aHUS Trials Watch 11 ( Crovalimab)

Article No. 415

1 February 2021

In a recent article (article413) about research into why specifically  monoclonal antibodies (mAb) work when blockading Complement Protein C5 , a novel mAb called crovalimab was mentioned. It is a new mAb developed by the Hoffmann La Roche pharmaceutical company. Although Chugai Pharmaceuticals, a Japanese company,  created it.

Crovalimab is described as a sequential mAb recycling technology for extended self admininistered sub cutaneous doses for C5 inhibition.

Crova is a “li” mAb but not a  “li” zu” mAb ( under new naming conventions “zu” is not needed ) But “li” indicates that it impacts on the immune system as do  eculizumab and Ravulizumab. The prefix “Crova” means nothing  just as  “Ecu” or “Ravu” do ( except perhaps  to the group of people at a meeting who came up with them,  could it just be the first name initials of those attending the meeting?).

The new mAb sticks to a different part of C5 , a different “epitope” as clinicians would say, that eculizumab/Ravulizumab  does. As such it also works for those with the C5 mutation (which is mainly experienced in Japan) that eculizumab cannot.

Phase 1 & 2 Trials have been taking place during 2020 on the safety and dosing efficacy of crovalimab for treating Paroxysmal Nocturnal Haemoglobinuria or PNH. The trialists included healthy volunteers, PNH patients who have not been treated with eculizumab , PNH patients who had received eculizumab.

Reports on the outcomes of those trials were given at ASH 2020. Crovalimab was found to be effective. It achieved complete  and sustained blockade of C5.

Some skin reaction was observed for initial injected doses but disappeared with more experience.

As the crovalimab is more soluble it is administered by subcutaneous injection expected to be at four week intervals.

Two Phase 3 studies are going to take place in 2021 with the aim of completion by 2022.

One ( NCT04654468 ) involve 50 Chinese PNH patients from seven hospital sites. These patients will not have been treated with eculizumab prior to joining the trial.

The second (NCT04432584) will involve 250 PNH patients from 121 hospital sites over 27 countries. Patients will have had eculizumab treatment prior to joining the trial and will be allocated to two groups , one where patients stay on eculizumab and the other where patients  will transition to crovalimab.

More often than not, new trials for Complement  therapies start with those involving PNH patients before moving on to aHUS patients. Maybe Phase 3 aHUS trials will start quicker as a result.

Key to whether crovalimab becomes an alternative to eculizumab depends whether

-it works as well clinically, if not better,

– it is as or even more cost effective and

– patients think the  relative burden of treatment is an improvement.

There is every likelihood that trials on aHUS patients will follow.

By 2025  crovalimab could be an alternative option  to eculizumab/Ravulizumab for aHUS patients.

What would aHUS patients prefer, all other things being equal?

Two , four or eight week treatment intervals

Supported Infusions of long duration or swifter but self administered injections.

All will see things differently due to their personal circumstances and preferences for locus of control.