HTB

DSMB stops REGN-COV2 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 (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]

comment

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.

References

  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).
    https://investor.regeneron.com/news-releases/news-release-details/regn-cov2-independent-data-monitoring-committee-recommends
  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.
    https://newsroom.regeneron.com/news-releases/news-release-details/regenerons-covid-19-outpatient-trial-prospectively-demonstrates
  3. Regeneron’s REGN-COV2 antibody cocktail reduced viral levels and improved symptoms in non-hospitalized COVID-19 patients. (29 September 2020).
    https://investor.regeneron.com/news-releases/news-release-details/regenerons-regn-cov2-antibody-cocktail-reduced-viral-levels-and
  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).
    https://www.recoverytrial.net/news/recovery-covid-19-phase-3-trial-to-evaluate-regeneron2019s-regn-cov2-investigational-antibody-cocktail-in-the-uk
  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.