Bioverativ

Eloctate and Alprolix Show Long-Term Effectiveness for Hemophilia in Extension Studies

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Eloctate and Alprolix Show Long-Term Effectiveness for Hemophilia in Extension Studies

Treatment of severe hemophilia A with Eloctate and hemophilia B with Alprolix was safe and improved the patients’ annualized bleed rates (ABRs) over four years, according to the results of two extension studies announced by Bioverativ and Sobi.

The two open-label extension studies — ASPIRE (NCT01454739), and B-YOND (NCT01425723) — evaluated long-term preventive treatment with the two therapies in previously treated adult, adolescent, and pediatric patients. The lower ABRs included joint bleeds and were observed across all patient populations and at extended dosing intervals.

According to the team, the findings support the idea that preventive treatment with Eloctate – marketed as Elocta in Europe and the Middle East – and Alprolix is effective in the management of all types of joint bleeds.

Safety data was consistent with the pivotal Phase 3 trials. No patient showed development of inhibitors, a serious complication for people with hemophilia treated with clotting factors.

The results were presented at the recent 60th Annual Meeting of the American Society of Hematology in San Diego.

“These data add to a significant body of evidence showing that Eloctate and Alprolix provide protection from all types of hemophilia-related bleeds with individualized and flexible dosing regimens across all study populations,” Tim Harris, PhD, executive vice president, research and development at Bioverativ, said in a press release. “We remain focused on and committed to providing complete protection for people with hemophilia.”

Both Eloctate and Alprolix are engineered extended half-life blood clotting factors. Half-life refers to the time the body takes to halve the amount of a compound. The two therapies had previously shown efficacy in all treatment situations, such as acute, surgical, and emergency situations.

The therapies are marketed by either Bioverativ, a Sanofi company, or Sweden-based Sobi, depending on the region of the world.

ASPIRE included participants who had completed the pivotal, Phase 3 A-LONG (NCT01181128) or Kids A-LONG (NCT01458106) studies. It enrolled 211 male patients, 150 from A-LONG and 61 from Kids A-LONG. The primary objective was the development of inhibitors. Secondary goals included the annualized number of bleeding episodes, Eloctate’s exposure days, and the participants’ assessment of treatment response.

Results showed that treatment with Eloctate enabled low overall median ABRs throughout the study, especially in patients on individualized dosing. Some of these patients (across all age groups) demonstrated zero spontaneous joint bleeds. In addition, median joint ABRs of less than 0.66 were shown in the different groups.

Adults and adolescents experienced an improvement in joint health, as shown by a mean modified hemophilia joint health (mHJHS) score of -2.5 (a negative value means improvement) compared with initial values in A-LONG. The mHJHS score grades joints by specific domains that include swelling, muscle atrophy (shrinkage), alignment, range of motion, joint pain, strength, and global gait. The team cautioned that further studies will be needed to confirm these results.

More than 92% of participants either lengthened or had no difference in dosing intervals during the course of ASPIRE. Overall, the low ABRs and the improved joint health illustrate a clinical benefit that goes beyond bleed prevention, according to the scientists.

B-YOND included patients who completed the Phase 3 B-LONG (NCT01027364) or Kids B-Long (NCT01440946) trials. It enrolled 116 previously treated males — 93 from B-LONG, and 27 from Kids B-LONG. Results from these studies supported an update to Alprolix’s label to include pediatric data.

Similar to ASPIRE, the primary outcome was development of inhibitors. Secondary goals were the annualized number of bleeding episodes, including spontaneous joint bleeding rates, Alprolix’s exposure days and consumption, and the participants’ assessment of response to treatment.

As in ASPIRE, ABRs were low during the study in all ages, particularly in joint and spontaneous joint bleeds. Median joint and spontaneous joint ABRs were lower than 1.58 and 0.38, respectively, in adults and adolescents on preventive treatment with Alprolix. These values were under 0.85 and zero in participants younger than 12.

Additionally, 85% of adults and 93% of pediatric patients either lengthened or had no change in dosing intervals during B-YOND. Overall, treatment with Alprolix provided flexible dosing associated with consistently low bleeding rates with extended interval dosing of up to 14 days.

According to the researchers, B-YOND reflects the real-life use of Alprolix, with dosing changes based on patient preferences and their clinical profile and needs.

FDA Accepts Bioverativ’s Investigational New Drug Application for BIVV001 to Treat Hemophilia A

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FDA Accepts Bioverativ’s Investigational New Drug Application for BIVV001 to Treat Hemophilia A

The U.S. Food and Drug Administration (FDA) has accepted Bioverativ’s investigational new drug application (IND) for BIVV001, an investigational Factor VIII therapy designed to extend protection from bleeds in hemophilia Apatients.

The FDA will now review the IND application for safety. The Waltham, Massachusetts-based company plans to initiate a Phase 1/2A clinical trial evaluating BIVV001 later this year.

BIVV001 (also known as rFVIIIFc-VWF-XTEN) provides once-weekly or longer prophylactic dosing for hemophilia A patients. It is the only investigational Factor VIII therapy in clinical development to overcome the von Willebrand factor ceiling, which is believed to impose a half-life limitation on current Factor VIII therapies. BIVV001 builds on the company’s Fc fusion portfolio, constructing the therapy in such a way that its time in circulation may be longer.

“People with hemophilia A continue to have a strong unmet need for therapies that can provide protection from bleeds and favorable long-term outcomes in terms of joint health and quality of life with once-weekly dosing,” Tim Harris, executive vice-president of R&D at Bioverativ, said in a press release. “In 2014, we made significant progress toward this goal with the introduction of Eloctate, the leading extended half-life therapy for hemophilia A. This IND acceptance expands on that legacy.”

Hemophilia A, also called factor VIII (FVIII) deficiency, is a genetic disorder caused by missing or defective Factor VIII, a clotting protein. Although it is passed down from parents to children, about one-third of cases are caused by a spontaneous mutation. The disease occurs in about one of 5,000 live births, according to the U.S. Centers for Disease Control and Prevention. About 20,000 Americans have hemophilia.

Rob Peters, senior vice-president of research at Bioverativ, said BIVV001 is the first molecule of its kind to fuse four proteins together to fight hemophilia A.

“We are encouraged by our extensive preclinical data which show improved pharmacokinetics that are independent of von Willebrand factor,” he said, “and look forward to commencing our Phase 1/2a clinical trial later this year.”