Gilead Sciences Races to Manufacture Remdesivir, but Chemistry Has Speed Limits - Motley Fool

The world is eagerly awaiting results from hundreds of clinical trials searching for treatments for COVID-19, the respiratory disease caused by the SARS-CoV-2 virus. Much like stay-at-home orders were issued to buy time for health systems and medical supply chains to prepare for possible surges in hospital admissions, effective treatments would buy time for the world to develop and manufacture effective vaccines.

One of most closely watched drug candidates is remdesivir from Gilead Sciences (NASDAQ:GILD). When promising data leaked from an ongoing clinical trial, the pharma stock soared. It's certainly a promising development at a time when the world could use some good news.

But proving remdesivir is a safe and effective COVID-19 treatment (which hasn't happened yet) is only the first step. Gilead Sciences must secure supply chains, ramp-up manufacturing capacity, and distribute the drug throughout the world. That might prove more difficult than investors realize.

A scientist looking through a microscope.

Image source: Getty Images.

Could remdesivir become an effective COVID-19 treatment?

Perhaps. The digital publication STAT, which provides healthcare news and commentary, obtained a video from the University of Chicago Medicine discussing interim results from an ongoing clinical trial. The center is one of many participating in a larger clinical trial evaluating remdesivir as a treatment for COVID-19.

The site enrolled 125 patients individuals with COVID-19, including 113 in severe condition, to receive daily infusions of remdesivir. Many of the patients had been safely discharged from the hospital, and only two had died at the time the comments were made. Severe fevers dissipated quickly, while other patients have been removed from ventilators shortly after starting therapy.

Most importantly, many patients were discharged from the hospital in six days. Gilead Sciences has been studying 10-day courses of remdesivir to treat COVID-19. Treating patients for a shorter duration could allow the company to stretch a very limited supply of the drug, which is likely to be the biggest bottleneck.

What obstacles is Gilead Sciences staring down?

As of January 2020, Gilead Sciences wasn't actively manufacturing remdesivir because the drug candidate had never been commercialized. The company had enough finished product for 5,000 patients assuming a 10-day course of treatment.

After watching a coronavirus outbreak put China on lockdown, Gilead Sciences raced to secure the rare materials and production capacity required to manufacture the antiviral at scale. The biotech reduced the manufacturing ramp-up timeline from a range of nine to 12 months to an estimated six to eight months, and it's working to optimize the complex chemistry required to manufacture the drug candidate.

But there are speed limits:

Complex chemistry: Antivirals -- commonly identified by the suffix "-vir" -- are generally very difficult to manufacture at scale. Production processes are hindered by many complex organic chemistry steps that must be completed sequentially, are accompanied by low yields, and require ultra-rare chemical inputs with very limited global supply. The latter might be the most important limiting factor for remdesivir production.

Strict sterility requirements: Drugs that are administered intravenously (IV), such as remdesivir, must be manufactured in specialty drug compounding facilities under strict sterility conditions. The world has limited production capacity.

Volume: Manufacturing antiviral drugs under normal conditions is difficult enough, but the time crunch of a global pandemic adds a new twist. Gilead Science will face pressure to manufacture enough remdesivir to treat tens of millions of individuals, which might be an impossible task.

How many courses of treatment could be manufactured?

Gilead Sciences has significantly increased the amount of remdesivir on hand and made strides to bring future production capacity online in North America, Europe, and Asia. It still might not be enough to make the antiviral the world's only COVID-19 treatment. Consider the company's current forecast for production based on treatments spanning 10 days (the initial expectation) and five days (an endpoint in newer clinical trials).

Date	Patients Treated with Available Product (10-Day Treatment)	Patients Treated with Available Product (5-Day Treatment)
January 2020	5,000	10,000
Late March 2020	30,000	60,000
End of May 2020	140,000	280,000
By October 2020	500,000	1 million
By December 2020	More than 1 million	More than 2 million
In 2021	Several million	Several million

Data source: Gilead Sciences, author calculation.

This limited supply will be saved for hospitalized patients. Based on currently available data, it appears that roughly 15% to 20% of confirmed coronavirus cases require hospitalization. The real number is likely much lower once asymptomatic cases are factored into the calculation, but scientists have no way to gauge the number of asymptomatic cases at this time.

For the sake of simple math, the current 15% hospitalization rate implies several million doses of remdesivir would be sufficient for every 20 million confirmed coronavirus cases. As of April 22, there are 2.6 million confirmed coronavirus cases globally, although that low number represents limited testing capacity and the positive effects of stay-at-home orders.

Luckily, there are several things that could relieve pressure on Gilead Sciences -- and even help to significantly increase production of remdesivir.

A woman talking to a nurse via telemedicine.

Image source: Getty Images.

Can anything reduce supply pressures on remdesivir?

Doctors are still learning about COVID-19, but some of the mystery is beginning to fade. For example, emergency room doctor and intubation instructor Dr. Richard Levitan recently wrote in The New York Times that monitoring oxygen levels, even in patients without breathing issues, can significantly reduce the need for intensive care and mechanical ventilation. That small change could help a limited supply of eventual treatments go further.

Meanwhile, hospitals around the world are beginning to test whether plasma from recovered COVID-19 patients can limit the severity of disease in current patients. It will become easier to harvest plasma as more patients recover. If plasma therapy proves effective, then it will be another arrow in humanity's quiver aimed at reducing the impact of the coronavirus pandemic.

Gilead Sciences could also make a Hail Mary investment to significantly increase the production of remdesivir: enzymes. These are the complex proteins that power all living things. Enzymes are used to speed up, clean up, and increase yields of chemical reactions within the settings of biological cells all the way up to industrial chemical production. They've garnered tremendous interest from pharmaceutical companies manufacturing antivirals.

For example, Merck and Codexis recently proposed a novel manufacturing process for the experimental HIV drug islatravir, which belongs to the same class of drugs as remdesivir. The pair engineered five enzymes to simplify the complex organic chemistry required to produce islatravir. In the end, time-consuming purification steps were eliminated, ultra-rare raw materials were recycled, yields of the final drug product were significantly increased, and the number of total production process steps was reduced by more than half.

On paper, enzymes could be used to significantly increase the yield of remdesivir while reducing overall inputs and, importantly, reducing the importance of ultra-rare chemical inputs with limited global supply. In reality, it would be very challenging for Gilead Sciences to engineer enzymes specific to remdesivir synthesis, incorporate them into new production processes, and scale those production processes in the compressed timelines it faces.

But if there was ever a time for synthetic biology to live up to its lofty potential through a global collaborative effort, now might be it.

Clinical trials are only the first step for remdesivir

Investors might be encouraged by the leaked data from part of a remdesivir clinical trial. If the antiviral proves safe and effective in reducing the severity of COVID-19 infections, then it could buy significant time and free considerable resources as humanity awaits more permanent solutions, such as vaccines.

But investors have to remember that there's only so much Gilead Sciences can do to scale production of remdesivir to the volumes likely to be demanded or required in the timeline available. The drug candidate could still become a historic success in public health, but it's unlikely to become the only COVID-19 treatment humanity pins its hopes on.

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