Ravulizumab proven effective in paroxysmal nocturnal haemoglobinuria

Ravulizumab is a potential treatment for paroxysmal nocturnal haemoglobinuria (PNH), with an efficacy and safety profile that persists over 52 weeks of follow-up, according to a new study presented at the recently concluded 61st Annual Meeting and Exposition of the American Society of Haematology (ASH 2019).

The present study is an extension of a prior open-label, phase III multicentre study, which randomly assigned PNH patients who were on stable eculizumab treatment for at least 6 months to either “continue treatment as is” (n=98) or “switch to ravulizumab” (n=97). After another 26 weeks, those in the former group were switched to ravulizumab while those in the latter arm received maintenance therapy. Change in lactate dehydrogenase (LDH) from baseline was considered as the primary endpoint.

Four patients dropped out of the study, one of whom belonged to the ravulizumab arm. A total of 191 patients completed the initial treatment and entered the extension period. The final sample size after 52 weeks was 189.

Treatment response, as measured by the change in LDH levels, was durable until week 52 in both treatment arms. By study end, patients who received ravulizumab for the entire duration of the trial showed an 8.8-percent increase in LDH from baseline; those who were switched into the test medication had a 5.8-percent increase. [ASH 2019, abstract 2231]

Notably, mean LDH concentrations in either group were kept within “1.0 times the upper limit of normal,” or <246 U/L.

“Adult patients with PNH on stable eculizumab therapy who received ravulizumab over 52 weeks experienced durable efficacy,” said researchers. Similarly, those who “received eculizumab for 26 weeks and then switched to ravulizumab had an efficacy response consistent with patients” in the parallel arm.

Few episodes of breakthrough haemolysis were recorded in both treatment arms. Incidence rates remained low over the long-term follow-up. Haemoglobin stabilization likewise remained relatively stable during the extension phase of the trial.

Moreover, transfusions within 1 year before the first treatment dose was reported in 13.4 percent and 12.2 percent of the patients who were on ravulizumab treatment all throughout or those who switched to it, respectively. Rates of transfusion avoidance were stable during the study period.

Aside from its efficacy, “ravulizumab continued to be well tolerated through week 52 with no new safety concerns,” the researchers pointed out.

During the extension phase of the trial, fatigue was the most commonly recorded side effect, occurring in 13.5 percent of patients who had received only ravulizumab and in 13.7 percent of those who were initially treated with eculizumab. In the latter treatment arm, headaches were also common, with a prevalence rate of 10.5 percent.

No new treatment-emergent, antibody-positive responses were reported during the extension phase, nor any records of deaths, meningococcal infections or discontinuations due to side effects.