For half a century Dexamethasone has been used to treat diseases such as rheumatoid arthritis and asthma. Four years ago, Malmö-based Aptahem was able to present preclinical data that indicate that Apta-1 in some important aspects is better than dexamethasone in hyper inflammatory conditions. A British study recently found that dexamethasone significantly reduces the risk of death from Covid-19. BioStock reached out to the company’s CSO Luiza Jedlina for a comment.
A research team at Oxford University has compared the outcome among seriously ill Covid-19 patients who received corticosteroid (cortisone) dexamethasone as treatment with those who did not.
2000 patients were prescribed dexamethasone and the treatment outcome was compared to a control group of 4000 individuals who did not receive the drug. The results, which have not yet been published in a scientific journal, showed that for patients in need of respiratory aid, the risk of death decreased from 40 to 28 per cent. For patients who needed oxygen, the risk of death decreased from 25 to 20 per cent. However, dexamethasone did not seem to help patients with milder symptoms, but only those who needed respiratory assistance.
»This is the first treatment to be shown to reduce mortality in patients with COVID-19 requiring oxygen or ventilator support« — Dr Tedros Adhanom Ghebreyesus, Director-General, WHO
June 16:th, the British Minister for Health Matt Hancock announced on Twitter that the British healthcare system will begin treating Covid-19 patients with the drug immediately. Based on the British study, the Swedish Medicines Agency also gave the green light for the use of dexamethasone in Covid-19 patients in the Swedish healthcare system.
»This is the only drug so far that has been shown to reduce mortality – and it reduces it significantly. It’s a major breakthrough.« — Peter Horby, Professor of Emerging Infectious Diseases and Global Health and Chief Investigator
Aptahem’s candidate Apta-1
Apta-1 is Swedish Aptahem’s primary drug candidate and is being developed as an emergency treatment for sepsis. Preclinical studies have shown that Apta-1 has a multifaceted efficacy profile including anti-coagulation, inhibition of hyper inflammation and tissue repair.
Taken together, the findings indicate that Apta-1 has the potential to counteract the adverse effects that occur when infections reach the bloodstream. These effects can be tissue degradation, leaking blood vessels, followed by decreased blood pressure, and life-threatening organ failure.
In 2016, the company also found that Apta-1’s anti-inflammatory effects compete with those of dexamethasone in a preclinical benchmark study but contrary to Dexamethasone Apta-1 also stimulates the production of the body’s own anti-inflammatory cytokines, like IL-10, and it is these data that are of interest in the current context.
A comment from Aptahem’s CSO
BioStock contacted Aptahem’s Chief Scientific Officer Luiza Jedlina to find out more about the now four-year-old study, and why she believes a benchmark study between dexamethasone and Apta-1 is interesting from a Covid-19 perspective.
Luiza, can you tell us more about the preclinical study from 2016 and why Apta-1 was compared to dexamethasone?
– We’ve seen in previous studies that Apta-1 had the potential of inhibiting inflammation. At that time our primary focus was anti-thrombotic treatment for stroke, but when a stroke occurs in the body so does an inflammation. The reason to compare Apta-1 to Dexamethason was to do a benchmark with an existing treatment on the market, and as this is the most commonly used pharmaceutical drug available, it was an easy choice. Also, when we got in contact with our collaboration partner Hooke Laboratories they had in vivo models already set up for this kind of comparison.
– The study showed clearly that Apta-1 had an inhibitory effect on several inflammatory factors in the body similar to Dexamethasone. The difference to Dexamethasone was the stronger ability of Apta-1 to trigger the body’s own anti-inflammatory response. Apta-1 has so far showed a very good safety profile in non-human tox studies compared to Dexamethason.
Do you think Apta-1 could substitute a dexamethasone treatment for seriously ill Covid-19 patients, and if so, why?
– Looking at the results from the UK study and comparing them with what we know about Apta-1 so far, there could preliminary be a good potential. But we of course need to test this thoroughly. We should also remember that Apta-1 could potentially cover other aspects of a Covid infection such as disorders in the coagulation system, like DIC (Disseminated Intravascular Coagulation).
»The severity of the inflammation is associated with the cytokine storm. Any drug that suppresses the inflammatory processes has the potential to improve the condition of a patient« — Luiza Jedlina, CSO Aptahem
– The patients that develop serious lung disorders following a Covid-19 infection suffer from hyper inflammation caused by cytokine storm. Dexamethason is a proven treatment for this type of inflammatory conditions. It would be interesting to test Apta-1 for the same purpose. But we have to keep in mind that Dexamethason is an already existing product on the market, and Apta-1 is still in preclinical development.
Dexamethasone is mainly used for the treatment of certain allergic reactions, inflammation associated with cancer diseases, and to counteract vomiting in the treatment of cytostatic drugs, but also for the treatment of brain swelling caused by brain tumours. Why do you think signs of increased survival have been seen in the treatment of respiratory difficulties in Covid-19 patients?
– This question should really be aimed at a medical doctor but we can speculate based on our knowledge of this area. The respiratory difficulties are symptoms of underlying severe inflammation caused by the virus. The severity of the inflammation is associated with the cytokine storm. Any drug that suppresses the inflammatory processes has the potential to improve the condition of a patient.
»Our primary focus is still sepsis, but we are always open to new collaborations where our lead candidate has the potential of being effective. But as I said earlier, keep in mind that Apta-1 is still in preclinical phase«
Finally, given the outcome of the Oxford study, do you have plans to expand the scope of Apta-1 from sepsis to also include treatment of Covid-19 patients?
– Our primary focus is still sepsis, but we are always open to new collaborations where our lead candidate has the potential of being effective. But as I said earlier, keep in mind that Apta-1 is still in preclinical phase.
The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.