ESPN 54th Annual Meeting

ESPN 2022


 
TWO PHASE III TRIALS EVALUATING CROVALIMAB IN PATIENTS WITH ATYPICAL HAEMOLYTIC UREMIC SYNDROME (AHUS): COMMUTE-A AND COMMUTE-P
NEIL SHEERIN 1 LARRY A. GREENBAUM 2 SHUICHI ITO 3 CHANTAL LOIRAT 4 SHOICHI MARUYAMA 5 MING-HUI ZHAO 6 KHALED BENKALI 7 CHRISTELLE PIETERSE 8 MONA D. SHAH 9 ALEXANDRE SOSTELLY 8 SASHA SRECKOVIC 8 FADI FAKHOURI 10

1- TRANSLATIONAL AND CLINICAL RESEARCH INSTITUTE, NEWCASTLE UNIVERSITY, NEWCASTLE UPON TYNE, UNITED KINGDOM
2- EMORY UNIVERSITY AND CHILDREN’S HEALTHCARE OF ATLANTA, ATLANTA, GEORGIA, USA
3- DEPARTMENT OF PAEDIATRICS, GRADUATE SCHOOL OF MEDICINE, YOKOHAMA CITY UNIVERSITY, YOKOHAMA, JAPAN
4- UNIVERSITY HOSPITAL ROBERT DEBRÉ, PARIS, FRANCE
5- NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE, NAGOYA, JAPAN
6- PEKING UNIVERSITY FIRST HOSPITAL, BEIJING, CHINA
7- CERTARA, INC., PARIS, FRANCE
8- F. HOFFMANN-LA ROCHE LTD, BASEL, SWITZERLAND
9- GENENTECH, INC., SOUTH SAN FRANCISCO, CALIFORNIA, USA
10- VAUDOIS UNIVERSITY HOSPITAL CENTER (CHUV), LAUSANNE, SWITZERLAND
 
Introduction:

aHUS is a life-threatening disease of complement dysregulation, characterised by thrombotic microangiopathy (TMA). While treatment with C5 inhibition is effective, currently approved therapies require regular intravenous infusions. Crovalimab, a novel anti-C5 monoclonal antibody, allows for small-volume, subcutaneous self-injections. Crovalimab is being tested for treatment of aHUS in two global, Phase III single-arm trials: COMMUTE-a and COMMUTE-p.

Material and methods:

 

COMMUTE-a (NCT04861259) will enrol 3 cohorts of patients with aHUS aged ≥ 12 years and weighing ≥ 40 kg (N ≈ 90): 1) Naive (n ≈ 60): complement inhibitor-naive patients; 2) Switch (n ≈ 30): patients switching from eculizumab/ravulizumab; and 3) C5 SNP (n < 5): patients with a known single-nucleotide polymorphism (SNP).

COMMUTE-p (NCT04958265) will enrol 3 cohorts of patients with aHUS aged ≥ 28 days to < 18 years and weighing ≥ 5 kg (N ≈ 35): 1) Naive (n ≈ 20): complement inhibitor-naive patients; 2) Switch (n ≈ 10): patients switching from eculizumab/ravulizumab; and 3) Pretreated (n < 10): patients who received and discontinued prior eculizumab/ravulizumab treatment.

In both COMMUTE-a and COMMUTE-p trials, patients will receive weight-based crovalimab as a weekly loading series (Weeks 1-4; intravenous dose on Day 1, followed by subcutaneous dosing for subsequent loading doses), followed by self-administered, subcutaneous maintenance doses once every 4 weeks (or once every 2 weeks if < 20 kg; Week 5 onward). The primary objective for both studies is to evaluate the efficacy of crovalimab in Naive patients, based on the proportion of patients with complete TMA response any time from baseline to Week 25.

 

Results:

COMMUTE-a and COMMUTE-p are currently enrolling.

Conclusions:

Both COMMUTE-a and COMMUTE-p will assess the efficacy and safety of crovalimab in patients with aHUS.