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Clinical Trial
. 2023 Aug;111(2):300-310.
doi: 10.1111/ejh.14011. Epub 2023 Jun 15.

Crovalimab treatment in patients with paroxysmal nocturnal haemoglobinuria: Long-term results from the phase I/II COMPOSER trial

Alexander Röth  1 , Satoshi Ichikawa  2 , Yoshikazu Ito  3 , Jin Seok Kim  4 , Zsolt Nagy  5 , Naoshi Obara  6 , Jens Panse  7   8 , Hubert Schrezenmeier  9 , Simona Sica  10 , Juliette Soret  11 , Kensuke Usuki  12 , Sung-Soo Yoon  13 , Nadiesh Balachandran  14 , Muriel Buri  15 , Pontus Lundberg  16 , Himika Patel  17 , Kenji Shinomiya  18 , Alexandre Sostelly  19 , Jun-Ichi Nishimura  20
Affiliations
Clinical Trial

Crovalimab treatment in patients with paroxysmal nocturnal haemoglobinuria: Long-term results from the phase I/II COMPOSER trial

Alexander Röth et al. Eur J Haematol. 2023 Aug.

Abstract

Objectives: This study reports long-term outcomes from the open-label extension (OLE) period of the Phase I/II COMPOSER trial (NCT03157635) that evaluated crovalimab in patients with paroxysmal nocturnal haemoglobinuria, who were treatment-naive or switched from eculizumab at enrolment.

Methods: COMPOSER consists of four sequential parts followed by the OLE. The primary OLE objective was to assess long-term crovalimab safety, with a secondary objective to assess crovalimab pharmacokinetics and pharmacodynamics. Exploratory efficacy endpoints included change in lactate dehydrogenase (LDH), transfusion avoidance, haemoglobin stabilisation and breakthrough haemolysis (BTH).

Results: A total 43 of 44 patients entered the OLE after completing the primary treatment period. Overall, 14 of 44 (32%) experienced treatment-related adverse events. Steady state exposure levels of crovalimab and terminal complement inhibition were maintained over the OLE. During the OLE, mean normalised LDH was generally maintained at ≤1.5× upper limit of normal, transfusion avoidance was achieved in 83%-92% of patients and haemoglobin stabilisation was reached in 79%-88% of patients across each 24-week interval. Five BTH events occurred with none leading to withdrawal.

Conclusions: Over a 3-year median treatment duration, crovalimab was well tolerated and sustained C5 inhibition was achieved. Intravascular haemolysis control, haemoglobin stabilisation and transfusion avoidance were maintained, signifying long-term crovalimab efficacy.

Keywords: bone marrow failure disorders; complement C5; complement inhibitor; eculizumab; paroxysmal nocturnal haemoglobinuria.

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References

REFERENCES

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