well as health consequences associated with Coronavirus infection. Indeed, xanthine oxidase inhibitors (XOI) have been reported to have a potent antiviral effect against influenza-A virus5 and herpes infections suggesting a potential therapeutic benefit for suppressing the Coronavirus infection.
XRx-101 as a Treatment for Coronavirus / COVID-19
Oxypurinol (XORTX’s XRX-01) is a well studied drug that is known to be clinically safe and effective for inhibiting xanthine oxidase and decreasing production of uric acid. Owing to its advanced development status, Oxypurinol could be quickly developed to help treat those most severely affected by COVID-19. XORTX has filed new intellectual property rights for XRx-101 for the treatment of respiratory and kidney disease due to viral infection.
COVID-19 is a serious viral infection due to a coronavirus. Coronavirus infections such as SARS and MERS and specifically COVID-19 can be frequently accompanied by pneumonia, acute kidney injury, proteinuria and hematuria1,2. Acute kidney injury (“AKI”) has been identified as an independent risk factor for patients’ in-hospital mortality due to COVID-19 as well as other Coronavirus infections2. Early reports suggested a lower incidence (between 3% to 9%) of AKI in those with COVID-19 infection2,6,7. Recent reports, however, have shown a higher frequency of renal abnormalities. A study of 59 patients with COVID-19 found that 34% of patients developed massive albuminuria on the first day of admission and 63% developed proteinuria during their stay in hospital8.
Based on these recent studies, the Company believes that its Oxypurinol formulation, XRx-101, has the potential to be a front-line treatment for severe cases of Coronavirus and that this therapy has the ability to decrease morbidity and mortality in hospitalized patients. Management’s belief that XRx-101 is a possible treatment for COVID-19 is based upon its potential anti-viral properties, and historic animal and human data that show that acute tissue injury can lead to rapid accumulation of uric acid and uric acid crystals that aggregate in kidneys and induce acute kidney injury3,4. When acute kidney injury accompanies pneumonia, post-discharge outcomes are worse than either diagnosis alone. Patients who survive a pneumonia hospitalization and develop acute kidney injury are at high risk for major adverse kidney events including death and should receive careful follow-up4. Perhaps more importantly, Oxypurinol has been previously studied for anti-viral properties9, a characteristic that may decrease morbidity and mortality of COVID-19. Importantly, Oxypurinol has in the past received an “Approval Letter” from the US FDA, potentially accelerating development for this purpose.
The triple action of XRx-101, as an anti-viral therapy, to decrease the production of uric acid and increase the aqueous solubility of uric acid thereby decreasing uric acid crystal formation associated with tumor lysis “like” syndrome due to Coronavirus infection. Decreasing uric acid with a xanthine oxidase inhibitor is associated with decreased inflammation, oxygen radical concentrations, cytokine concentration and tissue protection. Any agent that decreases the severity of primary or secondary pneumonia leading to acute kidney injury is potentially highly relevant.
The Virus
The complete clinical picture with regard to COVID-19 is not fully known, but evolving rapidly as more is learned. Reported illnesses have ranged from very mild (including some with no reported symptoms) to severe, including illness resulting in death. While information so far suggests that most COVID-19 illness is mild, recent reports suggest serious illness occurs in 10-14% of cases. Older people and people of all ages with severe chronic medical conditions — like heart disease, lung disease and diabetes, for example seem to be at higher risk of developing serious COVID-19 illness. A CDC Morbidity & Mortality Weekly Report that looked at severity of disease among COVID-19 cases in the United States by age group found that 80% of deaths were among adults 65 years and older with the highest percentage of severe outcomes occurring in people 85 years and older.
References
- Saraladevi Naicker, Chih-Wei Yang, Shang-Jyh Hwang, Bi-Cheng Liu, Jiang-Hua Chen, Vivekanand Jha, The Novel Coronavirus 2019 Epidemics and Kidneys, Kidney International March 2, 2020. https://www.kidney-international.org/article/S0085-2538(20)30251-9/pdf
- Cheng, Y, Luo R., Wang K., Zhang M., Wang Z., Dong L., Li J., Yao Y., Ge S., Xu g., Kidney Impairment is associated with in-hospital deal of Covid-19 patients, medRxiv, March 04_2020 https://www.medrxiv.org/content/10.1101/2020.02.18.20023242v1
- Wilson FP., Tumor Lysis Syndrome, Adv Chronic Kidney Dis, 21(1)18, 2014 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017246/
- Chawla LS., Amdur RL., Faselis C., Kimmel PL., Palant CE., Impact of Acute Kidney Injury in Patients Hospitalized with Pneumonia, Crit Care Med, 45(4)600-606, 2017 https://www.ncbi.nlm.nih.gov/pubmed/28291091
- Perez-Mazliah D et al, Allopurinol reduced antigen-specific and polyclonal activation of human T-cells, Frontiers in Immunology, Sept 2012
- Wang D, Hu B, Hu C, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA,2020,doi:10.1001/jama.2020.1585.
- Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of 2019 novel coronavirus infection in China. medRxiv preprint first posted online Feb. 9, 2020. https://doi.org/10.1101/2020.02.06.20020974Li Z,
- Wu M, Guo J, et al. Caution on Kidney Dysfunctions of 2019-nCoV Patients. medRxiv preprint doi: https://doi.org/10.1101/2020.02.08.20021212.
- El-Farrash, Youssef JM., and El-Mongy SE., Allopurinol as a potential therapeutic agent for recurrent herpes labialis, J Med Dent Sci, Jun 50(2):147-154