Advances in Hemophilia B Replacement and Gene Therapies Detailed at ASH Meeting

Two presentations at the 2016 American Society of Hematology Annual Meeting (ASH) highlight ongoing treatment advances for hemophilia B. The data suggest that life with hemophilia could soon become easier to manage.

Long-acting replacement therapy

The ASH meeting, held in San Diego on Dec. 3-6, was a platform for CSL Behring to present a new analysis of clinical trial data from its new long-acting compound Idelvion (recombinant coagulation factor IX).

Idelvion stays longer in the body than earlier factor IX compounds, allowing patients to go for greater intervals of time between dosing. This is achieved by fusing the blood clotting factor to the plasma protein albumin.

The study showed that patients who maintained levels of the factor above 5 percent had an up to 80 percent reduced risk of bleeding over one year.

Earlier studies demonstrated that Idelvion remains in the body at high levels when the drug is administered every seven days (21 percent), or 14 days (13 percent). The new analysis pooled data from the Phase 3 trials of the compound in the PROLONG-9FP program (NCT01496274 and NCT02053792).

Researchers report that the data obtained related to 478 bleeding episodes in 57 adult patients with hemophilia B. They estimated the activity levels of factor IX  by using available data on how the drug behaves in patients with both prophylactic and on-demand treatment. Patients receiving prophylactic treatment received the drug once every 7, 10, or 14 days.

The majority of bleeding episodes occurred during the on-demand phase of the studies, the researchers reported.

Data showed that the exposure to factor IX could predict the risk of bleeding. Patients who were treated for one year, and who had plasma levels of factor IX of more than 5% or more than 10%, had a significantly reduced risk of bleeding. Levels of more than 2% had no impact on bleeding reduction.

Idelvion is already approved in the U.S., Europe, Japan, Australia, Switzerland, and Canada.

“This new analysis of Phase III IDELVION clinical trials shows a strong association between high and prolonged factor IX levels and efficacy of IDELVION in reducing bleeding risk in adult hemophilia B patients,” John Roberts, PhD, director of clinical pharmacology, CSL Behring, and a lead investigator, said in a news release.

“These findings provide additional clinical rationale for targeting and maintaining factor IX trough activity levels above 5 or 10 percent to optimize treatment outcomes, aligning with World Federation of Hemophilia clinical guidelines for the management of hemophilia.”

A gene therapy approach

The other presentation took a different approach to hemophilia treatment. uniQure reported at ASH 2016 that its gene therapy AMT-060 — tested in 10 patients with severe or moderately severe hemophilia B — allowed the majority to quit replacement therapy, and significantly reduced the number of bleeding episodes among patients.

Researchers demonstrated that the treatment, a one-time infusion of the gene therapy, gave sustained factor IX activity for up to one year.

The ongoing Phase 1/2 clinical trial (NCT02396342) divided the patients into a low-dose and a higher-dose group. New data from the higher-dose group, followed for up to 31 weeks, showed that all four of these patients — who previously needed chronic replacement therapy — could stop the treatment.

Data presented also showed that only one episode of spontaneous bleeding was recorded after patients stopped taking factor IX replacement treatment.

Before the trial, the five patients in the low-dose group had uncontrolled bleeding despite replacement therapy. After receiving the gene therapy, their factor IX activity remained high throughout the 52 weeks of follow-up. The effects also seem to improve over time, as spontaneous bleeding in this group entirely stopped over the last 14 weeks.

“The data from this ongoing study demonstrate clinically significant and sustained increases in FIX activity, substantial reductions in FIX replacement usage and a near cessation of spontaneous bleeding episodes,” Frank W.G. Leebeek, MD, PhD, and a professor at the Erasmus University Medical Center in Rotterdam, the Netherlands, said in a news release.

“In total, we are observing a therapeutic benefit from AMT-060 that is clearly superior to their previous prophylactic FIX replacement therapy regimen, even in patients with advanced joint disease who still experienced many bleeds despite prophylaxis with FIX,” he added.

As the treatment is delivered with the help of viral vectors, patients were tested for the presence of antibodies to the virus before its start. Among 25 screened patients, only one had a borderline positive result for antibodies, suggesting this therapy may benefit a majority of hemophilia B patients.