Out of Africa: Remdesivir's extraordinary journey to COVID-19

Out of Africa: Remdesivir's extraordinary journey to COVID-19
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It is a tale that spans continents, with heroes, heroines and a moral about our shared humanity. This is the story of Remdesivir, the anti-viral drug showing promise in the fight against COVID-19 — offering up the first glimmer of scientific hope against a global pandemic that has claimed more than 60,000 American lives and 200,000 globally.

In 2009, researchers at Gilead Sciences of Foster City, Calif., developed the antiviral compound Remdesivir as a possible treatment for Hepatitis C. Unfortunately, it was not effective, and remained in closed research until 2014, when the deadly Ebola virus emerged in Sierra Leone, Liberia and Guinea.  

For the first time since the discovery of the virus in 1976 in the Congo basin, Ebola went urban in West Africa, and there were no effective treatments, with patients left to rehydration therapies and symptom management, with a single experimental therapeutic exception.

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In July 2014, Dr. Ken Bradley, 33, an American running one of the few Ebola Treatment Units in Liberia for Samaritan’s Purse, caught Ebola. Near death, with the whites of his eyes bleeding, Bradley was administered an experimental antiviral treatment called ZMapp. Within hours, the virus stopped its relentless replication, Bradley stabilized, and was flown to the United States where he fully recovered. Others were not so lucky. 

Sierra Leone’s top doctor, Dr. Sheik Umar Khan, who treated over 100 Ebola patients, also contracted the disease, but ZMapp arrived too late to save him, as it did for Samuel Brisbane of Liberia who fell ill treating patients at the John F. Kennedy Memorial Hospital, and in August 2014, ZMapp developer Mapp Biopharmaceutical ran out of supply.

The Ebola virus spread out-of-control through the summer months of 2014, with these governments struggling to care for the sick and bury their dead. Finally, in September, at the margins of the United Nations General Assembly, a belated international response was mobilized through the United Nations Mission for Emergency Ebola Response (UNMEER). The United States sent the 101st Airborne to Liberia to help establish a logistical bridge, and the U.S. Congress passed a $4.6 billion urgent supplemental appropriations for Ebola response, recovery and preparedness. 

Enter Remdesivir.

As part of the urgent supplemental funding from Congress for Ebola response, Gilead got another shot at trying out the efficacy of its Hepatitis C compound, this time as a potential treatment for Ebola, working in partnership with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), the only Department of Defense facility with Bio Safety Level 4 capabilities.

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On Oct. 15, 2015, USAMRIID, in collaboration with the U.S. Centers for Disease Control and Prevention (CDC), announced that in preclinical results, Remdesivir had blocked the Ebola virus in Rhesus monkeys. The report noted that initial screening of the compound found promising antiviral activity.  

Unfortunately, it was not until early 2016 that Remdesivir was offered for compassionate use in humans, and by that time, the disease had burned out in the subregion, and there were not enough patients left to conduct a scientific clinical trial. More than 11,000 people died across Sierra Leone, Guinea and Liberia, roughly 2 out of every 3 who were infected. 500 healthcare workers lost their lives.

Two years went by, then in August 2018, Ebola returned to the Democratic Republic of the Congo (DRC), but this time in the eastern region, a zone of instability controlled by rebel groups and tribal militias, making disease response perilous.

Despite the security threats, the government of the DRC worked with researchers from the U.S. National Institute of Allergy and Infectious Diseases (NIAID) of the National Institute of Health (NIH), the World Health Organization (WHO), and other non-governmental organizations, to devise a clinical trial of four therapeutics. There were no placebos. Every person who participated received one of the treatments.

Remdesivir and ZMapp were introduced into the DRC clinical trial along with mAb114 and REGN-EB3, two monoclonal antibodies, and as it turned out, Remdesivir was the least effective of the four, with nearly half of those receiving it dying. But REGN-EB3 scored a 94 percent recovery rate — Ebola was now effectively a treatable disease!

While Remdesivir came in last in the race to cure Ebola, it was in play and was proven to be effectively tolerated in the at-risk population, a milestone in and of itself for a clinical trial.

The rest is recent American history: Remdesivir, a drug that failed for Hep. C and Ebola, has emerged as a promising treatment for COVID19. Dr. Anthony Fauci, director of NIAID, explained while not a "knock out," the study results were "a very important proof of concept."

Much credit goes to Gilead’s scientists and researchers for their perseverance with a drug that failed twice. But they didn’t do it alone.

Research in neglected infectious diseases is not a profitable pursuit; it’s only enabled by the generosity of others, including the American people. Since 2003, $90 billion dollars has been appropriated for the President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund, saving millions of lives — and today providing the backbone upon which African nations are responding to the COVID19 pandemic. The U.S. remains the single largest bilateral donor in global health, and PEPFAR the most ambitious program of its kind.

In the end, scientists and appropriators aside, the real heroes and heroines of the Remdesivir story are the front-line healthcare workers: Drs. Khan, Brisbane, Bradley, other medical professionals, nurses, midwives, the community mobilizers and — of course — the tens of thousands who grew sick and died, each who helped to conceive the urgency for scientific discovery to save the next generation of lives.

We don’t know yet what the closing chapter of the Remdesivir story will be, but we can hope — and what we can say for certain is that our fight against Ebola may very well have delivered for the American people on COVID19. And as for the moral of the story, that is clear: In helping others, we helped ourselves.

K. Riva Levinson is president and CEO of KRL International LLC, a D.C.-based consultancy that works in the world’s emerging markets, award-winning author of "Choosing the Hero: My Improbable Journey and the Rise of Africa's First Woman President" (Kiwai Media, June 2016). You can follow her @rivalevinson