A new study examines and compares re-dosing rates inter alia for human C1 esterase inhibitor in recombinant form (Ruconest®) and plasma-derived forms (Berinert®, Cinryze®) to icatibant (Firazyr®) in seven individual patients at risk of HAE attacks. A total of 69 attacks were recorded. The study was led by Professor Dr Marcus Magerl of the Department of Dermatology and Allergy at the Charité Universitätsmedizin Berlin, Berlin, Germany. The main outcome of the study was that treatment with recombinant therapy Ruconest® and plasma-derived C1 treatments requires significantly less re-dosing than icatibant (Firazyr®) to resolve HAE attacks.
There were 69 initial attacks in total across all seven patients. In this real-world study, the patients were able to choose the treatment for their attack. Following initial intervention, some patients needed to treat their attacks with a second dose or subsequent treatments to try to resolve the attack. The choice of the subsequent re-treatments was also decided by the patient. The majority of the attacks were classified as mild (67%), with 27% moderate and 6% severe.
Patients treated their attack initially with either Berinert® (five attacks) or Cinryze® (17 attacks), both plasma-derived C1 esterase inhibitors (“pdC1INH”), or Firazyr® (25 attacks) (icatibant, a small molecule bradykinin inhibitor, “Icatibant”), or Ruconest® (20 attacks), a recombinant human C1 esterase inhibitor (“rhC1INH”).
In the study, Ruconest® showed 100% efficacy with first dose at appropriate clinical levels. In two cases, additional therapy was applied because of initial underdosing of the first treatment. Cinryze® and Berinert® also showed good results.
The main difference, however, was shown in those patients who selected Firazyr® as their first line therapy. These patients recorded re-dosing rates that were higher than controlled clinical studies have indicated before.
Of the 25 attacks treated with Firazyr® as a first line therapy, 11 (44%) failed on the first dose. In eight of those 11 failed therapy situations (72%), the patient took a second dose of Firazyr® to try to end the attack. In the other three cases, the patients took a C1 esterase inhibitor (two taking Berinert®, and one Ruconest®).
All of the patients who took a C1 esterase inhibitor reported the attack resolved, whereas in a further five of the eight Firazyr® treatments patients had to take a third dose of medication to try to resolve the attack. Where either Ruconest® (two) or Berinert® (one) were used as the third treatment of the attack, it was again resolved, whereas one out of two attacks re-treated with Firazyr® required a fourth dose of Firazyr® for the attack to be resolved.
Further data regarding reasons for drug selection and subjective observations on the performance of the drugs in each attack are being analysed and the full results of the study will be published by the investigators in due course.
Dr Bruno Giannetti, Chief Operations Officer of Pharming Group N.V., said:
“This was a well-run independent investigator-led comparative study under real world conditions, which gives a clear signal confirming reports from patients: Treatment with adequate doses of C1 esterase inhibitor is an excellent therapy to minimize and end an acute HAE attack. It also confirms that re-dosing with icatibant is often needed to successfully treat an attack. In fact, this study reports failure rates for treatment with icatibant of 44% for the first dose and 62% for the second dose, with one of the patients needing to take four doses to stop one attack.”