Fatty acid and sweet wormwood on road to clinical trials for COVID-19

15 Apr 2020 --- Eicosapentaenoic acid free fatty acid (EPA-FFA) and extract from Artemisia annua (also known as sweet wormwood) are being investigated in the fight against COVID-19. EPAspire, the drug candidate of KD Pharma and its partner, SLA Pharma, is soon entering clinical trials as a promising candidate to treat patients with symptoms of the novel coronavirus infection. Meanwhile, ArtemiLife is collaborating with the Max Planck Institute of Colloids and Interfaces to test Artemisia annua plant extract and artemisinin (an anti-malarial drug) derivatives in laboratory cell studies.

“EPAspire is the free fatty acid form of EPA delivered to the gut by gastro-resistant capsules. Based on the speed of progression in COVID-19 patients, our researchers believe a rapid absorption of the EPA is necessary. The pharmacokinetic studies show that the product is readily and rapidly absorbed by providing EPA as a free fatty acid in its most native molecular form and bypassing the stomach,” Adam Ismail, Chief Strategy Officer at KD Pharma Group, tells NutritionInsight.

He adds that while it is not clear how consumption of EPA in other forms in a trial would differ from EPAspire, the company believes that rapid uptake of EPA should be the goal in an acute care environment like this. EPAspire is a novel oral formulation of highly purified EPA-FFA in gastro-resistant capsules, which are delivered to the gut at optimal pH allowing maximal absorption.

“This unique preparation has potential – not only to modify the COVID-19 disease process by reducing harmful, excess inflammatory responses – but also to do so without suppressing the immune response to the virus. This is vital to seroconversion giving the patient ongoing protection against continued viral challenge,” says Oscar Groet, KD Pharma’s Chief Executive Officer.

The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) approved the trial, and there are ongoing late-stage discussions with authorities in other European countries. Additionally, an application has been submitted to the US Food and Drug Administration (FDA). It is expected that the first patients in the trial will be enrolled shortly and additional hospital sites are being recruited for the trial.

Ismail notes that the timeline for a concrete conclusion depends on how fast the company can add trial sites, gain additional regulatory approvals and enroll subjects. The patients in the trial will receive the intervention for four weeks and KD Pharma will follow up two weeks after stopping the treatment. The aim is that EPAspire could help reduce the risk of mortality in severely ill patients.

“Theoretically the trial could be completed relatively quickly, but the reality is that hospitals are overwhelmed and there are many competing drugs and vaccines in trial now. We are optimistic though, because we designed the trial to fit with the existing standard of care patients are receiving. We have already received a lot of interest from hospitals around the world,” says Ismail.

EPA-FFA may modulate immune response and protect patients from COVID-19's most severe complications.Immune system modulation
EPAspire is already in European clinical trials for the treatment of familial adenomatous polyposis (FAP). Proprietary data from the FAP trials suggest it suppresses the expression of inflammatory cytokines believed to contribute to the progression of COVID-19 symptoms. Since the drug is currently in a Phase 3 trial for FAP in multiple countries, the companies have been able to initiate the COVID-19 trials very rapidly. KD Pharma notes that EPAspire’s safety profile is also well established from previous trials. 

“Some of our gastroenterologists working on the FAP trials had been called upon to help in the emergency room and with ICU patients in Italy as the crisis worsened. Based on what they were seeing and how the cytokine storm in Sars-CoV-2 infections pushes patients toward more severe outcomes, they believed this product might be valuable for COVID-19 as well,” explains Ismail. 

The primary investigators in Italy who designed the protocol believe EPA-FFA could change the course of SARS-CoV-2 infections by modulating immune response and protecting patients from its most severe complications.

Once incorporated into cell membranes, EPA-FFA significantly affects the production of pro-inflammatory mediators such as IL-6 and leukotriene B4, which play a crucial role in starting and maintaining the inflammatory process in the lungs, according to the researchers. Moreover, EPA-FFA metabolism generates pro-resolving mediators and bioactive metabolites, which enhance innate microbial killing and organ protection, they add. 

Investigating sweet wormwoodArtemiLife has already identified potential clinical partners in Europe.
Meanwhile, US-based ArtemiLife is collaborating with researchers from the Germany-based Max Planck Institute of Colloids and Interfaces. ArtemiLife notes that Artemisia annua extracts show very little toxicity, while artemisinin-based drugs are widely used to treat malaria even in newborns. Adam Maust, CEO of ArtemiLife, tells NutritionInsight that Artemisia annua extracts have previously shown activity against many other viruses, including the herpes and hepatitis viruses and flaviviruses.

“Artemisia annua contains a series of active components that interact with proteins of the host and, in turn, impact the rate of replication of the virus. An exact mechanism has not been elucidated and is likely very complicated. However, the work in cell lines will conclude the next four weeks at the very latest. If those are successful, clinical trials can be conducted immediately. In fact, we have identified clinical partners in Europe already,” explains Maust. 

“Given the encouraging results of Chinese colleagues in 2005 and similarities between the new virus and the one that caused SARS, plant extracts and artemisinin derivatives need to be tested as quickly as possible. This international collaboration makes this possible,” adds Professor Peter Seeberger, Director at the Max Planck Institute in Potsdam.

As COVID-19 claims an increasing number of lives around the globe, attention is focused on flattening the curve of its proliferation. Last month, Northwell Health, New York state’s largest healthcare provider, started to administer large doses of vitamin C to some COVID-19 patients in its hospitals, as clinical trials examining the connection between the vitamin and virus are underway in China. 

Meanwhile, an immediate investigation into the safety and protective functions of breast milk as it relates to the pandemic was recently initiated by the University of California San Diego (UC San Diego) and the Family Larsson-Rosenquist Foundation (FLRF).

Cardax has also stepped into the ring and is seeking strategic collaborations to develop astaxanthin for the treatment of COVID-19. According to the company, the carotenoid may hold promise for boosting the immune system and reducing extreme inflammatory response. Other ingredients coming under the microscope include fucoidan, coconut oil and oregano oil. 

To keep readers informed of these rapid developments, NutritionInsight has launched a daily news feed for the coronavirus-related information and insights you need to guide your business through this challenging period.

By Katherine Durrell