Remdesivir is not approved by the FDA nor licensed or approved anywhere in the world.
The investigational drug remdesivir demonstrated that a 10-day treatment course achieved similar improvement in the clinical status of patients as a 5-day treatment course (Odds Ratio: 0.75 [95% CI 0.51 — 1.12] on Day 14). Announced today by Gilead Sciences, these topline results were culled from an open-label phase 3 SIMPLE trial evaluating 5-day and 10-day dosing durations of the antiviral in hospitalized patients with severe manifestations of the coronavirus disease 2019 (COVID-19).1
No new safety signals were identified with remdesivir across either treatment group, according to Gilead.1
Remdesivir is not approved by the FDA nor licensed or approved anywhere in the world. The drug has not yet been demonstrated to be safe or effective for the treatment of COVID-19.1,2
However, remdesivir, a nucleotide analog with broad-spectrum antiviral activity, has demonstrated activity against MERS and SARS, indicating that it may have potential activity against COVID-19.2
Due to the COVID-19 pandemic, the FDA designated remdesivir for ‘compassionate use’ in March 2020, allowing patients with serious or life-threatening cases of the virus to have access to the drug.2 Remdesivir has also been granted the investigational antiviral Orphan Drug status by the FDA.3
“Unlike traditional drug development, we are attempting to evaluate an investigational agent alongside an evolving global pandemic. Multiple concurrent studies are helping to inform whether remdesivir is a safe and effective treatment for COVID-19, and how to best utilize the drug,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences, in a prepared statement.1
Initiated by Gilead, the SIMPLE studies are 2 randomized, open-label, multi-center phase 3 clinical trials for remdesivir, in countries with high prevalence of COVID-19 infection.
The first SIMPLE trial is evaluating the safety and efficacy of 5-day and 10-day dosing regimens of remdesivir in hospitalized patients with severe manifestations of COVID-19. The initial phase of the study randomized 397 patients in a 1:1 ratio to receive remdesivir 200 mg on the first day, followed by remdesivir 100 mg each day until day 5 or 10, administered intravenously, in addition to standard of care. An expansion phase of the study was recently added and will enroll an additional 5600 patients, including patients on mechanical ventilation.
The study is being conducted at 180 trial sites around the world, including sites in the United States, China, France, Germany, Hong Kong, Italy, Japan, Korea, the Netherlands, Singapore, Spain, Sweden, Switzerland, Taiwan and the United Kingdom.
A second SIMPLE trial is evaluating the safety and efficacy of 5-day and 10-day dosing durations of remdesivir administered intravenously in patients with moderate manifestations of COVID-19, compared with standard of care. The results from the first 600 patients of this study are expected at the end of May.
In the first study, the time to clinical improvement for 50% of patients was 10 days in the 5-day treatment group, and 11 days in the 10-day treatment group. More than half of patients in both treatment groups were discharged from the hospital by Day 14 (5-day: 60.0%, n=120/200 vs.10-day: 52.3% n=103/197; p=0.14). At Day 14, 64.5% (n=129/200) of patients in the 5-day treatment group and 53.8% (n=106/197) of patients in the 10-day treatment group achieved clinical recovery.1
“These study results complement data from the placebo-controlled study of remdesivir conducted by the National Institute for Allergy and Infectious Diseases [NIAID] and help to determine the optimal duration of treatment with remdesivir. The study demonstrates the potential for some patients to be treated with a 5-day regimen, which could significantly expand the number of patients who could be treated with our current supply of remdesivir. This is particularly important in the setting of a pandemic, to help hospitals and healthcare workers treat more patients in urgent need of care,” Parsey added.1
Secondary objectives of the study included rates of adverse events and additional measures of clinical response in both treatment groups. Patients were required to have evidence of pneumonia and reduced oxygen levels that did not require mechanical ventilation at the time of study entry, according to Gilead.1
Clinical improvement was defined as an improvement of 2 or more points from baseline on a predefined 7-point scale, ranging from hospital discharge to increasing levels of oxygen support to death. Patients achieved clinical recovery if they no longer required oxygen support and medical care, or were discharged from the hospital.1
Clinical outcomes varied by geography. Outside of Italy, the overall mortality rate at Day 14 was 7% (n=23/320) across both treatment groups, with 64% (n=205/320) of patients experiencing clinical improvement at Day 14 and 61% (n=196/320) of patients discharged from the hospital.1
In an exploratory analysis, patients in the study who received remdesivir within 10 days of symptom onset had improved outcomes compared with those treated after more than 10 days of symptoms. Pooling data across treatment arms, by Day 14, 62% of patients treated early were able to be discharged from the hospital, compared with 49% of patients who were treated late.1
Remdesivir was generally well-tolerated in both the 5-day and 10-day treatment groups, according to Gilead. The most common adverse events occurring in more than 10 % of patients in either group were nausea (5-day: 10.0%, n=20/200 vs. 10-day: 8.6%, n=17/197), and acute respiratory failure (5-day: 6.0%, n=12/200 vs. 10-day: 10.7%, n= 21/197). Grade 3 or higher liver enzyme (ALT) elevations occurred in 7.3% (n=28/385) of patients, with 3.0% (n=12/397) of patients discontinuing remdesivir treatment due to elevated liver tests.1
According to Gilead, NIAID’s study of remdesivir also is showing positive data and has met its’ primary endpoint. That agency will provide more information in an upcoming briefing, according to Gilead.4