PiaSky treatment for PNH means fewer blood transfusions: Analysis
Results show approved therapy safely controls red blood cell destruction
Treatment with PiaSky (crovalimab-akkz) controls hemolysis — the destruction of red blood cells in the body — in nearly all people with paroxysmal nocturnal hemoglobinuria (PNH), according to the results of a pooled analysis of published clinical trials.
Further, the data also showed that about two-thirds of individuals given the approved PNH therapy required fewer blood transfusions and saw their levels of hemoglobin, the protein in red blood cells that carries oxygen, stabilize with the drug’s use.
“[PiaSky] showed encouraging efficacy and an acceptable safety profile in patients with PNH, supporting its role as a promising treatment option” for people with the rare acquired disease, the researchers wrote, noting that “the pooled [transfusion avoidance] rate was approximately 65%.”
The findings were detailed in a study titled “Efficacy and Safety of the C5 Inhibitor Crovalimab in Patients With Paroxysmal Nocturnal Hemoglobinuria: A Systematic Review and Meta-Analysis,” published in the European Journal of Haematology.
In PNH, the abnormal activation of the body’s complement cascade, a part of the immune system, leads to the destruction of blood cells, particularly red blood cells. This ultimately results in disease symptoms, often occurring in sudden attacks.
The primary treatment for PNH is medication to block abnormal complement activation, typically by targeting the complement protein C5. Available medications, in addition to PiaSky, are Soliris (eculizumab) and Ultomiris (ravulizumab).
Researchers examined data from 4 studies of PiaSy
In this analysis, researchers based in Brazil sought to provide an overview of the safety and efficacy of PiaSky. To that end, the team pooled results from four published clinical trials involving a total of 275 patients with PNH, which had been conducted across multiple international centers.
Two Phase 3 studies, COMMODORE 2 (NCT04434092) and COMMODORE 3 (NCT04654468), had enrolled patients who had never been treated with complement inhibitors. The other two studies enrolled individuals with PNH who had previously received a C5 inhibitor: the Phase 3 COMMODORE 1 trial (NCT04432584) and Phase 1/2 COMPOSER trial (NCT03157635). All studies reported similar goals and had follow-up periods of about six months.
The analysis noted moderate variation across the studies, but overall, found that approximately two-thirds of PNH patients treated with PiaSky avoided blood transfusions. This variability was eliminated after researchers excluded COMMODORE 3, with efficacy increasing to 68%.
According to the team, their results “[suggest] that COMMODORE 3 contributed to between-study variation and supports the consistency of the remaining studies, which showed more robust agreement.”
Most PiaSky-treated patients (83.5%) achieved hemolysis control, defined as a reduction in levels of LDH, or lactate dehydrogenase, a marker of red blood cell destruction. Levels of LDH dropped to below 1.5 times the upper limit of normal, the data showed. The researchers noted that, when studies were excluded from the analysis one at a time, the medication’s effectiveness ranged from 79% to 85%. The variability across studies was eliminated by excluding COMMODORE 1.
More than 6 of every 10 PNH patients (61.7%) treated with PiaSky showed stabilization of their hemoglobin levels. Even so, there was high variability in outcomes when all four studies were pooled, “suggesting that there may be benefits, but they may vary according to the research or the characteristics of the evaluated population,” the team noted.
When the team compared PiaSky with Soliris, no significant differences were found between the therapies in terms of hemolysis control and hemoglobin stabilization.
Serious adverse events seen in about 15% of patients, but with variability
Regarding safety, the pooled rate of serious adverse events was 14.4%, with statistically significant variability between studies. The incidence of treatment-related adverse events, regardless of severity, was approximately 47%, the data showed.
Most of the events were infections, including pneumonia, upper respiratory tract infections, and skin infections (erysipelas). When the team excluded COMPOSER, the pooled rate of serious adverse events was reduced to 10.1%, with no significant variability.
As many as one-fifth of the patients (15%-20%) participating in COMMODORE 1 developed transient immune complex reactions (TICRs), a type of inflammatory reaction. This was seen particularly among those who switched from Soliris to PiaSky.
Meanwhile, a separate analysis of COMMODORE 1 and COMMODORE 2 data revealed TICRs among those who switched from Soliris or Ultomiris to PiaSky. Here, when COMMODORE 1 and 2 data were pooled, the TICR rate was 11.61%, with low variability.
Over 80% of the patients treated with [PiaSky] reached hemolysis [red blood cell destruction] control. … These findings reinforce [PiaSky’s] potential as a viable therapeutic option in PNH.
Lastly, fewer than 2 of every 100 treated patients required a dose modification, “indicating that most of the patients tolerated the treatment with [PiaSky] without adjustment,” the team wrote. One patient in one study discontinued PiaSky.
Overall, according to the team, “these findings reinforce [PiaSky’s] potential as a viable therapeutic option in PNH.” The researchers wrote that “over 80% of the patients treated with [PiaSky] reached hemolysis control, measured by a decrease in LDH.”
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