From The Editor | May 12, 2020

Regeneron's COVID-19 Trial Reaches Patients In 5 Days

Ed Miseta

By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical

Vials Blood Test

In just a few months, COVID-19 has made an impact in almost every country around the world. At the end of April, the pandemic had already been blamed for over 227,000 deaths. As physicians face rising numbers of COVID-19 cases, they are also trying new and innovative solutions to try and save lives. One option is repurposing existing drugs to target the virus.

At AdventHealth, a multi-state care network with more than 50 hospitals, two such treatments are being deployed to treat its most seriously ill COVID patients. Dr. Steven Smith, chief scientific officer for AdventHealth, notes those two drugs are remdesivir and sarilumab. To receive the treatments, patients must be in the ICU and receiving oxygen support.

“Remdesivir was originally developed to treat the Ebola virus and sarilumab (Kevzara) is a treatment for moderate to severe rheumatoid arthritis,” says Smith. “Due to the urgency of the COVID-19 pandemic, the FDA is allowing hospitals to deploy drugs outside of their officially approved uses.”

The Search For A Treatment

Leading medical institutions across the country, including AdventHealth, are administering sarilumab as part of a clinical trial to determine its effectiveness against COVID-19. The drug is approved to reduce inflammation in joints, and researchers hope it might have the same benefit in reducing inflammation of the lungs. The science revolves around a condition in patients known as a cytokine storm, which means a body will go into a hyperinflammatory mode. If sarilumab can suppress that response, it may prevent injury to the lungs and other parts of the body.

Dr. Steven Smith, chief scientific officer, AdventHealth
Dr. Steven Smith, chief scientific officer, AdventHealth
According to Smith, reports out of China and later Italy made note of the cytokine storm process. 

A search was conducted that looked at drug portfolios and medicines in development for other indications that could be used against a cytokine storm. AdventHealth began talking to pharma companies with potentially helpful treatments, and that led them to Regeneron Pharmaceuticals. The organization was pleased to learn Regeneron already had an ongoing trial examining the impact of sarilumab on COVID symptoms, and opted to include patients in the trial.

AdventHealth’s most serious patients were in the ICU and needed immediate help. For that reason Smith and his colleague, Dr. Amay Parikh, wanted to administer the treatment to patients as quickly as possible. Parikh is medical director of the Neuro ICU at AdventHealth Orlando and site principal investigator for the trial.

“We were able to get this trial up and running in a record period of time,” states Smith. “This is a blinded, randomized trial and we did not know if the treatment would work, but we were eager to try something that could fight the cytokine storm that was impacting our patients. We implemented a process whereby everyone worked aggressively and with a laser focus to get the trial opened safely and effectively in a minimal amount of time. The process has even been formalized for use in the future. We signed the documents with Regeneron and were administering the drug to our patients in less than five days.”

Despite the quick startup, Smith notes AdventHealth had not worked with Regeneron on other studies. However, everyone knew patients required a treatment quickly, and Regeneron was willing and eager to fast-track the site initiation process. More than 35 patients have already been treated and Smith notes more patients continue to be added. AdventHealth is now close to hitting its enrollment goal.

“Our ability to make this happen required a highly-functioning clinical trial, infrastructure, and the sponsor being eager to move quickly,” says Smith. “We always try to initialize a trial as soon as possible, but with the pandemic and the surge of patients in our hospital systems, the need to move fast became more imperative.

Reallocate Your Resources

Bari Kowal, VP and head of global clinical operations, Regeneron Pharmaceuticals
Bari Kowal, VP and head of global clinical operations, Regeneron Pharmaceuticals
Bari Kowal, VP and head of global clinical operations for Regeneron, notes it generally takes months to move from trial concept to enrollment of the first patients. The COVID-19 trial for sarilumab was completed in a matter of days, even with members of her team working remotely. The task required Regeneron’s clinical team to be nimble. When the decision was made to start this trial for patients of the pandemic, Kowal took internal resources and reallocated them to the trial.

The rapid execution of this trial also required the commitment of the FDA, which worked with Regeneron’s leadership team over a weekend to review the trial protocol. “Equally critical was the terrific collaboration with other groups including the Biomedical Advanced Research and Development Authority (BARDA), our partner Sanofi, and healthcare facilities and clinical trial sites across the country,” says Kowal. “We certainly wouldn’t be where we are today if it wasn’t for the doctors, nurses, scientists and others who worked with us around the clock to carry out this trial in an unprecedented setting.”

In addition to the U.S. trial, the clinical trial program was initiated in Italy, Spain, Germany, France, Canada, Russia, Israel and Japan by Regeneron’s partner Sanofi. 

Facilitate Site Engagement

One of the amazing accomplishments in fast-tracking this trial was Regeneron’s ability to quickly onboard sites. The company was able to open 50 sites in just 2 weeks, and a few of those sites were opened in under 48 hours. According to Kowal, that effort required an incredible amount of work. Therefore, Regeneron had to be smart in how it organized and directed its team. The team also had to identify and onboard an IRB, in addition to multiple vendors for laboratory supplies and randomization services.

“The willingness of our team members to be reallocated to lead and manage this trial was critical to our success,” states Kowal. “That enabled us to circumvent the need to onboard external teams and align processes with a CRO. We also initiated a central IRB and standardized study materials and budgets as much as possible to allow for a rapid review process. Additionally, we worked closely with our Industrial Operations & Product Supply teams to secure the drug supply and coordinated with our logistics group to get product to the clinical sites as expeditiously as possible. The driving force was the desire to find an effective treatment, and teams on all sides worked tirelessly to ensure a streamlined start-up process”

Smith notes there has been many discussions in the press around COVID-19 and possible therapeutics. He notes the physicians and clinicians at AdventHealth team understand clinical trials require robust data. That is true of any clinical trial and COVID-19 in no different. A lot of anxiety exists because of the pandemic, and there is a desire for researchers to move fast.

“We are moving this trial and others as fast as we can, but we still need definitive answers,” he says. “At this time, randomized controlled trials are still the only way to achieve that. This trial has commitment from all of our key stakeholders and thus far we have been bowled over by the positive responses.”

Kowal agrees. “At Regeneron, we believe the solution to COVID-19 is not going to be a single medicine by a single company. It’s going to take a collaboration of local governments, regulators, biotech companies, and hospitals to put aside different viewpoints and work together. We’re honored to be part of this effort.”