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EHA 2022 | Subcutaneous ravulizumab trial for paroxysmal nocturnal hemoglobinuria treatment

Mustafa Nuri Yenerel, MD, Istanbul University, Istanbul, Turkey, discusses an ongoing Phase III study investigating the safety and efficacy of subcutaneous ravulizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH). Prof. Yenerel first discusses the methodology used in this study, and then goes on to explain the results obtained, the treatment administration satisfaction, and the safety of this agent. This interview took place at the European Hematology Association (EHA) Congress 2022 held in Vienna, Austria.

Transcript (edited for clarity)

This poster presentation summarizes the first year results of subcutaneous ravulizumab. This study is an ongoing, Phase III, multi-centered randomized clinical trial. The main objective was to evaluate the efficacy, treatment, administration, satisfaction, and safety of ravulizumab. In this trial, we have 128 patients. There are two phases, one randomized treatment phase for 10 weeks and extension phase for 172 weeks...

This poster presentation summarizes the first year results of subcutaneous ravulizumab. This study is an ongoing, Phase III, multi-centered randomized clinical trial. The main objective was to evaluate the efficacy, treatment, administration, satisfaction, and safety of ravulizumab. In this trial, we have 128 patients. There are two phases, one randomized treatment phase for 10 weeks and extension phase for 172 weeks. At day one, all the patients were clinically stable patients, and they had used intravenous eculizumab at least more than three months. After randomization, at day one, all the patients got IV ravulizumab with loading dose and day 15 subcutaneous ravulizumab arm patients got weekly subcutaneous ravulizumab as maintenance dose. And at day 15 in the IV ravulizumab arm, patients got IV ravulizumab maintenance dose, and eight weeks later, they switched to subcutaneous ravulizumab arm. They continued subcutaneous ravulizumab in every week as a maintenance dose.

One of the main objectives was efficacy. So efficacy endpoints included LDH levels, stable LDH levels, breakthrough hemolysis incidents, transfusion avoidance, and hemoglobin stabilization. If we look at LDH levels, they were all stable throughout a year, 351 days, LDH levels were all stable. There were very few breakthrough hemolysis in the study, three events in the subcutaneous arm, two events in IV ravulizumab then subcutaneous arm, and four of them were related with infection. One, we didn’t know the etiology, but neither of them are related to low C5, complement 5, inhibition. So it was important.

Treatment administration satisfaction was the second main objective. This is assessed by the treatment administration satisfaction questionnaire, we call TASQ. We calculated the TASQ score, and this TASQ has been shown to be valid for PNH patients and assesses five domains: physical impact, psychological impact, impact for daily activities, convenience, and satisfaction. If you see the reduction of the TASQ score, it will indicate treatment administration satisfaction. In this trial, we showed a reduction of the TASQ score just after the subcutaneous injection. So all the patients were really satisfied with this root of treatment. So it was good and this is maintained through a year. So it is good for us to see.

Our current objective was safety. Almost all of the patients reported at least one adverse event, but they were all grade one or two. Serious adverse events, or grade four adverse events, were very low. We didn’t see any meningoccal infection or major adverse vascular events through a year in this study. Actually, as a conclusion, subcutaneous ravulizumab is well tolerated, safe. There are some side effects, but they were comparable with IV eculizumab and ravulizumab. So it looks safe. There are some device issues, because during the subcutaneous route, we use on-body delivery system kits loaded with ravulizumab. There are some device problems, but 99.9% of the patients got their ravulizumab.. So it seems safe, and a subcutaneous route is an alternative treatment choice for C5, complement five, inhibitor treatment.

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Disclosures

Alexion.