Medical breakthroughs that have the power to change the established order are rare. However, such an event has just occurred for patients with hemophilia B. An international team of researchers from the US, Italy, Germany, and the Netherlands has completed a five-year follow-up of participants in the third phase of clinical trials of an innovative gene therapy. The results are so remarkable that they’re being discussed not only in scientific circles, but also among practicing physicians in Spain.
The essence of the experiment was a one-time administration of a drug designed to replace regular injections of clotting factor. Over five years of follow-up, most patients maintained stable levels of the required protein, and bleeding episodes were reduced by more than half. For many, this was a real breakthrough, as hemophilia B treatment has always demanded constant monitoring and frequent doctor visits—until now.
The trial and its participants
The study involved 54 men with an average age just over 41. Almost all suffered from the severe form of the disease, in which factor IX levels in the blood are critically low. Prior to starting therapy, patients underwent a six-month course of standard preventive treatment, after which they received a new gene therapy drug—etranacogene dezaparvovec.
This medication is a genetically modified version of factor IX, delivered to cells using a viral vector. The dosage was calculated individually based on body weight. One participant received a significantly lower dose due to an acute infusion reaction, but most underwent the procedure without complications.
Long-term results
Fifty participants completed the five-year observation period. During this time, two died from causes unrelated to the treatment, one received a liver transplant, and another chose to withdraw from the study. Interestingly, a significant number of patients were found to have viral hepatitis, and some had antibodies to the viral vector, but this had virtually no impact on the therapy’s effectiveness.
The frequency of bleeding episodes in participants dropped by 63 percent compared to the period before receiving treatment. The number of joint bleeds decreased especially significantly—by 85 percent. The average factor IX level in the blood remained stable throughout the follow-up period, and the need for additional injections almost disappeared.
Safety and tolerability
Throughout all five years, no serious side effects associated with gene therapy were recorded. Even the presence of neutralizing antibodies to the viral vector did not reduce the effectiveness of the treatment. This finding came as a surprise to many experts, since it had previously been believed that the immune response could significantly limit the effectiveness of such approaches.
The need for exogenous factor IX to prevent and control bleeding dropped by almost 96 percent. Previously, patients required hundreds of thousands of international units of the drug each year, but now this figure has fallen to minimal levels. For people with hemophilia B, this means not only an improved quality of life but also a reduced financial burden on the healthcare system.
Context and outlook
Hemophilia B is a rare hereditary disorder in which the blood clotting process is impaired. In Spain, as in many other countries, patients with this diagnosis face the need for regular injections and a constant risk of bleeding. The advent of gene therapy has been a real breakthrough, allowing many to leave behind previous limitations.
Since 2022, several gene therapy drugs for treating hemophilia B and A have become available on the market. All of them were approved through an accelerated process, but long-term outcomes remained unknown. Now, with five-year data published, it is clear: the new approach truly works and could soon become the standard treatment.
International experience
Similar studies were previously conducted in the United States, the United Kingdom, and South Africa. There, patients were monitored for more than ten years, and the effects of gene therapy persisted throughout this period. In Spain, doctors are closely following these results, discussing the possibility of introducing new methods into the national healthcare system.
Despite these advances, experts emphasize that further research is needed to assess the long-term safety and effectiveness of the therapy for different patient groups. However, it is already apparent that gene therapy is opening new horizons for people with hemophilia B, enabling them to live full lives without constant medical interventions.
In case you didn’t know, uniQure, the company behind etranacogene dezaparvovec, specializes in developing gene therapies for rare diseases. In partnership with CSL Behring, they have brought several innovative drugs to market that have already transformed hemophilia treatment. Their developments are being actively adopted in clinical practice worldwide, including in Spain, where interest in new therapeutic approaches continues to grow.
