DSMB stops REGN-COV2 (casirivimab/imdevimab) monoclonal antibody study in people with high-flow oxygen or ventilation: implications for UK RECOVERY study

Simon Collins, HIV i-Base

On 30 October 2020, the DSMB for a study of REGN-COV2 (casirivimab/imdevimab – a combination of two monoclonal antibodies against COVID-19), recommended stopping use in participants needing high-flow oxygen or ventilation due to a potential safety signal and an unfavourable risk/benefit profile in this group. [1]

The trial is designed to enrol patients in four independently randomised cohorts:

  • Cohort 1: patients on low-flow oxygen 
  • Cohort 1A: patients not requiring oxygen
  • Cohort 2: patients on high-flow oxygen
  • Cohort 3: patients on mechanical ventilation

Continued enrolment is allowed in participants in earlier infection, and in a separate outpatient study.

This notice came only two days after a press release from the manufacturer reporting a second set of positive results from a phase 2/3 study. [2]

This reported both reductions in viral load and hospital visits in 524 participants with mild to moderate COVID-19 randomised to active treatment or placebo, both with standard of care.

Participants were prospectively categorised by whether or not they had already generated an antibody response to COVID-19 (38% positive, 51% negative and 11% unclear/unknown).

The results are similar to earlier results on an initial 275 participants released by press statement last month. [3]

The new results (n=524) included:

  • Mean change from baseline in viral load was 0.68 log10copies/mL lower at day 7 reduction with REGN-COV2 vs placebo (combined dose groups; p<0.0001).
  • A 1.08 log greater reduction with REGN-COV2 vs placebo by day 5.
  • In the overall patient group with detectable virus at baseline, the average daily reduction in viral load through day 7 was a 0.36 log10 copies/mL greater reduction with REGN-COV2 compared to placebo (combined dose groups; p=0.0003).
  • Higher baseline viral load and/or no detectable antibodies at baseline was associated with greater benefit from REGN-COV2.

The results in the total analysis (n=799) included:

  • On a primary clinical endpoint, REGN-COV2 reduced COVID-19 related medical visits by 57% through day 29 (2.8% combined dose groups; 6.5% placebo; p=0.024). 
  • Treatment with REGN-COV2 reduced COVID-19 related medical visits by 72% in patients with one or more risk factor (including being over 50 years of age; body mass index greater than 30; cardiovascular, metabolic, lung, liver or kidney disease; or immunocompromised status) (combined dose groups; nominal p=0.0065).

The results have been reported to the US FDA and will be compiled and submitted for publication.

REGN-COV2 is being developed in the US by Regeneron Pharmaceuticals and is currently in studies for hospitalised and non-hospitalised COVID-19 and as prophylactic prevention.

REGN-COV2 was also recently added as a new option in the UK RECOVERY study. [4]

In August, Regeneron partnered with Roche Pharmaceuticals to increase production of REGN-COV2. [5]


Further clinical details about the DSMB decision were not included in the press release.

Although the virological results hint at a positive effect of the dual antibodies, any publication in a company press release needs to interpreted with caution. Without more details it is difficult to comment further.


  1. REGN-COV2 independent data monitoring committee recommends holding enrollment in hospitalized patients with high oxygen requirements and continuing enrollment in patients with low or no oxygen requirements. (30 October 2020).
  2. Regeneron’s covid-19 outpatient trial prospectively demonstrates that REGN-COV2 antibody cocktail significantly reduced virus levels and need for further medical attention. (29 October 2020.
  3. Regeneron’s REGN-COV2 antibody cocktail reduced viral levels and improved symptoms in non-hospitalized COVID-19 patients. (29 September 2020).
  4. The RECOVERY study. RECOVERY COVID-19 phase 3 trial to evaluate Regeneron’s REGN-COV2 investigational antibody cocktail in the UK. (14 September 2020).
  5. Roche press release. Roche and Regeneron collaborate to significantly increase global supply of REGN-COV2 investigational antibody combination for COVID-19. (19 August 2020).

This report was first posted on 30 October 2020.

Links to other websites are current at date of posting but not maintained.