Preventive Advate Found Better Than On-demand Treatment in Hemophilia A

When given as a prophylactic, or preventive therapy, Advate worked better than on-demand treatment at lowering the number of spontaneous bleeds in people with moderate or severe hemophilia A, according to seven-year data from a real-world study.

A separate analysis of the study, called AHEAD International (NCT02078427), also demonstrated that prophylactic Advate was superior to on-demand treatment at lowering the number of joint bleeds.

These findings are part of a set of 14 electronic posters that Takeda, the therapy’s developer, recently presented at the Virtual European Association for Haemophilia and Allied Disorders Congress (EAHAD). This year, the 14th annual conference was held online.

According to Takeda, these data reinforce the long-term safety and efficacy of several of its hemophilia therapies in routine clinical practice.

“For rare diseases such as hemophilia, gathering evidence from clinical practice is crucial to advance treatment and reduce gaps in patient care,” Margareth Ozelo, PhD, director of the WFH International Haemophilia Training Centre at the University of Campinas, in Brazil, said in a press release.

“These data add to the body of evidence for the management of hemophilia, and reinforce the value of using evidence from real world settings to personalized care, improve patient outcomes, and address the unique needs of every single patient,” Ozelo added.

In one of the posters, titled “7th Interim Analysis of Antihemophilic Factor (Recombinant) And Joint Health in Patients With Hemophilia A: AHEAD International” (ABS034), investigators reported seven-year data from a real-world study that aimed to evaluate the long-term safety and effectiveness of Advate at lowering the number of spontaneous bleeds in people with moderate or severe hemophilia A. Specifically, these patients had factor VIII (FVIII) activity levels up to 5%.

Originally developed by Shire, now part of Takeda, Advate is a man-made (recombinant) form of FVIII, the clotting protein missing or defective in people with hemophilia A. By providing patients with an artificial version of FVIII, Advate is expected to reduce the number of spontaneous bleeding episodes these patients experience.

AHEAD International is one of the largest, long-term, real-world studies ever carried out in patients with hemophilia. Previous six-year data from this study, and a similar one underway in Germany (DRKS00000556), supported Advate’s long-term safety and effectiveness at controlling bleeds in individuals with moderate or severe hemophilia.

Now, investigators reported data from an interim analysis of AHEAD International that included seven-year data from 711 patients, ages newborn to 78, who received Advate as a preventive or on-demand treatment to control their bleeds.

Data gathered until June 30, 2020, showed that when given prophylactically, Advate was superior to on-demand treatment at lowering the number of annual bleeds — assessed by the annualized bleeding rate (ABR) — in patients with moderate (0.0–1.0 vs. 1.8–6.7) and severe hemophilia (0.0–1.8 vs. 1.6–14.8).

Likewise, preventive treatment with Advate was more effective than on-demand treatment at lowering the number of annual bleeds occurring in the joints of patients with moderate and severe disease. This was assessed using the annualized joint bleeding rate (AJBR) in people with moderate ( 0.0–0.0 vs 0.7–3.8) and severe hemophilia (0.0–0.0 vs 0.7–8.9).

In addition, the percentage of patients who experienced no bleeding episodes over the years was much higher among those receiving preventive treatment than in those who used the therapy on demand. This was true in both individuals with moderate (40–63% vs. 23–50%) and severe disease (32–54% vs. 17–40%).

Safety assessments revealed that more than half of the patients (59.4%) experienced side effects, including 12 (1.7%) who developed FVIII inhibitors — neutralizing antibodies against the therapy — over the course of the study.

In another poster, this one titled “Real World Bleeding Rates Over 7 Years Of Antihemophilic Factor (Recombinant) in Patients With Hemophilia A And Target Joints: AHEAD International” (ABS170), the researchers presented data from a separate analysis of the same study that focused on Advate’s long-term safety and effectiveness. This analysis involved people with moderate or severe hemophilia with target joints, meaning those who had four or more bleeds occurring in the same joint within six months, or more than 20 bleeds occurring in the same joint over their entire life.

The results showed that the proportion of those with severe hemophilia A who experienced no joint bleeds over seven years was higher with prophylactic than with on-demand treatment (41–69% vs. 0–40%). Similar results were observed for those with moderate disease.

Preventive treatment also was more effective than on-demand Advate at keeping AJBRs low over the years in people with severe disease (0–0.9 vs. 5.6–15.2). The same tendency was found in patients with moderate hemophilia.

A third poster, titled “A Retrospective Study of the Impact of Switching Patients With Hemophilia A to Rurioctocog Alfa Pegol or Emicizumab in US Practice” (ABS039), reported the investigators’ findings from a study involving hemophilia A patients without FVIII inhibitors. That retrospective study evaluated the consequences of switching people with moderate or severe hemophilia A without FVIII inhibitors from standard FVIII replacement therapies to preventive treatment with Hemlibra (emicizumab) or Adynovate (rurioctocog alfa pegol).

Also marketed by Takeda, Adynovate is an FVIII replacement therapy similar to Advate. The difference is that the recombinant FVIII in its composition is attached to a polymer, called polyethylene glycol (PEG), that enhances its stability and allows it to remain active in the blood for longer periods of time.

In contrast, Hemlibra is an antibody-based therapy originally developed by Chugai Pharmaceutical and now marketed by Genentech that mimics the normal function of FVIII. It is currently approved as a routine prophylactic treatment for hemophilia A in several countries worldwide.

Data showed that after switching to Hemlibra or Adynovate, patients started experiencing fewer bleeds per year. However, no statistically significant differences were found between these two treatments regarding their effectiveness at controlling bleeds.

In addition to these posters, Takeda also presented data from other studies. Those findings further reinforced the safety and effectiveness of its hemophilia therapies, including Feiba, in a real-world setting, the company said.