SIMPLE study reports benefit from 5-day but not 10-day remdesivir on moderate COVID-19
26 June 2020. Related: COVID-19: investigational drugs, COVID-19.
Simon Collins, HIV i-Base
On 1 June 2020, top-line results were reported in a company press release from the phase 3 SIMPLE remdesivir study.
This study compared 5-day vs 10-day dosing vs standard of care (SoC) in people with moderate COVID-19 pneumonia but without reduced oxygen levels.
The primary endpoint was based on a 7-point scale of clinical symptoms at day 11.
The results reported that 5-day treatment significantly improved outcomes at day 11 compared to the control arm: OR 1.65 (95% CI: 1.09 to 2.48); p=0.017.
Results for the 10-day treatment however were not significantly different from the standard of care arm: OR 1.31 (95% CI: 0.88 to 1.95}; p=0.18.
The most common adverse events occurring in more than 5% of patients in both treatment groups were nausea (10% vs 9% vs 3%), diarrhoea (5% vs 5% vs 7%) and headache (5% vs 5% vs 3%), in 5-day vs 10-day vs SoC, respectively.
Key efficacy and safety results from the press release are included in Table 1.
Table 1: Key efficacy and safety results from SIMPLE study
| 5-Day RDV n=191 |
10-Day RDV n=193 |
SoC n=200 |
|
| Clinical Efficacy Outcomes at Day 11 | |||
| ≥ 2-point improvement in ordinal scale | 134 (70) | 126 (65) | 121 (61) |
| ≥ 1-point improvement in ordinal scale | 146 (76) | 135 (70) | 132 (66) |
| Requiring any oxygen support | 12 (6) | 13 (7) | 22 (11) |
| ≥ 1-point worsening in ordinal scale | 6 (3) | 12 (6) | 22 (11) |
| Death | 0 | 2 (1) | 4 (2) |
| Safety | |||
| Any adverse event (AE) | 97 (51) | 106 (55) | 90 (45) |
| Grade ≥3 AE | 20 (10) | 21 (11) | 24 (12) |
| Any serious adverse event (SAE) | 8 (4) | 7 (4) | 18 (9) |
comment
Even when statistically significant, the summary result in Table 1 do not show especially large differences compared to the SoC inactive control arms. It is also difficult to understand why slightly longer treatment would not replicate the 5-day treatment.
Nevertheless, these results will be used to support 5-day dosing, which will ensure twice as many people are able to access the limited supplies of remdesivir – both in expanded access and when fully available.
Reference
Giiead press statement. Gilead announces results from phase 3 trial of remdesivir in patients with moderate COVID-19. (1 June 2020).
https://www.gilead.com/news-and-press/press-room/press-releases/2020/6/gilead-announces-results-from-phase-3-trial-of-remdesivir-in-patients-with-moderate-covid-19