Studies point out new milestones in Hemophilia treatment

USA: Two important studies published in the Lancet Haematology and the New England Journal of Medicine have shed light on the new milestones for haemophilia treatment.

Haemophilia A is the most common severe form of haemophilia. It affects almost exclusively the male sex. The disease can usually be treated well, but the medicines known so far do not help all those affected.

Patients with haemophilia A lack coagulation factor VIII which needs to be substituted so that the blood clots and the patients do not bleed. In a clinical phase 3 trial with the participation of the Haemophilia Centre of the University Hospital Bonn (UKB), a new drug with the complicated name, Efanesoctocog Alpha, has now been investigated for the treatment of haemophilia A for the first time. The new findings represent a milestone in haemophilia treatment and have now been published in the renowned New England Journal of Medicine.

Efanesoctocog Alpha is the first drug to contain a genetically engineered clotting factor VIII, with a significantly prolonged action duration of 47 hours. The study with 133 patients shows that blood clotting with the new drug is almost normalised over four days and provides good protection against bleeding over seven days. The number of bleedings is reduced from three bleedings in 12 months with the classical treatment to only one bleeding in 18 months with Efanesoctocog Alpha. The long duration of action is achieved by a series of genetic modifications of the factor VIII protein, the most important of which is blocking the binding to the Von Willebrand factor, which otherwise determines the speed of factor VIII clearance.

In parallel, a study on the prophylaxis of less severe forms of haemophilia A with the monoclonal antibody emicizumab was published in Lancet Haematology. These patients have comparatively little bleeding so the classic bleeding-preventive therapy with multiple intravenous coagulation factor VIII administrations per week does not seem feasible for many patients. Nevertheless, most adult patients show significant bleeding sequelae, especially in the joints. Until now, emicizumab was only approved for treating patients with severe haemophilia A. The current study shows very good results, including a very good efficacy in patients with a less severe form of haemophilia A. Thus, the patients treated with emicizumab, given subcutaneously only once every one to two weeks, had on average less than one bleeding episode per year. As with the earlier approval studies on emicizumab, the haemophilia centre of the UKB was also significantly involved in this study. Almost simultaneously with the publication, the approval of emicizumab for haemophilia A patients with a moderately severe course was granted.

Prof. Johannes Oldenburg, Director of the Institute for Experimental Haematology and Transfusion Medicine at the UKB, which also includes the Haemophilia Centre, states: "Efanesoctocog alpha with its prolonged duration of action and emicizumab for patients with a moderate course of the disease represent important milestones in the treatment of haemophilia A patients. This prevents bleeding and its consequences, especially joint damage and severe pain, so patients with haemophilia A continue to have a good quality of life in adulthood."

The Haemophilia Centre at the University Hospital Bonn (UKB) is one of the largest centres in Europe. About 15 percent of haemophilia patients in Germany are treated here.

References:

1. Von Drygalski A, Chowdary P, Kulkarni R, Susen S, Konkle BA, Oldenburg J, Matino D, Klamroth R, Weyand AC, Jimenez-Yuste V, Nogami K, Poloskey S, Winding B, Willemze A, Knobe K; XTEND-1 Trial Group. Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A. N Engl J Med. 2023 Jan 26;388(4):310-318. doi: https://www.nejm.org/doi/10.1056/NEJMoa2209226

2. Négrier C, Mahlangu J, Lehle M, Chowdary P, Catalani O, Bernardi RJ, Jiménez-Yuste V, Beckermann BM, Schmitt C, Ventriglia G, Windyga J, d'Oiron R, Moorehead P, Koparkar S, Teodoro V, Shapiro AD, Oldenburg J, Hermans C. Emicizumab in people with moderate or mild haemophilia A (HAVEN 6): a multicentre, open-label, single-arm, phase 3 study. Lancet Haematol. 2023 Jan 27:S2352-3026(22)00377-5. doi: https://doi.org/10.1016/S2352-3026(22)00377-5