Drugs Against CoViD-19

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Til August 31st, 2020 there is no cure drug against Covid-19. Vaccines could be best to tackle this viral disease. I wrote down this post on April 24th, and I am actively updating this post. 

 

• Hydroxy-chloroquine (HCQS)

This old antimalarial and DMARD drug saw massive support from ICMR and US President Trump. People started taking it as prophylaxis without any proven benefit in prophylaxis. Trials in China also showed no proven benefit i.e. faster recovery with HCQS. In vitro studies showed that HCQS kills the virus. 


In June, 2020 WHO says it is not working, and then again says we are continuing the trials to confirm it can reduce Covid-19 symptoms. 

I am not going to write down the dose how Indian doctors are prescribing it to patients, as it would create self prescribing but it is given as pre-exposure prophylaxis and some data says those on PrEP are often asymptomatic. Those patients with contact history are also given a short course of HCQS. 

A ICMR data showed HCQ may be beneficial for HCPs (media report). 

• Lopinavir/ritonavir (Kaletra) 

The combo is generally used as anti-retroviral therapy among HIV+ patients. In some trials it shows promising results against Covid-19. It has proteolysis activity. 

[Primary outcome - time to clinical improvement; Secondary outcome - mortality, ICU stay, viral load] Dose: Lopinavir/Ritonavir (400/100 mg) twice daily x 14 days. 

Chinese trial says no benefit was observed with lopinavir-ritonavir treatment beyond standard care (Link)

• Umifenovir (Arbidol) - This antiviral is used against influenza in China and Russia. By mid-June, Umifenovir is in clinical trials in India.

• Tilarone - This broad spectrum antiviral, is being used in Russia and other federation countries against multiple viruses, including acute respiratory viral infection, influenza, and hepatitis.

• Remdesivir -This Gilead-made antiviral drug was actually made against Ebola virus. It inhibits viral RNA polymerases by activating nucleoside triphosphate metabolite. It prevents the replication of viral RNA in vitro. Few patients of famous cruise ship in Japan was given Remdesivir in US with some success. 

In May '20 Remdesivir is the only drug approved by United States Food and Drug Administration (USFDA) for Emergency Use Authorisation (EUA) treatment of adult and paediatric patients hospitalised with suspected or laboratory confirmed COVID-19 infection. 

In India initially Remdesivir was available through black market. But soon Indian pharma companies had started to launch their own branded Remdesivir. 

 ⇒ Hetero's remdesivir of 100mg Covifor at Rs 5400

 ⇒ Mylan's DesRem at Rs 4800 

 ⇒ Jubilant Generics Ltd - Jubi-R at Rs 4700

 ⇒ Cipla - CipRemi at Rs 4000 

 ⇒ Zydus Cadila - Remdac at Rs 2800 

• Favipiravir (brand name Avigan) - This antiviral drug was developed by Toyama Chemical of Fujifilm group, and got approval of use in Japan in 2014. It became a generic drug in 2019. 

Since April 2020, Favipiravir is being used for nCoV-19 infection in China.  Favipiravir, a purine nucleic acid analog and potent RdRp (RNA-dependent RNA polymerase) inhibitor was approved for use in influenza (similar to Oseltamivir). Researches have showed that Favipiravir may able to control symptoms i.e. faster remission in mild to moderate COVID-19 cases. 

In June end, 2020, Glenmark launched it in India at Rs 103 per tablet of 200mg. 

Soon after Glenmark's launch of favipiravir in India, several pharma companies launched their favipiravir at reduced prices. Glenmark too reduced price to Rs 75 per 200mg tablet.

⇒ Glenmark - Flaviflu @Rs 75 per 200 mg tablet

⇒ Brinton - Flaviton @Rs 59 

⇒ Jenburkt - Flavivent @Rs 39

⇒ Cipla - Ciplenza @Rs 68

⇒ Hetero - Favivir @Rs 59

⇒ MSN - Favilow @ Rs 33

⇒ FDC - PiFLU/Favenza @ Rs 55

• Tofacitinib (Xeljanz) - A JAK 1 / 3 inhibitor from the house of Pfizer, Tofacitinib is being used as an anti-RA drug, approved by FDA in 2012 is also a possible candidate against Covid-19.

• There has been update that plasmapheresis also tried to counteract cytokine storm. Human convalescent plasma with a SARS-CoV-2–specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19 and transfused in 5 critically ill patients after 10-22 days of admission and all are recovered. 

Source: https://jamanetwork.com/journals/jama/fullarticle/2763983

• Tocilizumab, an IL-6 inhibitor, is on phase III trial by Roche (Actemra | COVACTA trial) - to counteract cytokine release syndrome in severe lung damage cases which has worst prognosis. Tocilizumab is currently indicated for the treatment of various Rheumatological disorders like Rheumatoid Arthritis, Systemic and Polyarticular Juvenile Idiopathic Arthritis. 

Severe form of COVID-19 is often associated with IL-6 mediated Cytokine Release Syndrome (CRS), causing symptoms like high fever and hypoxic pneumonitis. 

In India Tocilizumab is yet to be approved for COVID-19 in India, therefore the use of Tocilizumab in severe COVID-19 is restricted and must be done after weighing risks and benefits. 

In India, Roche Products (India) Pvt. Ltd. is importing Actemra and Cipla is marketing and distributing Actemra.

• Ruxolitinib (Jakafi) - There is another way to block IL-6 via inhibiting receptor signal transduction by JAK (Janus Kinases 1/2). Example is Ruxolitinib, but it can affect the host’s antiviral immunity mediators such as natural killer cells, dendritic cells, and beneficial cytotoxic T lymphocytes as well as deleterious effects on cytokines such as IL-2, IL-7, and IL-15. It is now approved for use in myelofibrosis and polycythemia vera. 

• Baricitinib - Another JAK Inhibitor (JAK 1/2), Baricitinib also neutralizes protein AAK1, which can facilitate entry of SARS-CoV-2. BenevolentAI, the UK-based AI drug discovery company initially identified baricitinib as a potential treatment using its machine learning system.

• Other JAK inhibitors - Fedratinib, Pacritinib

• Ivermectin - Ivermectin is approved for parasitic infections, and it's is repurposed for COVID-19 treatment, as it is shown to cause ~ 5000 fold reduction in SARS-CoV2 at 48h in cell culture. Dr Md Tarek Alam of Bangladesh is conducting trial with antiprotozoal Ivermectin and antibiotic Doxycycline in COVID-19 patients. In Australia there is a trial of Ivermectin, Doxycycline and Zinc. 

• Merimepodib - it is a broad spectrum antiviral. It is being tested with Remdesivir, the trial is in phase II. 

• Inhaled interferon beta - UK based Synairgen has developed inhaled formulations of interferon beta, SNG001, and small clinical trial with it showed positive results. 
• Hanfangchin A (tetrandrine) - a chloroquine dervivative, currently on phase III trials.
• Astemizole - An antihistamine was withdrawn from market due to fatal side effects, now again being testing against COVID-19.
• Clofazamine - An anti-leprosy drug.

• Mavrilimumab - A single-centre prospective cohort study, based on San Raffaele Hospital, Milan, Italy shows mavrilimumab may be another choice in treating severe COVID-19 pneumonia and systemic hyperinflammation. Mavrilimumab is an anti-granulocyte–macrophage colony-stimulating factor (GM-CSF) receptor-α monoclonal antibody. It was given as single IV dose of 6 mg/kg on top of standard care. 

Given its cardinal role in innate inflammation, GM-CSF may be a potential mediator of the cytokine storm. Atypical pathogenic T helper 1-cells expressing GM-CSF have been identified in patients with more severe COVID-19, but not in those with less symptomatic patterns and in healthy controls.


  ✘ Sarilumab 
Regeneron and Sanofi also initiated trial for Sarilumab (Kevzara), another IL-6 inhibitor. On September 1, 2020, Sanofi announced they are to stop conducting further clinical studies for Kevzara in COVID-19, as it fails to reach primary and secondary key endpoint. 

This article will be updated from time to time. 

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