A second prophylaxis win for Covid-19 antibodies

Like Lilly, Regeneron reckons its antibodies can be used to prevent Covid-19 infection. Now comes the hard part.

Trial Results

Regeneron has matched Lilly in showing that it has a viable approach to preventing Covid-19 infection with an antibody. Both companies’ MAbs carry US emergency use authorisation as Covid-19 treatments, and clinical data suggest that they could soon become available in the prophylactic setting too.

The focus will now turn to logistics. Unless such antibodies are made significantly more convenient and quicker to administer at home the positive results might not count for much, and the respective treatments risk going down as little more than scientific curiosities.

The data Regeneron released today relate to an interim analysis of Study 2069, testing casirivimab plus imdevimab versus placebo in households where one or more individuals is infected with Covid-19. This is subtly different from Lilly’s reported passive immunisation data on bamlanivimab in Blaze-2, a trial in nursing homes.

Bamlanivimab is given via a 60-minute IV infusion, while the Regeneron combo was given as a subcutaneous injection said to be “more convenient and efficient for patients and overburdened healthcare providers and facilities”. Just how convenient this kind of drug must be to allow widespread outpatient use is the big question.

Impressive results

The data, however, are impressive. Regeneron says the first 409 subjects randomised into Study 2069 showed a 50% reduction in confirmed Covid-19 infections, the trial’s co-primary endpoint. Specifically, there were 23 infections among the 223 placebo recipients versus just 10 in the 186 given Regeneron’s combo of casirivimab plus imdevimab.

The company offered no statistical analyses, but noted that the trial has enrolled over 2,000 patients, and according to clinicaltrials.gov it has a recruitment target of 2,450. However, even if the numbers are still too small to yield statistical significance, the numerical benefit is clear.

Further analyses, most strikingly concerning symptomatic infections, paint an even more positive picture. None of the actively treated patients developed symptomatic Covid-19, Regeneron said, while eight of the 23 infections in placebo recipients were symptomatic.

Moreover, in the treated group the infections showed a shorter average duration of viral shedding (nine versus 44 weeks), and infected placebo recipients showed peak viral loads more than 100-fold higher than those infected in the active cohort.

There was also a reduction in infection duration – three to four weeks for placebo, versus a week or less for casirivimab plus imdevimab. Again there were no statistics provided, and some will criticise Regeneron for cherrypicking data, but merely reducing Covid-19 severity is still seen as a real benefit.

For its part Lilly last week said bamlanivimab cut risk of developing symptomatic Covid-19 by 57% versus placebo among nursing home residents and staff, and by 80% among residents (Lilly Blazes a trail in Covid-19 prevention, January 21, 2021). Unlike Regeneron the company provided no absolute infection numbers, but did cite odds ratios and p values, which were highly positive.

Selected prevention studies with Covid-19 antibodies
Project Dosing Company Trial Setting Data?
Bamlanivimab (LY-CoV555)* IV Lilly/Abcellera Blaze-2 Prevention in nursing home residents and staff Odds ratio for infection 0.43 (p=0.00021) for treatment vs placebo in all 965 initially Covid-19 -ve subjects; 0.20 (p=0.00026) among 299 -ve residents
Casirivimab + imdevimab (REGN-COV2) SC Regeneron Study 2069 Prevention in household contacts of Covid-19 patients 10/186 treated subjects infected (0 symptomatic) vs 23/223 infections (8 symptomatic) for placebo
AZD7442 IM Astrazeneca Provent "Pre-exposure prophylaxis" Due H1 2021
IM Storm Chaser "Post-exposure prophylaxis"
*Trial also includes combo with LY-CoV016 in treatment. Source: clinicaltrials.gov & EvaluatePharma.

Lilly and Regeneron both say they want to discuss the prevention data with regulators with a view to broadening their MAbs’ EUAs.

If Regeneron’s combo has a convenience advantage over Lilly’s MAb then it shares this with a third competitor, Astrazeneca. The UK group has not yet reported prevention data with AZD7442, a MAb dosed intramuscularly.

The stage is now set for dosing convenience and logistics to be an increasingly important consideration as companies try to get these types of passively immunising antibodies into domestic settings at scale. The risk is that there will be no contest against the more typical vaccination already being rolled out globally.

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