Accumulating evidence suggests enthusiasm surrounding Remdesivir as a treatment for Covid-19 appears warranted. Originally introduced as a treatment during the Ebola epidemic of 2013-2016, Remdesivir targeted the virus in laboratory studies and test animals. However it offered only mediocre results in comparison to other drugs in a major trial sponsored by the WHO.
During initial studies in conjunction with investigators from the CDC, NIAID and US Army Research Institute of Infectious Diseases, Remdesivir demonstrated significant activity against the coronavirus cause of the Middle East Respiratory Syndrome or MERS. Due to the small number of patients and the restricted geographic area, human testing was not undertaken. Not unexpectedly laboratory experiments of Remdesivir also revealed enhanced control of the related coronavirus resulting in Severe Acute Respiratory Syndrome or SARS.
Shortly after its debut, Remdesivir successfully treated a Scottish nurse. Her Ebola infection relapsed 9 months after apparent cure utilizing blood plasma from another nurse previously infected with the disease. The Scottish nurse’s recurrence appeared as meningoencephalitis but resolved with just 14 days of Remdesivir.
Although the WHO study ended prematurely in August 2019 without spectacular success for Remdesivir, this may ultimately prove fortuitous. Gilead Sciences, the biopharmaceutical company that created Remdesivir, maintained a stock of unused drug and a significant amount of raw material capable of manufacturing a new supply sufficient to treat thousands of patients.
Chinese investigators published the genome of SARS-CoV-2, the viral agent of Covid-19, in late January 2020. Gilead’s researchers immediately noticed the sequence for the polymerase gene almost completely matched the same region seeming conserved from both SARS and MERS. This instantly led to laboratory tests that confirmed the ability of Remdesivir to halt replication of the new virus.
Almost simultaneously contacts between the NIAID and Chinese investigators led to joint efforts to establish a potential role for Remdesivir in aiding patients stricken with Covid-19. Studies hastily arranged bonded multiple academic centers in the United States and abroad utilizing Remdesivir provided on a compassionate basis by Gilead Sciences.
The first American patient with Covid-19 received Remdesivir in late January on the seventh day of his hospitalization. He significantly improved the following day. His condition never deteriorated beyond mild-moderate illness.
The New England Journal of Medicine published the outcome of a multinational investigation on April 10, 2020. The results included 53 hospitalized patients. At entry 34 of these patients were receiving mechanical ventilation of some sort and were obviously suffering severe manifestations of the disease. Remdesivir was administered intravenously – 200 mg the first day with 100 mg scheduled for each of the subsequent 9 days.
Of the 34 most severely ill, 24% were discharged and almost 60% improved. Deaths in this group were only 18% – a level much lower than expected for comparably ill patients with Covid-19. Unfortunately there was neither a control group nor any viral studies. The results remain encouraging but not definitive.
Leaked preliminary glances of an ongoing study from the University of Chicago treating patients with severe pulmonary complications of Covid-19 appear to confirm the benefits of Remdesivir. Accidental discussion of these findings became available in mid-April. Almost all of the patients appeared to improve extraordinarily rapidly with most discharged within one week of beginning their therapy.
Compassionate / Expanded Access
From late January through late March, Gilead Sciences offered Remdesivir on a compassionate basis directed to individual patients. The effort created such a surge in demand that the company replaced if with an expanded access program available at multiple sites throughout the United States. The European Medicines Agency appears to be offering a similar model in the European Union.
Currently Remdesivir must be administered intravenously. Investigators at Gilead Science are evaluating both the oral and nasal route for symptomatic patients to potentially short circuit the need for hospitalization. Ongoing studies will determine if a 5 day course of therapy suffices rather than the currently recommended 10 day regimen.
How It Works
Remdesivir acts on viral RNA dependent RNA polymerase. This enzyme synthesized by the polymerase gene plays an essential role in the virus’s ability to replicate its nucleic acid core. Remdesivir in effect tricks the so-called RdRp into placing an analog of adenosine into the developing viral RNA strand which blocks its elongation.
Side effects seem very few in number, appear relatively infrequent and are at most bothersome rather than medically troublesome.
Ultimately if Remdesivir receives marketing approval, the company expects to profit on their investment. At present no price has been announced. Assuming the cost parallels their other antiviral therapies, sticker shock may soon follow.
At this moment Remdesivir lacks marketing approval from any regulatory agency. Public release of another favorable large study will stimulate the FDA to approve Remdesivir with dispatch. It certainly seems to be on the fast track at this moment.