Preventive treatment with Altuviiio better than Hemlibra: Analysis
Indirect comparison of Phase 3 trial data suggests potential treatment ‘shift’
Preventive treatment with Altuviiio (efanesoctocog alfa) provided better bleed prevention than Hemlibra (emicizumab) in adults and adolescents with hemophilia A, according to an indirect comparison of Phase 3 clinical trial data.
“While it should be borne in mind that this is an indirect comparison and, as such, there were inevitably some differences between the patient populations, the observations of apparently greater efficacy of [Altuviiio] compared with [Hemlibra] suggest potential for a shift in the treatment landscape for haemophilia A,” the researchers wrote.
The study, “Efanesoctocog Alfa Versus Emicizumab in Adolescent and Adult Patients With Haemophilia A Without Inhibitors,” was published in Advances in Therapy. It was funded by Sanofi, which markets Altuviiio in the U.S., and Sobi, which markets the therapy as Altuvoct in Europe and other markets.
Hemophilia A patients lack enough functional factor VIII (FVIII), an important blood clotting protein, leaving them vulnerable to prolonged, excessive, or spontaneous bleeding. Standard care involves preventive (prophylactic) treatments to reduce the risk of bleeds. That includes FVIII replacement therapies, such as Altuviiio, that provide patients with a version of the missing FVIII protein.
Altuviiio is modified to last longer in the body than standard replacement therapies, and is given via weekly infusions into the bloodstream. It’s approved in the U.S. for preventing and treating bleeds in adults and children with hemophilia A, with a similar indication in Europe. Regulatory approvals were backed by data from the Phase 3 XTEND-1 trial (NCT04161495) involving people with severe hemophilia A, ages 12 and older, which showed that Altuviiio led to better bleed control than prior prophylactic regimens.
Preventive treatment in a different form
Hemlibra is a different kind of prophylactic therapy that’s given via under-the-skin injections. Instead of providing a version of FVIII, it mimics the activity of the protein in the blood clotting cascade.
The therapy is approved in the U.S. for hemophilia A patients with or without inhibitors, neutralizing antibodies against FVIII that can render standard replacement therapies less effective, and in Europe for patients with or without inhibitors who have moderate or severe disease.
Its own approvals were supported by data from the HAVEN clinical trial program, including the Phase 3 HAVEN 3 trial (NCT02847637), which found the therapy significantly reduced bleeds in severe hemophilia A patients, ages 12 and older, without inhibitors.
There haven’t been any head-to-head trials comparing clinical outcomes with Altuviiio versus Hemlibra, so the researchers conducted an analysis to compare previously published data from the XTEND-1 and HAVEN 3 trials.
They performed a matching-adjusted indirect comparison (MAIC), a statistical method that allows the comparison of treatments from separate studies. It essentially weighted patient data from XTEND-1 to match that from HAVEN 3. Patients from XTEND-1 who didn’t match the population from HAVEN 3 were also removed.
Results showed that, among patients who had received prior prophylactic or on-demand treatment, weekly Altuviiio was associated with a significantly lower rate of overall bleeds — by around 70% — compared with weekly Hemlibra. It was also associated with about a 50% lower incidence of bleeds that required on-demand treatment, and treated joint bleeds.
Weekly Altuviiio also led to significantly lower rates of overall bleeds compared with Hemlibra given every other week among patients who previously received on-demand treatment.
Altuviiio was also associated with significantly greater joint health improvements than Hemlibra given every week or every other week.
“Collectively, [Altuviiio] was associated with improved efficacy versus [Hemlibra] for the treatment of adolescents and adults with severe haemophilia A without inhibitors,” the researchers wrote.
Other MAICs performed to indirectly compare Altuviiio with other factor replacement therapies have similarly favored Altuviiio, according to the study’s authors.
“Overall, these results show that [Altuviiio] is associated with significant clinical benefit over existing haemophilia therapies … and thus warrants consideration by healthcare professionals during clinical decision-making as a preferred option for prophylactic treatment of adults and adolescents,” the team wrote.
Indirect trial comparisons can’t ensure that the populations being studied are exactly matched. For example, patients in HAVEN 3 generally had a higher disease burden and were less likely to be receiving standard care at the start of the trial than those in XTEND-1. The researchers noted that MAIC is widely used when head-to-head data is not available, and despite these limitations, is still “the best available method for indirect comparison.”
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