Long-term effectiveness and safety of ravulizumab in paroxysmal nocturnal hemoglobinuria: a plain language summary

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease where red blood cells break apart because they lack certain protective proteins. This makes them easy targets for the immune system, which can also affect other blood cells. PNH can lead to blood clots and serious organ damage. Ravulizumab and eculizumab block C5, part of the immune system that destroys blood cells in PNH. Ravulizumab is given every 8 weeks, reducing treatment burden compared to eculizumab's 2-week schedule. Ravulizumab was studied in two 26-week trials (301 and 302) for PNH. One compared it to eculizumab in participants new to treatment, and the other looked at switching from eculizumab. Both medicines were equally effective and well-tolerated. This summary covers the extension period - an extra phase after the main study - of studies 301 and 302, to see if ravulizumab stayed safe and effective over up to 2 years. Participants on ravulizumab continued treatment, while those on eculizumab switched to ravulizumab. It also includes an additional analysis from studies 301 and 302 on breakthrough intravascular hemolysis (BTH), where red blood cells can break apart during treatment due to insufficient medication or health issues such as infections.

A total of 434 people continued taking ravulizumab during the extension period. For up to 2 years, 90-95% of participants maintained a low level of LDH, a blood marker of red blood cell breakdown, indicating that PNH was under control. Most participants did not need blood transfusions. The improvement in participants' quality of life lasted over the 2 years. Ravulizumab was well tolerated. In studies 301 and 302, ravulizumab had a lower risk of BTH compared to eculizumab.

This study shows that ravulizumab remains safe and effective for longterm PNH treatment.