5 Existing Drugs That May Treat COVID-19
A review of the current clinical trials
Various drugs are being tested to treat COVID-19 in clinical trials around the world. So far the clinical trial results have been mixed but mainly negative. There were trials on two different drugs Remdesivir and Lopinavir which were the front runners as a COVID-19 treatment.
So far the Remdesivir trial has shown that patients using Remdesivir had a quicker recovery compared to the control group, but unfortunately, the survival benefits were not statistically significant.
Even though the results seemed mixed, the US and Japan have licensed Remdesivir as a COVID-19 treatment. [1] There are still approximately 26 pending Remdesivir trials so let’s see how they turn out.
In addition, the Lopinavir-ritonavir trial showed that there was no significant clinical benefit using Lopinavir-ritonavir, as the mortality rates and the viral RNA loads were similar to the control group. [2]
However, this does not mean there won’t be a positive result from any of the clinical trials! There are plenty of drugs that are or will be going through clinical trials for COVID-19.
Here’s a snippet of some of them:
1. Tocilizumab
Tocilizumab is an antibody-based drug that is commonly used to treat rheumatoid arthritis. Tocilizumab works by binding to the interleukin 6 receptor which prevents interleukin 6 binding to the receptor, and subsequently, this reduces inflammation.
This drug might be beneficial in the case of COVID-19 patients because of the “cytokine storm” that occurs, this means that a large number of proinflammatory cytokines such as interleukins 6 and 12 are released to amplify inflammation and this leads to severe consequences such as pneumonia. [3]
Furthermore, a clinical trial in China showed that Tocilizumab was effective in treating COVID-19 patients, as the coronavirus symptoms had decreased, and 90.5% of patients were discharged after 13.5 days of Tocilizumab treatment on average. [3]
These are positive results from an initial study but there are many more studies yet to be conducted! There are approximately 52 clinical trials on Tocilizumab that have started or will be starting soon worldwide. These clinical trials will provide heaps of data to give a fuller picture of Tocilizumab and will help researchers decide whether Tocilizumab is an effective treatment for COVID-19.
2. Ruxolitinib
Another candidate drug is Ruxolitinib, a Janus kinase (JAK) inhibitor that is used to treat graft-versus-host disease, polycythemia vera, and myelofibrosis, a type of blood/bone marrow cancer. Ruxolitinib inhibits dysfunctional JAK signaling which is a characteristic of myelofibrosis. [4]
There are currently 16 clinical trials for Ruxolitinib against COVID-19 listed. Many of these clinical trials have recently begun, and several of these will be commencing soon.
Researchers are hoping that Ruxolitinib can reduce the inflammation caused by Coronavirus, and subsequently prevent lung deterioration and multiple organ failure. Early results from these clinical trials will hopefully be available from mid-July onwards.
3. Duvelisib
A phase 2 clinical trial using Duvelisib, a drug used for chronic lymphocytic leukemia and small lymphocytic lymphoma has been estimated to start at the end of June. [5] This clinical trial is a collaboration between Verastem and Washington University School of Medicine.
Due to the previous in vitro results, researchers believe that Duvelisib, a phosphoinositide 3-kinase inhibitor, can suppress the hyperactivation of the immune system and thus may be able to diminish the impact of coronavirus and the severe complications that result because of it.
In the clinical trial, the patients will have 25 mg of Duvelisib twice a day for a period of ten days. The researchers are primarily interested in whether Duvelisib makes a significant change to the survival rate of COVID-19 patients.
This is the only clinical trial using Duvelisib at the moment and the primary study is estimated to be completed by 31st of July, 2021.
4. Canakinumab
Canakinumab is another antibody-based drug, Canakinumab specifically targets interleukin-1 beta. Canakinumab is used to treat cryopyrin-associated periodic syndromes and a few other rare auto-inflammatory disorders. [6]
At the moment there are three clinical trials that have recently started which are testing Canakinumab to treat COVID-19 and the pneumonia-related complications.
A case study was published in the BMJ journal, a 70-year-old lady had cryopyrin-associated periodic syndrome which she was taking Canakinumab for. The lady caught coronavirus from her friend and subsequently tested positive for coronavirus. Due to her age and medication, she seemed to be at high risk of complications. However, 12 days later she tested negative for coronavirus.
It has been hypothesized because she was using Canakinumab, this may have prevented the hyper inflammation associated with COVID-19 and may have kept her stable. This is a single case study that may provide insight into the benefits of Canakinumab. However, the clinical trials will provide the full-proof data about Canakinumab's abilities. [7]
In the three different clinical trials, patients will be infused with different dosages of Canakinumab. The dosages will be between 300 mg and 750 mg depending on the study. In the trials, the dosage will be determined by the participant’s body weight, and by the group allocation.
5. FT516
Lastly, there is a phase 1 clinical trial being conducted by the University of Minnesota using FT516 against COVID-19. FT516 is a Natural Killer (NK) cell-based immunotherapy developed from iPSCs. The NK cells have been engineered to have CD16 Fc receptors that increase their anti-viral activity so that antibody-mediated cell death can be promoted. [8]
The clinical trial aims to test the safety and efficacy of FT516 as a COVID-19 treatment. In this primary trial, the researchers want to find out the maximum dose of FT516 that can be safely tolerated in participants. The researchers hypothesize that the natural development of anti-COVID IgG in the patients will significantly increase the effectiveness of FT516 against cells infected with Coronavirus.
References
[1] NIH: NIH clinical trial shows Remdesivir accelerates recovery from advanced COVID-19 https://www.nih.gov/news-events/news-releases/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19
[2] Cao, Bin, et al. “A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19.” New England Journal of Medicine (2020).
[3] Xu, Xiaoling, et al. “Effective treatment of severe COVID-19 patients with tocilizumab.” Proceedings of the National Academy of Sciences (2020).
[4] Bryan, Jeffrey C., and Srdan Verstovsek. “Overcoming treatment challenges in myelofibrosis and polycythemia vera: the role of ruxolitinib.” Cancer chemotherapy and pharmacology, 77.6 (2016): 1125–1142.
[5] Flinn, Ian W., et al. “Combination trial of duvelisib (IPI‐145) with rituximab or bendamustine/rituximab in patients with non‐Hodgkin lymphoma or chronic lymphocytic leukemia.” American journal of hematology 94.12 (2019): 1325–1334.
[6] Dhimolea, Eugen. “Canakinumab.” MAbs. Vol. 2. №1. Taylor & Francis, 2010.
[7] Moutsopoulos, Haralampos M. “Anti-inflammatory therapy may ameliorate the clinical picture of COVID-19.” Annals of the Rheumatic Diseases (2020).
[8] Bjordahl, Ryan, et al. “FT516, an off-the-shelf engineered NK cell therapeutic product for universal anti-tumor targeting strategy in combination with monoclonal antibodies.” (2019): 3191–3191.
