Heartburn drug did not halt COVID-19 - Trials continue but with larger doses
At the same time, two Danish researchers are preparing to battle COVID-19’s anticipated successors.
When COVID-19 seriously raised its ugly head in Europe in early 2020, there was an acute need for research funding to investigate a wide range of aspects of this hitherto unknown virus variant.
The Lundbeck Foundation reacted quickly and granted a total of DKK 30 million to a number of COVID-19 research projects. For instance, DKK 5 million was allocated to research into whether camostat mesylate - a long-established Japanese drug for heartburn and pancreatic infection - could halt the virus.
Two researchers from Aarhus University Hospital were behind the project: Mads Fuglsang Kjølby, associate professor at the Department of Clinical Pharmacology, and Ole Schmeltz Søgaard, professor at the Department of Infectious Diseases.
Kølby explains that although heartburn and COVID-19 may seem to have as little in common as toothache and verrucas, it makes sense to consider camostat mesylate as a potential weapon in the battle against COVID-19:
‘Ole Schmeltz Søgaard and I got the idea from an article we read in 2020 in the scientific journal Cell. German professor and virus expert Stefan Pöhlmann proved that camostat mesylate could control the spread of a so-called old variant of the coronavirus. This was the variant that resulted in SARS in a long list of countries back in 2002 and 2003. And because this old variant is closely related to SARS CoV-2 – the coronavirus that causes COVID-19 – it was an obvious step to take a closer look at camostat mesylate. It could be that this drug would also inhibit COVID-19, and that was what we applied for - and received - funds to investigate.’
Danish researchers are standing by to involve hospitals in all Danish regions in testing.
The two Aarhus researchers have now completed their trials and the results were recently published in an article in the scientific journal EClinicalMedicine, issued by The Lancet.
The bottom line is that it did not quite work out as Kølby and Søgaard had hoped. After they had collated all the numbers and measurements from the 205 patients who participated in the clinical trial, they could not prove with statistical certainty that camostat mesylate had any positive effect in the battle against COVID-19.
The drug did not shorten patients’ stay in hospital, nor did it have any effect on the severity of the disease.
In spite of this, as Ole Schmeltz Søgaard says, science has not yet given up on camostat mesylate as a treatment for COVID-19: ‘The dose we used in our trials may have been too low. In German and Japanese trials, researchers have been testing the drug against COVID-19 in much higher doses. And there are lots of us waiting on tenterhooks for the trial results.’
The patent has expired
The German and Japanese trials are being conducted by researchers from Charité-Universitätsmedizin Berlin and Ono Pharmaceuticals, respectively. Ono is the Japanese pharmaceutical company that manufactures camostat mesylate.
In layman’s terms, the underlying mechanism that makes it plausible to assume that the correct dosage of the heartburn drug will have an effect on COVID-19 is an access route. Mads Fuglsang Kjølby explains:
‘Stefan Pöhlmann was able to prove in his article in Cell that camostat mesylate inhibits the coronavirus by using a specific protein to invade the cells. The question now is whether the drug has the same inhibiting effect on COVID-19 if the dosage is increased well beyond the level we used in our trials.’
In the Danish-led trials, the participants - hospitalised COVID-19 patients - were given 600 milligrams of camostat mesylate a day for five days.
However, Mads Fuglsang Kjølby says this dosage can be increased substantially:
‘Camostat mesylate has been meticulously tested by the Japanese medicines agency, which is renowned for being very thorough and for imposing at least as stringent requirements as the supervisory authorities in Europe and the USA. In the trials currently being conducted at Charité and Ono, they give between 1,800 and 2,400 milligrams a day.’
He also says that if the researchers at Charité and Ono discover that camostat mesylate can inhibit COVID-19, the drug will be able to reach the market extremely quickly:
‘All of the documentation is in order and, what’s more, the patent has expired, so pharmaceutical companies all over the world will be able to manufacture the drug.’
Awaiting the next virus
Although the entire world is currently concentrating on keeping COVID-19 in check, researchers are in no doubt that we will see other cunning and despicable coronavirus variants in the coming years.
It is therefore important to understand in as much detail as possible how these variants attack and invade human cells - the more we know about that, the easier it will be to develop vaccines and other types of medicinal safeguard.
Together with Stefan Pöhlmann and other colleagues from Sweden, the USA, Germany, Japan and Denmark, Mads Fuglsang Kjølby and Ole Schmeltz Søgaard have also been working to map these patterns of invasion and attack.
The results of their work, which ran in parallel to the patient trials, were recently published in the scientific journal EBioMedicine.
Finally, the two Aarhus researchers are in the process of testing camostat mesylate on COVID-19 outpatients in Denmark - so, on people who have tested positive but fortunately are not ill enough to be admitted to hospital.
‘The question is whether this patient group could benefit from the Japanese heartburn drug at an early stage of their illness - in other words, whether the drug could relieve the side effects of COVID-19. However, we don’t yet have any results on this because we’re still in the process of rolling it out,’ says Ole Schmeltz Søgaard.
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A total of 205 hospitalised COVID-19 patients agreed to participate in the clinical trial with camostat mesylate, spearheaded by Mads Fuglsang Kjølby and Ole Schmeltz Søgaard. The trial was recently published in the scientific journal EClinicalMedicine.
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This was a double-blind trial.
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Two out of three patients were given camostat mesylate and the remaining third received a placebo: a calcium tablet. Neither the patients nor the doctors were aware of who received what.
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Eight Danish hospitals - in Aalborg, Aarhus, Herning, Hillerød, Hjørring, Odense, Randers and Viborg - took part in the trial. A Swedish hospital in Örebro also participated.
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If you are infected with COVID-19 and you would like to take part in the camostat mesylate trial for outpatients that is about to start up, you will find more details (In Danish) at: Camostat: Infomation about the research project
