A study conducted at the Hemocentro was published in New England Journal of Medicine
Published on March 17th, in New England Journal of Medicine (NEJM), the editorial signed by Courtney D. Thornburg – medical director of the Thrombosis and Hemophilia Center at Rady Children's Hospital in San Diego – presents a study conducted at the Unicamp Blood Center by a professor at the Department of Clinical Medicine (DCM) at the Faculty of Medical Sciences (FCM), Margareth Ozelo. The result is promising: a new gene therapy, called valoctocogene uvaparvovec, emerges as a truly transformative alternative for patients with hemophilia.
“Health systems, public policy makers, insurers, doctors and other representatives of society must begin to prepare the way for this new reality”, says Thornburg in a retrospective of the last 30 years of research involving gene therapy care for people with hemophilia A (factor VIII deficiency) and hemophilia B (factor IX deficiency). The method currently used consists of introducing a normal factor VIII or factor IX gene into a patient's target cell, in this case liver cells, through a modified viral vector, the adeno-associated virus.
In his article, Thornburg explains that the treatment of people with severe hemophilia A (factor VIII < 1%) involves the administration of medications aimed at increasing factor VIII levels and thus preventing or controlling bleeding. Such prophylaxis can be intravenous, with the administration of a clotting factor, or subcutaneously, with the application of the antibody emicizumab. Despite offering a better quality of life to patients, with a reduction in bleeding, both medications are expensive and do not completely prevent new bleeding or chronic arthropathy associated with pain, with a consequent reduction in the patient's mobility.
Thornburg says that the first trial involving gene therapy took place in 1999, in patients with hemophilia B, research with which Professor Margareth Ozelo also collaborated. The first successful case of adeno-associated virus-mediated gene transfer was recorded in 2011 by a group of researchers led by Amit Nathwani of University College London. In the case of hemophilia A, the success of gene therapy was slower, due to challenges involving the size of the factor VIII gene and the difficulty of packaging it into the vector virus. It was necessary to move towards a type of technology that would enable a smaller transgene with greater expression. Gene therapy trials in patients with hemophilia A, using technology AAV5-hFVIII-SQ (valoctocogene Roxaparvove), began in 2015.
It is in this scenario of use of valoctocogene Roxaparvove which is part of the multicenter study led by Margareth Ozelo highlighted in the most recent publication of NEJM. This is the largest gene therapy study for hemophilia A in the world. In total, 134 patients with severe hemophilia A underwent a single dose of valoctocogene uvaparvovec (6x1013 vector genomes per kilogram of weight). After treatment, the vast majority of patients presented factor VIII levels in the mild hemophilia range (5 to < 40%) or in the non-hemophilia range (≥ 40%), with an improvement in the bleeding phenotype.
As the FCM professor explained to the NEJM, additional evaluation is still needed to determine the durability of response to therapy, as well as predictors of response, important considerations for patients when deciding on gene therapy. “Safety is a key consideration in any new therapy and a huge concern for a population devastated by virus-contaminated blood products in the 1980s and early 1990s,” adds Thornburg in his editorial.
In addition to the recently published work, Margareth Ozelo participates in four other gene therapy studies for hemophilia. To date, 34 patients have already received this type of treatment at the Unicamp Blood Center. The HC Blood Center is currently one of the centers with the largest number of patients treated with this type of advanced therapy in the world.
Read the full editorial here.
Read the full scientific article here.
Original article published on the Faculty of Medical Sciences (FCM) website.
