The race toward a viable vaccine for COVID-19 has been so widely covered that it’s easy to overlook the fact that a vaccine isn’t the only solution to the current coronavirus problem.

Another acceptable outcome would be the successful development of a drug that could be used to treat COVID-19 once it’s contracted.

While an effective drug treatment wouldn’t stop the spread of the coronavirus (like a vaccine theoretically should), it would undoubtedly reduce the number of fatalities produced by the disease, which would be a gargantuan achievement in its own right.

So what are the most promising treatments for COVID-19 at present, and how far along are they in development? Luckbox has you covered.

Before diving into the specific drugs, it’s important to understand the types of treatments that are believed to have the best chance of fighting COVID-19. Listed below are the four treatment categories perceived to have the best chance of healing a COVID-19 infection, or complications related to a coronavirus infection:

• Antivirals: Antivirals are agents that kill viruses or suppress their ability to replicate. Gilead’s remdesivir, which is already approved for emergency use, is an antiviral.
• Convalescent Plasma: Plasma is a component of blood, and is essentially water that contains dissolved proteins, glucose, electrolytes, hormones, carbon dioxide and oxygen. Traditionally, treatments involving convalescent plasma hinge on removing the plasma from healthy patients who have recovered from the disease and injecting that plasma into infected individuals. This approach allows for the transfer of valuable antibodies which the recipient patient can then leverage to help fight the disease.
• Monoclonal Antibodies: Monoclonal antibodies are laboratory-produced molecules designed to mimic the natural antibodies created by the human immune system. The introduction of these synthetic antibodies in infected patients is intended to assist their immune systems in fighting the disease—much like convalescent plasma, except in this case the antibodies are synthetically produced. 
• Immune Modulators: In severe cases, COVID-19 can induce such a strong reaction from the human immune system that a “cytokine storm” is initiated. In these instances, the immune system has stopped properly regulating itself and is therefore harming the very being it was designed to protect. For example, when the coronavirus starts attacking the lungs, the immune system will send white blood cells to help fight these foreign invaders. If a cytokine storm develops, the immune system will send too many white blood cells to the lungs, which can further impair the proper functioning of the respiratory system. Immune modulators are intended to help regulate the response of the immune system to suppress the risk of a cytokine storm.

Antivirals

Gilead’s (GILD) antiviral drug “remdesivir” is the only COVID-19 treatment currently available that has received Food and Drug Administration (FDA) approval for use.

Since May 1, remdesivir has been approved for “emergency use authorization” (EUA), which means hospitals in the United States have FDA authorization to treat individuals suffering from severe cases of COVID-19 with remdesivir.

Dosing of remdesivir involves either a five- or 10-day regimen which is dependent on a given patient’s condition and the opinion of the medical team overseeing each case.

Remdesivir has been proven to assist in the treatment of individuals with moderate and severe cases of COVID-19. However, one should note that existing data suggests it is not the end-all be-all when it comes to treating the novel coronavirus.

In a study involving 600 patients, 134 of the 191 patients given a five-day regimen of remdesivir showed at least two points of improvement on the “tracking scale,” and not one of them died.

Comparing that to the control group of patients in the study who only received the current standard of care for treating COVID-19 (i.e. not remdesivir), 121 of the 200 patients in the control group also showed at least two points of improvement on the tracking scale. However, in the control group, four patients died, as compared to none in the five-day remdesivir regimen group.

The fact that no patients died from the five-day remdesivir group is likely a key reason the drug is considered beneficial for patients suffering from severe (i.e. life-threatening) cases, as well as why it has been approved for emergency use.

Additional clinical trials are still being conducted on remdesivir, which will hopefully uncover additional applications and benefits of remdesivir, but at this time its efficacy appears somewhat limited.

Another antiviral treatment to follow is EIDD-2801, which is being developed by the Drug Innovation Ventures (DRIVE) at Emory University and recently entered human testing.

Convalescent Plasma

Moving on from antivirals, the next best hope at this time appears to lie with convalescent plasma.

The goal of the plasma treatment approach is to introduce COVID-19 antibodies from a recovered patient into sick patients in order to help their bodies start fighting the virus earlier in the cycle. That’s because it can often take the human body two to four weeks to produce new antibodies, which in severe cases simply isn’t fast enough.   

However, much like remdesivir, there’s no clear evidence as yet of a guaranteed benefit from this treatment approach. That’s not to say there haven’t been successful cases in which recovered patients cite donated “survivor” plasma as a key driver behind their recovery.

However, looking at the hard data, clinical studies just haven’t provided definitive answers.

A large study conducted in China on convalescent plasma was said to have proven largely inconclusive. Another large study conducted on convalescent plasma in New York (Mount Sinai Hospital) has offered a glimmer of hope, but certainly not the panacea the medical community was hoping for.

Also referred to as “survivor plasma,” this approach has been used going all the way back to the flu of 1918, when reports from that pandemic suggested the treatment reduced the likelihood of dying.

Typically, the plasma taken from a survivor is broken up into two or three doses which are then transfused into the recipient’s blood at different intervals. However, another approach combines the plasma from several donors into a “super dose,” which relies upon a “cocktail” of antibodies to fight the infection.

The manufacturer Grifols (GRFS) is expected to start clinical trials of a super dose soon, which is commonly referred to as “hyperimmune globulin.” The Japanese drugmaker Takeda Pharmaceutical (TAK) is also investigating a potential treatment using hyperimmune globulins.

One big plus for the convalescent plasma approach is the fact that it appears to be relatively safe. The Mayo Clinic tracked 5,000 recipients of plasma through an FDA-sponsored program and found few negative side effects in those receiving transfusions.

More time and research are needed to evaluate whether survivor plasma could at some point be deemed as effective as it is safe.

Monoclonal Antibodies

The next treatment approach believed to hold a high degree of promise involves monoclonal antibodies.

As stated previously, the monoclonal antibody approach shares some parallels with the convalescent plasma approach because the goal of both is basically to introduce COVID-19 antibodies into an infected patient.

In the monoclonal approach, the main difference is that these antibodies are synthetically produced, as compared to the natural antibodies contained in the plasma.

A benefit of this approach is that it does not rely on donated plasma, which could ultimately become harder and harder to find if convalescent plasma became a go-to treatment. On the other hand, one drawback is that monoclonal antibodies are believed to only remain in the donated patient for two to three months, and not much longer.

That means a person recovering from COVID-19 using synthetic antibodies could potentially suffer another infection, although potentially a milder version.

At this time, both Regeneron (REGN) and Eli Lilly (LLY) have monoclonal antibody drug candidates that are in the early stages of development. In both cases, the drug candidates have moved beyond animal testing and are now being administered in clinical trials involving humans.

Regeneron’s candidate, known as REGN-COV2, is actually a combination of antibodies and is therefore referred to as a “cocktail” approach. Drug cocktails are often employed to ensure that a virus doesn’t adapt (i.e. mutate) and escape a single antibody, and hence utilize a second antibody as an additional level of defense to ensure greater efficacy.

Eli Lilly’s COVID-19 monoclonal antibody treatment is known as LY-CoV555, and is being developed in conjunction with AbCellera Biologics.

Immune Modulators

The first three categories of treatments for COVID-19 outlined in this post have focused on assisting the body in fighting the virus.

Antivirals attempt to weaken the virus’s ability to replicate, consequently making it weaker and more easily contained by the immune system.

On the other end of the front line, convalescent plasma (survivor antibodies) and monoclonal antibodies are both intended to try and bolster the immune system with the necessary artillery to fight the coronavirus while a patient’s immune system develops its own antibodies.

In short, antivirals theoretically weaken the virus, whereas the other two treatments are geared toward strengthening the immune response.

The fourth treatment area is focused on addressing one of the more serious adverse effects of contracting the virus: an unregulated immune response that further complicates the normal functioning of the human body.

For example, it’s well known that a huge risk of the coronavirus is developing pneumonia, or an infection/inflammation of the lungs. Pneumonia is of course dangerous in its own right, but at least there’s a long history of managing pneumonia successfully in the modern medical system.

The reason that COVID-19 is so dangerous when pneumonia develops, and also likely for those with serious pre-existing conditions, relates to the novel coronavirus’s ability to shift the body’s immune system into overdrive, meaning the immune system is working too hard to fight the disease. In some cases, patients who develop pneumonia further deteriorate when their own immune systems push more and more white blood cells into the infected lungs, making breathing even more difficult.

A patient already fighting a COVID-19 infection of the lungs must then fight their own immune system response, as the lungs fill not only with the virus, but a tsunami of white blood cells.

In the medical world, an unregulated response of the immune system which overwhelms the human body is commonly referred to as a “cytokine storm.”

As a result of this specific negative outcome, one treatment category that’s receiving a great deal of attention is immune modulators, which can theoretically reduce the risk of a cytokine storm.

Unfortunately, this is a bit of a double-edged sword, because a treatment that dampens the response of the immune system can also be a dangerous proposition.

As it pertains to COVID-19, there is consequently a “sweet spot” for the immune system—one in which it is executing its base function of protecting the body, while simultaneously regulating that response such that it doesn’t overwhelm any of the body’s critical systems.

One can see how an out-of-control immune response would not only complicate the situation of a pneumonia patient, but also patients with pre-existing conditions in which sensitive balances are thrown out of balance due to a disjointed, or irregular, response attributable to a dysfunctional immune system.

Supporting the notion that this may be a prudent course of study, an academic paper was published recently which appeared in the periodical Science Immunology that highlights how a new, experimental drug appears to have stemmed the cytokine response and led to a rapid recovery.

Additionally, there are existing drugs in various stages of development that target cytokines, and new studies are planned which will test their ability to assist patients suffering from the novel coronavirus.

Roche’s (OTC: RHHBY) drug in this category is named Actemra, while AstraZeneca (AZN) has one called Calquence.

The philosophy of this treatment approach also helps explain why treatments geared toward rheumatoid arthritis have also been tabbed as potentially effective against COVID-19. Rheumatoid arthritis is associated with abnormal functioning of the immune system, part of a broader group often referred to as “autoimmune disorders.”

Rheumatoid arthritis is often characterized by inflammation of the heart and/or lungs, which is also frequently observed in severe COVID-19 cases.

Regeneron (REGN) and Sanofi (SNY) are working together to investigate whether their existing, FDA-approved treatment for rheumatoid arthritis (Kevzara) could be effective and safe in treating COVID-19.

Parting Thoughts

Given that research into COVID-19 is still in the early stages, it’s entirely possible that drugs targeting dysfunctional immune systems, and specifically those that reduce the potential for a cytokine storm, could leapfrog other approaches in terms of potential impact.

For additional information on the performance of the broader biotechnology sector in 2020, readers may want to review a recent episode of Tasty Extras when scheduling allows.

A short-list of companies working on coronavirus drug treatments, outside of those already mentioned, include:

AbbVie (ABBV)
Adaptive Biotechnologies (ADPT)
Alnylam Pharmaceuticals (ALNY)
Amgen (AMGN)
Bayer (OTC: BAYRY)
Biogen (NASDAQ: BIIB)
CytoDyn (CYDY)
Incyte (INCY)
Novartis (NVS)
Vanda Pharmaceuticals (VNDA)
Vir Biotechnology (VIR)

Sage Anderson is a pseudonym. The contributor has an extensive background in trading equity derivatives and managing volatility-based portfolios as a former prop trading firm employee. The contributor is not an employee of luckbox, tastytrade or any affiliated companies. Readers can direct questions about any of the topics covered in this blog post, or any other trading-related subject, to support@luckboxmagazine.com.