Remdesivir (GS-5734) is being developed by Gilead Sciences, an American biopharmaceutical company based in California with a primary therapeutic focus in antiviral medicines.
Remdesivir is an antiviral drug (broad spectrum) under clinical trial investigation for the treatment of COVID-19 (coronavirus disease). Remdesivir gained public attention due to publication of some of its clinical study results globally for the treatment of COVID-19 disease.
Rationale for Remdesivir potential against corona virus:
Remdesivir has demonstrated favourable findings both in in vitro (in laboratory conditions) and in vivo (Pre-clinical animal studies) results showing effective against RNA viruses in several families, including Coronaviridae (such as severe acute respiratory syndrome (SARS)-CoV, Middle East Respiratory Syndrome (MERS)-CoV and strains of bat corona viruses capable of infecting human respiratory epithelial cells. Remdesivir is a adenosine analog which is metabolized into an active nucleoside triphosphate (NTP) by the host. This NTP targets the virus genome replication process by inhibiting the viral RNA synthesis.
Clinical evaluations:
Remdesivir is currently under evaluation for its efficacy and safety in treatment of Corona virus. Currently, 19 clinical trial studies were active for Remdesivir evaluation worldwide against COVID-19. Remdesivir identified as highly effective in stopping the replication mechanism of the coronavirus by acting against coronavirus polymerases a key enzyme of coronavirus as per the study findings from scientists at the University of Alberta
Compassionate Use:
It means the authorized use of un-authorized medicines which are still under clinical investigation, for patients in emergency clinical need to treat a disease or infection, whenever there are no approved effective medicines available in the market.
Since the clinical trail investigations are ongoing, the evident data on efficacy and safety of this medicine can be obtained from patients under compassionate use programme.
In this COVID-19 pandemic situation, many national regulatory bodies have authorized the use of some approved medicines (like Hydroxychloroquine, tocilizumab, etc.,) for unapproved indication (off label use for COVID-19 treatment) and allowed compassionate use of investigational medicines like Remdesivir use.
Remdesivir was initially used on first coronavirus patient in United States (a 35-year-old man) on 19-Jan-2020 (as compassionate use) with other anti-infective medications. No adverse events were reported pertaining to Remdesivir in this patient.
On 03-Apr-2020, European medicines agency (EMA) authorized use of Remdesivir under compassionate use programme for the treatment of adult and paediatric patients from 12 year of age weighing at least 40 kg requiring invasive mechanical ventilation, due to COVID-19 confirmed by polymerase chain reaction (PCR) or who have known contact with a confirmed case of COVID-19, with PCR pending.
EMA released summary of guidelines and recommendations for Remdesivir use under Compassionate programme.
Solidarity clinical trial studies:
World Health Organization (WHO) and other partners launched Solidarity international clinical trials studies to find an effective treatment for COVID-19. In this Solidarity clinical studies, four treatment options would be compared against standard of care to assess their relative effectiveness against COVID-19.
Remdesivir is one of the four treatment options used under Solidarity trails. Other treatment options included Lopinavir/Ritonavir (approved for HIV treatment), Interferon beta-1a (approved for treating multiple sclerosis), Chloroquine and hydroxychloroquine (approved for the treatment of malaria and rheumatology conditions respectively).
Expedited review on Remdesivir data:
On 30-Apr-2020, EMA initiated rolling review (one of the regulatory tools available to the European medicine agency to speed up the assessment of a promising investigational medicine during a public health emergency, such as the ongoing pandemic) of Remdesivir for COVID-19. The decision on this rolling review is based on the preliminary results published from National Institute of Health (NIH) clinical Trial which showed that “Remdesivir accelerates recovery from advanced COVID-19”.
EMA would review the entire accumulated data and emerging data during review period pertaining to Remdesivir effectiveness against COVID-19 and its safety profile.
Emergency Use Authorization (EUA):
On 01-May-2020, United States FDA announced Emergency Use Authorization for Remdesivir for the treatment of suspected or laboratory-confirmed COVID-19 in adults and children hospitalized with severe disease. This authorization was based on the review of findings from an ongoing clinical trial conducted by National Institute of Allergy and Infectious Diseases (NIAID) which is a randomized, double-blinded, placebo-controlled trial for evaluating the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19 (NCT04280705). FDA also reviewed data from an open-label clinical trial study sponsored by Gilead which evaluated different durations of Remdesivir (NCT04292899; a clinical study evaluating the safety and antiviral activity of Remdesivir (GS-5734™) in participants with severe coronavirus disease).
Based on the available scientific evidence, FDA considered that the known and potential benefits of Remdesivir outweigh the known and potential risks of the drug for the treatment of patients hospitalized with severe COVID-19 (Positive benefit-risk profile under authorized conditions).
Remdesivir Drug Safety Profile:
The following safety findings considered expected as there were observed in clinical trial studies and during compassionate use programmes.
- Increase risk in transaminase elevations (Health care professionals are advised to monitor for hepatic health during and after the treatment period)
- Nausea, vomiting, shivering, sweating and hypotension (low blood pressure) during the administration of the drug (Infusion-related reaction).
Remdesivir use is contraindicated in patients with known hypersensitivity to the drug.
Targeted Spontaneous reporting of Remdesivir adverse events:
Remdesivir is still a “drug under investigation”, however, its use is widespread now globally through compassionate use and multiple clinical trial programmes. Even though this investigational drug is showing effectiveness in treatment of COVID-19, establishment of its safety profile in parallel is of paramount for a more real benefit-risk assessment. As of now, only few safety concerns are identified for this drug (described above). To hasten the accumulation of evident safety data for Remdesivir, the adverse experiences or side effects associated with its use should be monitored for each and every treated patient and report the serious adverse events to the respective national regulatory authority through spontaneous reporting systems.
Advice to health care professionals and Public:
In this COVID-19 Pandemic, Health care professionals treating corona positive patients and patients under COVID-19 treatment are advised to voluntarily report adverse events associated with the treatment medications (both approved and unapproved medicines using under compassionate programmes) to their respective national spontaneous adverse drug reaction (ADR) reporting system. (For guidelines and channels of ADR reporting, please refer to the country specific health authority websites).