Topline results were announced by Gilead from the first open-label, phase 3 SIMPLE trial evaluating remdesivir, an investigational nucleotide analog with broad spectrum antiviral activity, in hospitalized patients with severe coronavirus disease 2019 (COVID-19).
In the study, patients (N=397) were randomized to receive remdesivir 200mg on the first day, followed by 100mg each day until day 5 or 10, in addition to standard of care. The trial demonstrated that patients who received 10 days of treatment (n=197) achieved similar improvement in clinical status as those who received a 5-day course (n=200) (odds ratio 0.75 [95% CI, 0.51-1.12] on Day 14).
On Day 14, 64.5% of patients in the 5-day group and 53.8% of those in the 10-day group achieved clinical recovery. Moreover, 60.0% of patients in the 5-day group and 52.3% of patients in the 10-day group were discharged from the hospital by Day 14.
“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,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences.
The study also revealed that early treatment may have an impact on outcomes. Compared with those treated after more than 10 days of symptoms, patients who received remdesivir within 10 days of symptom onset were found to have improved outcomes, with a greater proportion of patients discharged from the hospital by Day 14 (62% with early treatment vs 49% with late treatment).
As for safety, the most common adverse events (occurring in >10% of patients) included nausea and acute respiratory failure; 7.3% of patients experienced grade 3 or higher liver enzyme elevations. Treatment was found to be generally well tolerated in both groups.
“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,” added Parsey.
According to preliminary results from the NIAID study, hospitalized patients with advanced COVID-19 treated with remdesivir were found to recover 31% faster than those who received placebo. Specifically, the data showed a median recovery time of 11 days for remdesivir-treated patients vs 15 days for those who received placebo (P <.001). Moreover, the mortality rate in the remdesivir arm was observed to be 8.0% vs 11.6% in the placebo group (P =.059), suggesting a survival benefit with treatment.
In a press briefing, NIAID Director and White House health advisor Dr Anthony Fauci compared the positive results of this highly powered, placebo-controlled trial to the discovery of the first HIV drug over 30 years ago. “This will be the standard of care,” said Fauci.
Among the positive news, results from a randomized, double-blind, placebo-controlled study published in The Lancet showed that remdesivir was not associated with statistically significant clinical benefits in patients with severe COVID-19 (hazard ratio 1.23 [95% CI, 0.87-1.75]). The study, which included 237 critically ill patients in China, investigated a similar 10-day course of treatment. The study was stopped early due to low enrollment and as such, statistically meaningful conclusions on the effectiveness of the drug could not be made.
“Unfortunately, our trial found that while safe and adequately tolerated, remdesivir did not provide significant benefits over placebo,” said lead investigator Professor Bin Cao from China-Japan Friendship Hospital and Capital Medical University in China. “This is not the outcome we hoped for, but we are mindful that we were only able to enroll 237 of the target 453 patients because the COVID-19 outbreak was brought under control in Wuhan. What’s more, restrictions on bed availability resulted in most patients being enrolled later in the disease course, so we were unable to adequately assess whether earlier treatment with remdesivir might have provided clinical benefit.”
While not statistically significant, the trial did show that patients treated with remdesivir within 10 days of symptom onset had a numerically faster time to clinical improvement than those who received placebo (median 18 days vs 23 days, respectively). Moreover, the duration of invasive mechanical ventilation was observed to be shorter in the remdesivir arm compared with the placebo group (median 7 days vs 15.5 days, respectively).
The safety and efficacy of remdesivir for the treatment of COVID-19 are being evaluated in multiple ongoing phase 3 clinical trials. Results from a study evaluating a 5-day and 10-day regimen of remdesivir in the first 600 patients with moderate disease are expected at the end of May.
For more information visit gilead.com.