Adequate safety testing of experimental treatments paramount even in a pandemic setting

Although there could be an extreme impulse to fast forward treatments in a pandemic setting, it is very important to conduct adequate safety checks on investigational drugs and vaccines. The treatment cannot be worse than the disease itself.

This is where repurposed drugs (existing drugs that are investigated for new therapeutic purposes) have an advantage as they often have extensive safety date backing them and are amenable to being fast-tracked. This is also, where biologics (vaccines and antibodies) have their limitations. Just because a biologic is safe in a primate model, by no means proves that it is going to be safe in humans.

Let us not forget the PAREXEL trial that went catastrophically wrong more than 14 years ago, when eight healthy young men took part in a clinical trial of an experimental leukaemia drug, TGN1412. The drug that had been shown to be safe in monkeys however led to the men fighting for their lives soon after treatment and has left some with permanent immune issues.

Having a safe treatment is especially vital in COVID-19 management when approximately 80% of people testing positive for SARS-CoV-2 may only get a mild disease.

Reference

https://pubmed.ncbi.nlm.nih.gov/17256444/

Gilead’s Remdesivir shows exceptional promise in the treatment of severely ill COVID-19 patients

''Certainly, Remdesivir appears to have come a full circle.''

Hot on the heels of the disappointing clinical trial from China in patients treated with Remdesivir as reported  in the journal Lancet, comes superbly encouraging results from a trial sponsored by the United States National Institute of Allergy and Infectious Diseases (NIAID).

In the NIAD trial, over a thousand hospitalized patients with severe COVID-19 were randomly chosen to receive either Remdesivir or a placebo. Those who received Remdesivir recovered faster than those who received the placebo (dummy) showing 31% faster time to recovery. Remdesivir also increased survival, with a mortality rate of 8% for those who received the drug and 11.6% for those on the placebo.

The Chinese trial was small, and comprised of 237 severe COVID-19 hospitalised patients who randomly received either Remdesivir or a placebo. Although the drug showed a good safety profile, Remdesivir treatment did not cause significant clinical or antiviral effects. However, interestingly the study showed that patients receiving Remdesivir had a numerically faster time to clinical improvement than those receiving placebo, though not statistically significant.

Earlier in February of this year, researchers in Wuhan had shown that Remdesivir and another drug chloroquine are highly effective in cell culture models of 2019 nCOV  the virus that causes COVID-19. In their paper, they had made a strong case for the testing of these drugs in patients saying  “Since these compounds have been used in human patients with a safety track record and shown to be effective against various ailments, we suggest that they should be assessed in human patients suffering from the novel coronavirus disease.” Certainly, Remdesivir appears to have come a full circle.

Remdesivir which began its life in Gilead Sciences under the leadership of the Czechoslovakia born Tomáš Cihlář as a treatment for Ebola virus disease and Marburg virus infections, has now proved its mettle against COVID-19. Though not a  completed cure for COVID-19, until a better drug arrives Remdesivir may well be the gold standard in the  treatment of COVID-19.

References

https://www.niaid.nih.gov/news-events/nih-clinical-trial-shows-remdesivir-accelerates-recovery-advanced-covid-19

https://www.niaid.nih.gov/news-events/nih-clinical-trial-remdesivir-treat-covid-19-begins

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31022-9/fulltext

https://www.nature.com/articles/s41422-020-0282-0

Could a drug trialled by University of Dundee researchers clampdown COVID-19?

“…we hope that brensocatib can put a brake on the devastation this disease causes, to literally stop COVID-19 when it begins attacking the lungs.” -  Professor James Chalmers

The Tay Bridge- The iconic gateway to Dundee

Dundee, the beautiful ‘city of Discovery’ in Scotland has many firsts to its role in the field of medicine. One of the early noted examples in its innovation history is the nineteenth century pivotal discovery by Thomas Maclagan, a Physician at the Dundee Royal Infirmary. Maclagan was the first to recognize the value of thermometers during a major fever epidemic, which led to reducing death rates. Today, thermometers are the bedrock of medicine and essential tools in clinical examination.

Now, Dundee may again play a crucial role in medicine, this time in the management of COVID-19 pandemic. In a major collaborative venture between researchers from Dundee University School of Medicine and Insmed, a biopharmaceutical company, the effectiveness of the drug brensocatib as a potential treatment for COVID-19  will be evaluated in clinical trials at Ninewells hospital and other sites in the country.

Brensocatib is a novel oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), an enzyme that catalyses the activation of neutrophil serine proteases in neutrophils. In a study of 300 patients receiving standard hospital care, half will be treated with Brensocatib, and the other half will receive a placebo.

About 20% of COVID-19 patients develop inflammation of the lungs, which may necessitate ventilation. Research shows that in severe cases of COVID-19, the body’s own inflammatory response meant to clear the virus goes on an ‘overdrive’ leading to lung damage, respiratory failure, and death in severe cases.

Previous studies in patients with underlying lung disease show reduction of lung inflammation by  brensocatib. The researchers hypothesise that the drug will confer similar beneficial effects in COVID-19 patients and will explore whether it can reduce the incidence of acute lung injury and prevent mechanical ventilation. They are hopeful that the treatment could reduce the patients’ dependency on oxygen support and reduce hospital stays thereby reducing the burden on an already overstretched healthcare system.

Professor  James Chalmers, a Consultant Physician at the University who leads the trial says-

 “High rates of patients requiring ventilation and overwhelming intensive care unit capacity has been a major cause of excess deaths around the world and we hope that brensocatib can put a brake on the devastation this disease causes, to literally stop COVID-19 when it begins attacking the lungs.”

https://investor.insmed.com/2020-04-23-Brensocatib-Formerly-INS1007-to-be-Studied-in-Patients-with-Severe-COVID-19-in-Investigator-Initiated-Trial

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