Tocilizumab fails to meet clinical endpoints in randomised COVACTA study: other studies continue
14 October 2020. Related: COVID-19: investigational drugs, COVID-19.
Simon Collins, HIV i-Base
On 1 September 2020, results from the randomised phase 3 placebo-controlled COVACTA trial were published ahead of peer review, showing no clinical benefit of tocilizumab infusion in adults hospitalised with COVID-19. [1}
Top-line results from this study had already been released in a press release from Roche. [2]
The COVACTA study randomised 452 adults with 438 receiving either tocilizumab (n = 294; 8 mg/kg infusion, maximum 800 mg) vs placebo (n=144) in the modified ITT analysis.
Baseline characteristics were balanced and included approximately 70% men; 60% were white and 14% were black and mean age was about 61 (+/– 14) years.
There was no significant difference in primary endpoint of clinical status at day 28 based on a 7-category ordinal scale in tocilizumab vs placebo groups with odds ratio: 1.19 (95%CI: 0.81 to 1.76), p=0.36.
There was also no significant differences in mortality at day 28: 19.7% vs 19.4% in active vs placebo groups respectively: difference 0.3% (95%CI: –7.6% to +8.2%), p=0.9410.
Time to discharge from hospital was shorter with tocilizumab: median 20 (95%CI: 17 to 27) vs 28 days (95%CI: 20 to NE), p=0.037 but this was not significant due to missing the primary endpoint. Median time in ICU was 5.8 days shorter with tocilizumab (9.8 vs 15.50, nominal p=0.045.
There were no significant important safety results between the two groups.
comment
This is disappointing news as several earlier studies reported positive results. [3, 4, 5]
However, as with many of the dozens of tocilizumab studies currently online ahead of peer review, also mainly reporting positive results for COVID-19, these are generally small, retrospective and often use historical controls.
Other phase 3 studies are still ongoing, including the REMDACTA and EMPACTA trials, and several run by independent investigators, potentially to look at shorter hospital and ICU admissions. Although the CONVICTA study reported no benefit, CORIMUNO-TOCI reported reduced mortality or need for oxygen at day 14 and EMPACTA has reported both reduced mortality and need for intubation.
A recent meta-analyses also supported efficacy, though this might only be in a subset of patients, perhaps before the increase in proinflammatory proteins. [6]
On 27 August 2020, the NIH Panel recommended against the use of anti-IL-6 receptor monoclonal antibodies (e.g., sarilumab, tocilizumab) or an anti-IL-6 monoclonal antibody (siltuximab) for the treatment of COVID-19, except in a clinical trial. [7]
The tocilizumab arm of the UK RECOVERY study is apparently still ongoing. [8]
References
- Rosas I et al. Tocilizumab in hospitalized patients with COVID-19 pneumonia. DOI: 10.1101/2020.08.27.20183442. MedRxiv, ahead of peer-review. (1 September 2020).
https://www.medrxiv.org/content/10.1101/2020.08.27.20183442v1 - Roche press release. Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 associated pneumonia. (29 July 2020).
https://www.roche.com/investors/updates/inv-update-2020-07-29.htm - Tocilizumab associated with better outcomes from COVID-19 in US study. HTB (28 August 2020).
https://i-base.info/htb/38827 - Further positive reports from tocilizumab to treat COVID-19. HTB (22 July 2020).
https://i-base.info/htb/38523 - Potential for tocilizumab to treat moderate to severe COVID-19. HTB (14 May 2020). https://i-base.info/htb/37877
- Malgie J et al. Decreased mortality in COVID-19 patients treated with Tocilizumab: a rapid systematic review and meta-analysis of observational studies. CID, ciaa1445. DOI: 10.1093/cid/ciaa1445.
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1445/5910379 - US NIH guidelines panel on management of COVD-19. What’s new in the guidelines (27 August 2020).
https://www.covid19treatmentguidelines.nih.gov/whats-new - RECOVERY study.
http://www.recoverytrial.net
This report was first published on 9 September 2020.