Brii Biosciences could soon become the latest company to get a Covid-19 antibody to market, following positive results from the NIAID-sponsored Activ-2 trial in outpatients. The data show the group’s BRII-196/BRII-198 combo looking similar to the other antibodies that have yielded results so far, on a cross-trial basis at least.
The question now is whether there is room for yet another antibody. Of the main contenders, sales of Lilly’s bamlanivimab plus etesevimab have disappointed, and Regeneron’s casirivimab plus imdevimab has this smaller-than-expected market sewn up, the numbers suggest.
Still, this has not stopped others from trying to get in on the act, with Glaxosmithkline and Vir’s sotrovimab gaining emergency use authorisation in May.
And yet another contender could soon be coming. Data are due this half with Astrazeneca’s AZD7442 from the Tackle trial in the outpatient setting. The future of the long-acting, intramuscularly administered antibody doublet looked in doubt last month after it flunked the Storm Chaser study in post-exposure prophylaxis; however, last week Astra reported a benefit in pre-exposure prevention, fuelling hopes of a resurrection.
Concerns about competition did not appear to deter investors in Brii, who sent the Hong Kong-listed group up 9% today.
The Activ-2 study found a 78% reduction in the risk of hospitalisation and death with BRII-196/BRII-198 versus placebo, putting the project in line with other Covid-19 antibodies, albeit with the usual caveats about cross-trial comparisons.
The data released today are an interim analysis of around 69% patients in the BRII-196/BRII-198 arm of Activ-2, where the blind has been broken to analyse the data.
|How the Covid-19 antibodies have performed in non-hospitalised pts|
|Project||Company/ies||Trial||N||Reduction in risk of hospitalisation/death vs placebo||No. of events|
|BRII-196/BRII-198||Brii Biosciences||Activ-2, NCT04518410||837||78%, p<0.00001||12||45|
|Casirivimab + imdevimab||Regeneron/Roche||NCT04425629||1,484*||70%, p=0.0024||7||24|
|Bamlanivimab + etesevimab||Lilly||Blaze-1, NCT04427501||1,035||70%, p= 0.0004||11||36|
|Sotrovimab (VIR-7831)||Glaxosmithkline/Vir||Comet-Ice, NCT04545060||1,057||79%, p<0.001||6||30|
|*1,200mg dose only. Source: company releases.|
There were no drug-related serious adverse events or deaths, and no severe infusion reactions with BRII-196/BRII-198.
One question is how BRII-196/BRII-198 performed against the Covid-19 Delta variant; data on this will be evaluated, Brii said, adding that in vitro results suggested that its doublet retained activity against variants of concern including Delta.
This could be an important consideration for the evolving antibody market. Lilly has already fallen foul of variants, with the US pausing the distribution of bamlanivimab and etesevimab in June after in vitro data suggested that the antibodies were not effective against the Beta and Gamma variants. This issue has not been seen with Regeneron’s casirivimab plus imdevimab.
Lilly has said that its product does have activity against Delta, according to preclinical data, so no doubt it hopes to start selling the antibodies again soon.
However, expectations have come down lately, with the group now expecting 2021 sales of its Covid-19 antibodies to hit $1-1.1 billion, from $1-1.5bn previously.
Regeneron, meanwhile, had a monster second quarter, booking US sales of $2.6bn for casirivimab and imdevimab from a government contract.
Still, a slowdown is coming, with revenues of just $34m expected in the US this quarter as stockpiling comes to an end for now. Leerink analysts expect things to pick up slightly in the fourth quarter, giving total US sales this year of $3bn, but much depends on whether there is another surge in Covid-19 cases.
As for Vir and Glaxo’s sotrovimab, some of the more bullish analysts still see a multi-billion-dollar opportunity, while others are much more cautious.
Brii recently started a phase 2 trial in China, and already has supply agreements in place in the country, so could find a niche for BRII-196/BRII-198 here. But on the world stage it is hard to see any other group catching Regeneron.