As confirmed cases of the novel coronavirus worldwide surge over 939,436 (as of 2 April), all eyes are firmly set on the pharmaceutical and life sciences industries for the development of potential treatments.
The novel coronavirus, which causes the respiratory disease COVID-19, has overwhelmed healthcare systems and led to strict lockdowns in countries across the world as governments fight to tackle the spread of the disease.
In response to the outbreak, pharma companies have been screening thousands of compounds to identify which may have efficacy against COVID-19.
That includes both investigational drugs and approved treatments, as the search for an effective treatment grows increasingly crucial.
As the numbers climb each day, we take a look at how four of those drugs that are currently being investigated may be promising treatments against the disease that has gripped the world.
An experimental antiviral: Gilead’s remdesivir
Gilead’s remdesivir, an experimental antiviral drug, is arguably the most-talked about potential treatment for COVID-19.
Prior to the coronavirus outbreak, Gilead had primarily been focused on testing remdesivir’s potential in Ebola virus disease, although the antiviral also demonstrated promise in other coronaviruses, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).
Although the drug was eventually shelved after it failed to demonstrate superior efficacy compared to other drugs in Ebola, its potential in SARS and MERS helped it to become a focal target in the quest to find a treatment for COVID-19.
One supporter of Gilead’s drug includes Bruce Aylward, a senior advisor at the World Health Organization (WHO). During a press conference on 24 February, Aylward said that “there’s only one drug right now that we think may have real efficacy… and that’s remdesivir”.
A number of clinical trials evaluating remdesivir’s efficacy in COVID-19 are currently underway in China and the US, with Gilead CEO Daniel O’Day commenting that “initial data” is expected “in the coming weeks”.
That initial data will likely come from the studies in China, which will be closely followed by an initial report from Gilead. And although researchers are hoping for a positive result, experts are remaining cautious of an all-round win.
“I don’t think the ongoing trials will tell us a lot,” said H Clifford Lane, clinical director at the National Institutes of Allergy and Infectious Diseases (NIAID). Lane is currently overseeing ongoing studies at the US National Institutes of Health (NIH), including its remdesivir study.
“The studies might give us some hint, but I do think it will be important to get a study launched that focuses on early disease,” he added.
Although the drug is not yet approved for use against COVID-19, Gilead has plans to make the drug available via an ‘expanded access’ programme, after it had to suspend individual compassionate use requests for the drug following an overwhelming demand for the drug.
Although the compassionate use programme now only extends to children and pregnant women, Gilead said the ‘expanded access’ programme will allow hospitals or physicians to apply for emergency use of remdesivir for multiple severely ill COVID-19 patients.
“We are working at speed to establish the temporary expanded access programmes, while at the same time establishing the potential safety and efficacy of remdesivir and determining which patients remdesivir may have activity for,” added O’Day.
A combination HIV treatment: AbbVie’s Kaletra
In an unprecedented move, AbbVie has suspended its patents on its combination HIV drug Kaletra, after it was identified as having potential against COVID-19.
Kaletra combines two antivirals, lopinavir and ritonavir, and is already approved for use as a treatment for HIV.
The combination drug was first included in Chinese health authorities’ coronavirus treatment guidelines in January, thanks to early data from lab testing demonstrating its potential efficacy against the virus.
Despite the significant anecdotal evidence, an initial study of Kaletra in China demonstrated some disappointing results; it did not seem to have any significant effect on disease progression.
Although the data, published in The New England Journal of Medicine, did not show outstanding efficacy, researchers have maintained that the drug should not be discarded just yet.
That’s because for those patients who started treatment with the drug less than 12 days after their first symptoms, when they were still experiencing the early stages of the disease, the mortality rate was lower than for those who commenced the treatment later – 15% compared to 27% overall.
The reason for the disappointing results could be dependent on a range of factors, and may not solely be because the drug does not have any potential against COVID-19.
One of those factors could have been the patient population that was included in the study. Infectious disease expert Lindsey R Braden and NEJM editor-in-chief Eric J Rubin commented that “the authors chose a particularly challenging population… [who] …were late in infection and already had considerable tissue damage”.
However, the study also found that Kaletra is unable to cut viral load. This is particularity significant as the drug is designed to directly target the virus rather than alleviating the symptoms.
“Since the drug is supposed to act as a direct inhibitor of viral replication, the inability to suppress the viral load and the persistent detection of viral nucleic acid strongly suggest that it did not have the activity desired,” commented Braden and Rubin.
Either way, AbbVie is still collaborating with global health authorities to determine the extent of Kaletra’s antiviral activity, as well as its efficacy against COVID-19. Further data may offer further insight into the combination drug’s potential use against the novel coronavirus as cases continue to increase across the globe.
Evaluating IL-6 inhibitors: Roche’s Actemra and Sanofi and Regeneron’s Kevzara
Roche, Sanofi and Regeneron are also looking to repurpose their existing treatments and are currently testing their interleukin-6 inhibitors for efficacy against COVID-19.
In early March, China approved the use of Roche’s Actemra (tocilizumab) for the treatment of COVID-19 patients who develop serious lung damage, and also have elevated IL-6 levels in the blood.
The approval is based on the hope that the drug could be able to interrupt ‘cytokine release syndrome’ (CRS), a form of systemic inflammatory response that can occur as a complication of some diseases and infections.
IL-6 is a type of cytokine that plays an important role in immune response and is implicated in many diseases. Prior research has suggested that elevated IL-6 levels are associated with a higher mortality rate in people with community-acquired pneumonia.
Preliminary data from a small study of Actemra in China was promising. Treatment with the IL-6 inhibitor caused COVID-19 patients to experience rapidly reduced fevers and 75% of patients reduced their need for supplemental oxygen within days of receiving the drug.
Encouraged by this initial data, Sanofi and Rengeneron decided to take their own IL-6 inhibitor, Kevzara (sarilumab), into clinical testing for COVID-19.
The partners have already initiated trials in the US, as well as in a number of other countries including Italy, Spain, Germany, France, Canada and Russia.
The drug is being evaluated in patients who are hospitalised with severe COVID-19 and who have experienced an overactive inflammatory response in the lungs caused by the virus.
“Data from a single-arm study in China suggests that the IL-6 pathway may play an important role in the overactive inflammatory response in the lungs of patients with COVID-19,” said George D Yancopoulos, co-founder, president and chief scientific officer of Regeneron.
“Despite this encouraging finding, it’s imperative to conduct a properly designed, randomised trial to understand the true impact of Kevzara, which we are now doing through this global clinical trial programme,” he added.
A standard malaria treatment: chloroquine and hydroxychloroquine
A decades-old antimalaria drug, chloroquine, entered the global spotlight in March after US President Donald Trump touted it as a potentially effective coronavirus treatment.
Since then, the FDA has granted an emergency authorisation for chloroquine and its analogue hydroxychloroquine, despite the lack of concrete safety and efficacy data.
In a statement released by the US Department of Health and Human Services, the agency said that the drugs can “be distributed and prescribed by doctors to hospitalised teenage and adult patients with COVID-19, as appropriate, when a clinical trial is not available or feasible”.
French immunologist Didier Raoult has championed the use of the antimalaria drugs in COVID-19, after he reported that in his study of 80 patients with the novel coronavirus disease, four out of five who received treatment with chloroquine had ‘favourable’ outcomes.
An earlier study of 24 COVID-19 patients, also conducted by Raoult, found that within six days of taking hydroxychloroquine and the antibiotic azithromycin, the symptoms of the virus disappeared in three-quarters of the investigated population.
However, the French studies have been criticised due to the small study size and the lack of rigorous trial protocol, with many experts urging caution and maintaining the drugs are not miracle cures.
That caution is supported by another study from China that studied hydroxychloroquine in COVID-19 patients and found that there was no significant differences in health outcomes between the control group and patients who were treated with the drug.
Even so, a number of large-scale and rigorous clinical trials are still currently underway in the US and across the world to find if the drugs are indeed effective against the novel coronavirus.