Remdesivir reportedly flopped in Chinese COVID-19 study - yet controversial
Dear Editor,
Earlier this month, a study in the New England Journal of Medicine showed early positive results for remdesivir, developed by California-based Gilead Sciences, with 68 percent of patients improving on the drug [1]. However, the study was not an official trial but rather the collation of data from patients who had been given the drug on a “compassionate use” basis — and was not compared to any control arm. In this study of hospitalized adult patients with severe Covid-19 that was terminated prematurely, remdesivir was not associated with clinical or virological benefits. The scientists behind the study and Gilead warned at the time that it was not conclusive.
Remdesivir has flopped in its first randomized clinical trial, disappointing scientists and investors who had high hopes for remdesivir, according to draft documents published accidentally by the World Health Organization and seen by the Financial Times [2].
After Gilead agreed, Chinese doctors launched two formal studies of remdesivir; one in severely ill patients, and another in people with milder disease. Both studies compared the drug to a placebo. But in mid-April, both were suspended when scientists could not enroll the more than 400 patients needed for each trial. The Chinese trial showed remdesivir did not improve patients’ condition or reduces the pathogen’s presence in the bloodstream. Researchers studied 237 patients, giving the drug to 158 and comparing their progress with the remaining 79. The drug also showed significant side effects in some, which meant 18 patients were taken off it.
“Importantly, because this study was terminated early due to low enrolment, it was underpowered to enable statistically meaningful conclusions.”
“As such, the study results are inconclusive, though trends in the data suggest a potential benefit for remdesivir, particularly among patients treated early in the disease.”
The WHO collates current trials for possible Covid-19 interventions on a website titled “landscape analysis of candidate therapeutics for Covid-19.” A previous version of the website, which contained five pages and a column called “outcomes,” is no longer available. The new one only contains four pages and no “outcome” column.
The WHO said the draft document, which is undergoing peer review, was published early in error. “In response to WHO asking for information and studies to be shared early, a draft document was provided by the authors to WHO and inadvertently posted on the website and taken down as soon as the mistake was noticed.”
There are multiple ongoing Phase 3 studies that are designed to provide the additional data needed to determine the potential for remdesivir as a treatment for Covid-19 [3]. These studies will help inform whom to treat, when to treat and how long to treat with remdesivir. The studies are either fully enrolled for the primary analysis or on track to fully enrol in the near future.
A recent US National Institutes of Health animal study also found the drug was effective at treating the disease in monkeys when taken early in its progression [4].
Gilead expects to release preliminary data from a late-stage study of the drug in treating patients with severe cases of COVID-19 by the end of April. Initial data from a National Institutes for Health study and Gilead's study focusing on patients with moderate symptoms of COVID-19 will be announced in May.
References:
1. Grein, J., Ohmagari, N., Shin, D., Diaz, G., Asperges, E., Castagna, A., Feldt, T., Green, G., Green, M.L., Lescure, F.X. and Nicastri, E., 2020. Compassionate use of remdesivir for patients with severe COVID-19. New England Journal of Medicine.
2. Gilead antiviral drug remdesivir flops in first trial. Financial Times, (https://www.ft.com/content/0a4872d1-4cac-4040-846f-ce32daa09d99)
3. https://clinicaltrials.gov/
4. Williamson, B., Feldmann, F., Schwarz, B., Meade-White, K., Porter, D., Schulz, J., van Doremalen, N., Leighton, I., Yinda, C.K., Perez-Perez, L. and Okumura, A., 2020. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. bioRxiv.
1 Faculty of Pharmacy, The Islamia University of Bahawalpur, Pakistan; 2 Faculty of Pharmaceutical Sciences, GC University Faisalabad; 3 Nishatr Hospital, Multan
Rapid Response:
Remdesivir reportedly flopped in Chinese COVID-19 study - yet controversial
Dear Editor,
Earlier this month, a study in the New England Journal of Medicine showed early positive results for remdesivir, developed by California-based Gilead Sciences, with 68 percent of patients improving on the drug [1]. However, the study was not an official trial but rather the collation of data from patients who had been given the drug on a “compassionate use” basis — and was not compared to any control arm. In this study of hospitalized adult patients with severe Covid-19 that was terminated prematurely, remdesivir was not associated with clinical or virological benefits. The scientists behind the study and Gilead warned at the time that it was not conclusive.
Remdesivir has flopped in its first randomized clinical trial, disappointing scientists and investors who had high hopes for remdesivir, according to draft documents published accidentally by the World Health Organization and seen by the Financial Times [2].
After Gilead agreed, Chinese doctors launched two formal studies of remdesivir; one in severely ill patients, and another in people with milder disease. Both studies compared the drug to a placebo. But in mid-April, both were suspended when scientists could not enroll the more than 400 patients needed for each trial. The Chinese trial showed remdesivir did not improve patients’ condition or reduces the pathogen’s presence in the bloodstream. Researchers studied 237 patients, giving the drug to 158 and comparing their progress with the remaining 79. The drug also showed significant side effects in some, which meant 18 patients were taken off it.
“Importantly, because this study was terminated early due to low enrolment, it was underpowered to enable statistically meaningful conclusions.”
“As such, the study results are inconclusive, though trends in the data suggest a potential benefit for remdesivir, particularly among patients treated early in the disease.”
The WHO collates current trials for possible Covid-19 interventions on a website titled “landscape analysis of candidate therapeutics for Covid-19.” A previous version of the website, which contained five pages and a column called “outcomes,” is no longer available. The new one only contains four pages and no “outcome” column.
The WHO said the draft document, which is undergoing peer review, was published early in error. “In response to WHO asking for information and studies to be shared early, a draft document was provided by the authors to WHO and inadvertently posted on the website and taken down as soon as the mistake was noticed.”
There are multiple ongoing Phase 3 studies that are designed to provide the additional data needed to determine the potential for remdesivir as a treatment for Covid-19 [3]. These studies will help inform whom to treat, when to treat and how long to treat with remdesivir. The studies are either fully enrolled for the primary analysis or on track to fully enrol in the near future.
A recent US National Institutes of Health animal study also found the drug was effective at treating the disease in monkeys when taken early in its progression [4].
Gilead expects to release preliminary data from a late-stage study of the drug in treating patients with severe cases of COVID-19 by the end of April. Initial data from a National Institutes for Health study and Gilead's study focusing on patients with moderate symptoms of COVID-19 will be announced in May.
References:
1. Grein, J., Ohmagari, N., Shin, D., Diaz, G., Asperges, E., Castagna, A., Feldt, T., Green, G., Green, M.L., Lescure, F.X. and Nicastri, E., 2020. Compassionate use of remdesivir for patients with severe COVID-19. New England Journal of Medicine.
2. Gilead antiviral drug remdesivir flops in first trial. Financial Times, (https://www.ft.com/content/0a4872d1-4cac-4040-846f-ce32daa09d99)
3. https://clinicaltrials.gov/
4. Williamson, B., Feldmann, F., Schwarz, B., Meade-White, K., Porter, D., Schulz, J., van Doremalen, N., Leighton, I., Yinda, C.K., Perez-Perez, L. and Okumura, A., 2020. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. bioRxiv.
Competing interests: No competing interests