A decisive turning point in the global fight against COVID-19 is that humans have obtained a vaccine. The injections have been shown to be safe, providing immunity that protects us from infection, serious illness and death.
But in many countries around the world, access to vaccines and immunizations for the majority of the population remains difficult. The number of cases and deaths from COVID-19 continues to increase in areas with low vaccination rates.
It is clear that the world needs more than one weapon to fight the epidemic. We need a drug for COVID-19, ideally a simple antiviral that can treat patients with mild to severe SARS-CoV-2 virus infection, reducing the risk of hospitalization and death. for them.
So where is this work being done by pharmaceutical companies? Bloomberg had an interview with Sam Fazeli, the head of pharmaceuticals for Bloomberg Intelligence, to shed some light on the matter.
Sam Fazeli, head of pharmaceuticals for Bloomberg Intelligence
Bloomberg: Could you tell us about the importance of antiviral drugs and how a drug to treat COVID-19 can help us manage the pandemic?
Sam Fazeli: More and more people are realizing the fact that we won’t be able to vaccinate the global population fast enough, at least as fast as we would like and should. This is partly due to the difficulty of making vaccines, even though we already have billions of doses given and there will be many more.
But more importantly, the vaccine has been distributed more widely to high-income countries. In contrast, some developing countries have extremely low vaccination rates or are using vaccines that are not as effective as mRNA vaccines from Pfizer-BioNTech or Moderna.
For these countries, having a drug that treats COVID-19 that is safe, effective, and has broad applicability would help them reduce the burden of disease and relieve some of the pressure on the system. health care while they wait for a vaccine.
These drugs can also help treat breakout cases, meaning people who have been vaccinated but still have COVID-19.
In addition, antiretroviral drugs are especially important for people whose health conditions are so weak that they cannot be vaccinated because of the risk to them. Some people may not even respond to vaccines, like people with weakened immune systems. An antiviral drug could save their lives if they are unfortunately infected with COVID-19.
By what mechanism can antiviral drugs work, sir?
The purpose of any antiviral drug is to interfere with the virus’s ability to self-replicate or replicate. This is in contrast to antibodies – whether produced by a vaccine or delivered directly – that block the entry of the virus into cells. (The vaccine also induces an immune response that seeks and destroys infected cells, thereby reducing viral replication.)
Some antiviral drugs have been developed to mimic the building blocks of material the virus uses to make up its genome, which in the case of SARS-CoV-2 is not DNA but RNA. The drug works by flooding the virus’s genome with mutations or errors, rendering its genes useless and stopping replication.
This is how a Merck drug candidate, molnupiravir (licensed from Ridgeback Biotherapeutics) is working. In addition, there are two other drugs in development and I am monitoring them:
One is manufactured by Pfizer and the other by Roche Holding AG (in partnership with Atea Pharmaceuticals). Both have the same “mechanism of action”, they block the function of an important enzyme that the virus needs to self-assemble.
Both Pfizer and Roche have shown antiviral effects in animal and cell culture studies. The drug Roche is developing has even shown some results in initial human trials, when it reduced viral loads in patients with COVID-19.
Why can’t approved therapies like antibodies or remdesivir do the job as an antiviral?
Antibodies from companies such as AbCellera Biologics, Eli Lilly & Co, GlaxoSmithKline-Vir Biotechnology and Regeneron Pharmaceuticals have proven effective in reducing hospital admissions if given early enough.
In a large trial carried out in the United Kingdom, the type of antibody “cocktails” of Regeneron have been shown to work for some hospitalized patients. But the downside of antibodies is that they are expensive and require complex manufacturing processes, often requiring several of the same materials in vaccine production.
As for the drug Remdesivir, it is only used in cases where the patient is in the hospital. Therefore, Remdesivir will not be useful as a drug to prevent severe illness and reduce hospitalizations for COVID-19.
And even if it is approved for use, the benefits of Remdesivir are marginal relative to its costs. I also note, these drugs are difficult to store and use – they are given by injection or infusion. If we successfully develop a pill, it will be a much more manageable alternative.
Are antiviral drugs susceptible to resistance to COVID-19 variants?
Almost all of the COVID-19 variants of interest now have evolved to be somewhat resistant to the developing immunity of people already infected with the virus. So they can also, although less likely, develop in people who have not been vaccinated or have had two doses of the vaccine.
Small molecule antivirals can certainly also lead to viral strains that are resistant to treatment.
The way to end viral resistance is to use two drugs with different mechanisms of action simultaneously or to use a drug that targets a part of the virus that is difficult to change or mutate. Resistance is indeed a risk that needs to be closely monitored.
Can antiretroviral drugs fight persistent, re-positive COVID-19 infections?
To answer this question, I will first cover what we are learning about vaccines. Vaccines can also have antiviral effects. New research results show that vaccination reduces persistent COVID-19 symptoms in more than 50% of people who have been vaccinated.
One theory is that the immune response to the vaccine leads to the release of persistent vesicles of the virus in the body. If that’s the case, antivirals could also help people with prolonged COVID-19 illness by helping to clear stubborn and potentially re-infective virus reservoirs.
In the event that we have such an antiviral, how do we deploy them effectively?
The good news is, it’s relatively easy to manufacture these drugs, certainly easier than making vaccines and biologicals. Many countries around the world could be transferred technology to produce such an antiviral drug.
This is the main reason why I think one or more antiretroviral drugs will be a game changer in the current COVID-19 landscape.
Easier production also leads to lower prices for antiviral drugs. Unlike vaccines, the most vulnerable populations will also be able to access antiviral drugs when they are manufactured, delivered or under the generic drug mechanism.
Indeed, Merck has made agreements with generic drug manufacturers and other pharmaceutical companies around the world to produce the drug molnupiravir.
So when will these drugs be available and “go to war”?
We now have some clinical trial data for Merck’s molnupiravir. It can clearly reduce the number of hospitalizations for COVID-19. But in the data set, there are still some ripples that make scientists unable to draw specific conclusions.
Over the next few months, we’ll get key data from the second half of Merck’s Phase III clinical trial, in addition to data on other drugs being developed by Roche and Pfizer. This will open the door to potential combinations of drugs.
If all goes well, these drugs could be made available as early as 2022.