Gilead Working to Scale Up Manufacturing and Approvals for COVID-19 Drug

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After reporting positive clinical trials for its COVID-19 drug remdesivir, Gilead Sciences is scaling up its manufacturing to meet expected demand while simultaneously working on an emergency authorization.

The antiviral met the primary endpoint in a U.S. National Institute of Allergy and Infectious Diseases (NIAID) clinical trial of the drug in 1,063 COVID-19 patients. Preliminary data from the trial indicate that patients receiving remdesivir had a 31% faster time to recovery than the placebo group. Patients in the placebo group had a median 15 days recovery, while patients receiving remdesivir recovered a median 11 days. The survival benefit was not statistically significant, 8% compared to 11.6% for the placebo group, although it is at least suggestive of a survival benefit.

At the same time, Gilead reported encouraging results from an open-label trial of remdesivir, the Phase III SIMPLE trial that evaluated a 5-day and 10-day dosing regimen of the drug. The SIMPLE trial showed that patients receiving the 10-day regimen had similar improvement in clinical status compared to patients on the 5-day course. No new safety issues were observed.

One of the great benefits to that is Gilead’s current stockpile of the drug will go further. In an open letter published by Gilead’s chairman and chief executive officer Daniel O’Day, he said the existing supply “amounted to 1.5 million individual doses. We had estimated that this would be 140,000 treatment courses based on a 10-day treatment duration. The ability to shorten duration for severely ill patients means we can significantly increase the number of courses available, all of which Gilead has committed for donation.”

The company is working to build a global consortium of pharma and chemical manufacturers in order to expand global capacity and production. They are also working with regulators on emergency use authorizations for the drug.

However, the company’s chief financial officer, Andrew Dickinson, warned at a first-quarter earnings conference call that some of the ingredients used to make remdesivir are hard to come by and the company is being careful not to cause problems in its own supply chain, which is the fastest path to getting the drug to patients.

The company believes it can get more than one million treatment courses manufactured by December 2020, with plans to produce several million in 2021. It plans to donate the current 140,000 courses that it expects to manufacture by the end of May.

The drug is intravenous and initially took close to a year to manufacture. They have since cut the time down, but it is still a lengthy process. It requires a series of chemical reactions that need to be completed in a specific sequence with a manual inspection of each vial at the end of the process. Some of the steps require unique ingredients with limited supplies and several of the steps can take weeks.

“It’s not just the active ingredient — there are additives,” said Bernhardt Trout, a professor of chemical engineering at MIT. “Those have to be pharmaceutical grade and safe and tested. Every time you get an ingredient, you have to test that and make sure it falls within specifications. You have to analyze impurities. You have a quality control system. You have to then scale up your process to make millions of doses or whatever it is, and show that your process is robust because there are always variations.”

The company is also investigating the possibility of subcutaneous and inhaled formulations of the drug, although there is currently no timeline on that or if it will even be possible. The company indicates that because of how the drug is metabolized in the liver, there will be no pill or tablet formulation.

At this point, remdesivir is still an experimental drug. It has not been approved for clinical use, although it has been approved for compassionate use. The company is working with the U.S. Food and Drug Administration (FDA) on an emergency approval, and with the European Medicines Agency (EMA), which has begun a rolling review of the remdesivir data. The EMA’s rolling review program lets the agency evaluate data as it becomes available instead of waiting for all of the information. The EMA reportedly has not committed to a date on approval, although it did say it expected to “complete its assessment significantly earlier” than if it had undergone the traditional review process.

The FDA’s process is similar, but appears to be more likely to occur imminently, whereas the EMA may take a bit longer. Still, there’s quite a bit of pressure on the part of regulators to get the drug to patients as soon as possible.

In its first-quarter financial report, Gilead indicated that it has spent around $50 million on research and development around remdesivir in the first quarter, which is about 4.5% of its total R&D spend. O’Day indicated that the company will work to create a sustainable business model for the drug going forward to ensure it is affordable and accessible to patients around the world that need it.

“We are conscious of the fact that this is different, that it is unique,” he said, when asked if investors would see similar profit returns to what it has seen on its drugs for HIV and hepatitis B. “There is no rule book out there other than we need to be very thoughtful about how we provide medicines to patients around the globe, and do that in a sustainable way.”