Clinical Trials

Date: 2017-12-10

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the World Federation of Hemophilia (WFH) 2016 World Congress in Orlando, Florida

Company: Bioverativ (USA - CA) Swedish Orphan Biovitrum SOBI (Sweden)

Product: Elocta®/Eloctate® (long-lasting recombinant Factor VIII Fc fusion protein - rFVIIIFc - efmoroctocog alfa)

Action mechanism:

• protein/coagulation factor. Eloctate® (efmoroctocog alfa) is an investigational, recombinant clotting factor therapy developed for hemophilia A by fusing factor VIII to the Fc portion of immunoglobulin G subclass 1, or IgG1 (a protein commonly found in the body). It is believed that this enables Eloctate® to use a naturally occurring pathway to prolong the time therapy remains in the body. While Fc fusion has been used for more than 15 years, Biogen Idec is the only company to apply it to the treatment of hemophilia.

Disease: hemophilia A

Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases

Country: Australia, Austria, Belgium, Brazil, Canada, France, Germany, Hong Kong, India, Ireland, Israel, Italy, Japan, The Netherlands, New Zealand, Poland, South Africa, Spain, Sweden, Switzerland, UK, USA

Trial details:

• ASPIRE is a multi-year extension study for people who completed the pivotal, phase 3 A-LONG or Kids A-LONG studies. The primary objective of the study is to evaluate the long-term safety of recombinant human Factor VIII Fc fusion protein (rFVIIIFc) in participants with hemophilia A. The secondary objective of the study is to evaluate the efficacy of rFVIIIFc in the prevention and treatment of bleeding episodes in participants with hemophilia A. The study enrolled 211 males, including 150 (98 percent) of those who completed A-LONG and 61 (91 percent) of those who completed Kids A-LONG. (NCT01454739)

 

Latest news:

• • On December 10, 2017, Swedish Orphan Biovitrum and Bioverativ announced the results of a new, post-hoc, longitudinal analysis of the pivotal Phase 3 A-LONG study and ASPIRE long-term extension study, showing that weekly prophylactic dosing with its extended half-life therapy Elocta® (efmoroctocog alfa) marketed as Eloctate® [Antihemophilic Factor (Recombinant), Fc Fusion Protein] in the US, has the potential to provide improved bleed protection over episodic treatment, resolve target joints and reduce the treatment burden associated with more frequent dosing intervals. The analysis is being presented in a poster session at the 59th Annual Meeting of the American Society of Hematology.
• Elocta was developed using Fc fusion technology to prolong circulation in the body and its efficacy and safety have been studied in haemophilia A patients since 2010. This new, post-hoc analysis supports a growing body of clinical data showing prophylactic treatment with Elocta can positively impact long-term joint health. Elocta is currently not indicated for weekly dosing.
• Prophylactic treatment with factor therapy is recognized as the optimal therapy for severe haemophilia A, yet, according to the World Federation of Hemophilia guidelines, this treatment regimen traditionally involves injections three times per week with conventional factor based products. With Elocta’s extended half-life, patients can extend dosing intervals up to five days resulting in less frequent injections. Using data spanning four years from the pivotal Phase 3 A-LONG study, and ASPIRE, the long-term extension study, researchers examined subjects who were exposed to a seven-day dosing (65 IU/kg/wk) interval to assess long-term outcomes as determined by annualized bleeding rates (ABR), adherence and resolution of target joints.
• In the study, 43 adults and adolescents (?>12 years) were exposed to an Elocta weekly dosing interval for a median study duration of 3.1 years. Researchers also analysed results of those who maintained a weekly dosing interval throughout the study period (n=19).
• For those subjects in the ever-on-weekly dosing group who had pre-study episodic treatment (n=32), transition to weekly prophylaxis dosing resulted in a change in median ABR (IQR) of -23.7 (-35.8, -12.8). For those subjects who were always on a weekly dosing regimen throughout the study period (n=19), the median pre-study ABR (IQR) for subjects on a pre-study episodic regimen was 29 (18, 45) compared to an on-study ABR (IQR) of 1.7 (0.5, 6.7). Subjects experienced protection from spontaneous bleeds (median spontaneous ABR (IQR) of 1.2 (0.2, 2.8) for subjects ever-on-weekly dosing and 0.7 (0, 1.6) for subjects always-on-weekly-dosing and from spontaneous joint bleeds (median ABR (IQR) of 0.8 (0, 2.5) in subjects ever-on-weekly dosing and 0.2 (0, 1.0) in subjects always-on-weekly-dosing).
• All subjects were highly adherent while on the weekly dosing regimen (median duration of 3.1 years) and among subjects who chose to initiate a weekly dosing regimen on Elocta at any point of the study, the majority stayed on weekly dosing. One hundred percent of all evaluable target joints in both the ever-on-weekly dosing group and always-on-weekly dosing group resolved during the study period. Study findings suggest weekly dosing may be a reasonable prophylaxis regimen for patients receiving episodic treatment, who would prefer the benefit of prophylaxis and better bleed protection, but with minimal treatment burden.
• • On October 31, 2017, Bioverativ and Swedish Orphan Biovitrum announced the publication of interim results from a longitudinal study of joint health in patients treated prophylactically with Eloctate®, for treatment of hemophilia A. Interim data show participants enrolled in the ASPIRE extension study demonstrated continuous improvement in joint health over a nearly three-year period with prophylactic dosing of Eloctate® , regardless of prior treatment regimen, severity of joint damage or target joints. Joint health improvements were most notable in hemophilia A patients with poor joint health. These results were published online October 30, 2017 in Haemophilia.
• This interim post hoc analysis evaluated joint health in adult and adolescent participants in the A-LONG and ASPIRE studies using a modified version of the Hemophilia Joint Health Score (mHJHS), a first-line assessment tool that grades joints by specific domains, including swelling, muscle atrophy, alignment, range of motion, joint pain, strength and global gait. The study examined mHJHS measurements (a decrease in score reflecting improvement, max=116) taken at A-LONG baseline and ASPIRE baseline and annually thereafter for nearly three years of treatment.
• In the study, adults and adolescents (n=47) treated prophylactically with Eloctate® experienced a mean improvement in joint health score of -4.1 at ASPIRE Year 2, compared with A-LONG baseline. Regardless of pre-study treatment regimen, subjects showed continuous improvement in mHJHS from A-LONG baseline through ASPIRE Year 2 (pre-study prophylaxis: -2.4; pre-study episodic treatment: -7.2) and benefits were seen in subjects with target joints (-5.6) as well as those with severe joint destruction (-8.8). The mHJHS components with the greatest improvement at ASPIRE Year 2 were swelling (-1.4), range of motion (-1.1) and strength (-0.8).
• • On July 18, 2016, Biogen and Swedish Orphan Biovitrum (Sobi™) will present updated data on long-term safety and efficacy of Elocta® (efmoroctocog alfa) (marketed as Eloctate® in the US and other regions outside of Europe) for haemophilia A and Alprolix® (eftrenonacog alfa) for haemophilia B. The data from the phase 3 extension studies, B-YOND (haemophilia B) and ASPIRE (haemophilia A), will be highlighted in oral and poster presentations at the World Federation of Hemophilia (WFH) 2016 World Congress in Orlando, Florida, from 24-28 July 2016.
• • On December 8, 2015, Biogen and Swedish Orphan Biovitrum (Sobi) have presented new data at the 57th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Fla. These data demonstrate Elocta®/Eloctate® (efmoroctocog alfa) [recombinant human coagulation factor VIII, Fc fusion protein]) and Alprolix® (rFIXFc) may effectively manage target joint bleeding and maintain low annualised bleeding rates (ABRs) in people with severe haemophilia A and B. For people with severe haemophilia A and B, most bleeding events occur in joints. When bleeding events occur repeatedly in the same joint (known as a target joint), it is often a precursor to chronic joint disease, marked by progressive deterioration of the joint. These post-hoc analyses aimed to assess the frequency of bleeding events and the dosing of Elocta and Alprolix in study participants who had one or more target joint bleeds [major joint (e.g., knee, elbow, ankle) with three or more bleeding episodes in a three-month (haemophilia B) or six-month (haemophilia A) period]. In this ASPIRE (an ongoing extension of phase 3 pivotal trials A-LONG and Kids A-LONG) post-hoc analysis, for people with haemophilia A taking Elocta® prophylactically, on-study ABRs overall and in target joints were lower than pre-study bleeding rates. Data from ASPIRE showed that nearly half of the adult and adolescent participants in the weekly prophylaxis, individualised prophylaxis and modified prophylaxis arms (n=26, n=82, n=12, respectively) did not have any target joint bleeds. For children, 53.8 per cent of participants in the individualised prophylaxis group (n=13) did not have any target joint bleeding episodes (42.3, 47.6 and 41.7 per cent, respectively). In addition, nearly all (97.4 per cent) target joints in adult and adolescent participants taking Elocta® were resolved during the follow-up period, suggesting that the therapy may be equally effective for preventing target joint bleeding episodes in weight-bearing and non weight-bearing joints. The median dosing intervals for ASPIRE participants with target joints at baseline were similar to those for the A-LONG and Kids A-LONG overall population.
• • On August 10, 2015, Biogen and  Swedish Orphan Biovitrum SOBI announced that newly published clinical data demonstrate that people on extended-interval prophylaxis regimens with Eloctate® [Antihemophilic Factor (Recombinant), Fc Fusion Protein] experienced low bleeding rates. The interim results of this Phase 3, open-label extension study called ASPIRE were published in the online edition of Haemophilia, the journal of the World Federation of Hemophilia, the European Association for Haemophilia and Allied Disorders, and the Hemostasis & Thrombosis Research Society. Study participants completing the Phase 3 A-LONG and Kids A-LONG studies were eligible to participate in ASPIRE. The results to-date show the majority of participants in ASPIRE, maintained or extended their dosing intervals between treatments compared to the A-LONG and Kids A-LONG studies. As of the interim analysis, the median time in the ASPIRE study was 80.9 weeks for adults and adolescents completing the A-LONG study, and 23.9 weeks for children completing the Kids A-LONG study. Inhibitor development is the primary endpoint of ASPIRE and no inhibitors were reported in any treatment groups. Through the interim ASPIRE analysis, adults and adolescents experienced annualized bleeding rates (ABRs) of 0.66, 2.03 and 1.97 in the individualized, weekly and modified prophylaxis arms, respectively. Children on individualized prophylaxis also experienced low bleeding rates, with an overall median ABR of 0.0 in children less than 6 years of age, and 1.54 for children ages 6 to 12. These results were consistent with data from the Phase 3 A-LONG and Kids A-LONG studies.
• In addition to efficacy and safety endpoints, the publication also reports changes in prophylactic infusion frequency from the end of the A-LONG study through the interim analysis. Of the adults and adolescents who had previously been treated prophylactically and who remained in the study through the interim analysis (n=128), 72 percent maintained their prophylactic dosing interval and 22 percent lengthened and six percent shortened the time between infusions. Extension study participants could change treatment group at any time.
• In ASPIRE, most participants received prophylactic treatment and were able to maintain protection against bleeding episodes with ELOCTATE consumption that was consistent with that observed in A-LONG and Kids A-LONG. The publication reported cumulative duration of treatment from the beginning of the A-LONG and Kids A-LONG studies through the ASPIRE interim data analysis. The median cumulative duration of treatment was 117.7 weeks for adults and adolescents, and 51.5 weeks for children less than 12 years old. Across age groups, safety results were consistent with the general hemophilia A population. There were no reports of serious allergic reactions or vascular clots. The most common adverse events (incidence of greater than or equal to five percent) included nasopharyngitis (common cold), arthralgia (joint pain) and upper respiratory infection.
• • On June 18, 2015, Swedish Orphan Biovitrum (Sobi) and Biogen announced that they will present 23 company-sponsored platform and poster presentations at the International Society on Thrombosis and Haemostasis (ISTH) 2015 congress taking place in Toronto, Canada, 20-25 June 2015. Data presented include an interim analysis from the ASPIRE study focussing on the long-term safety and efficacy of Eloctate®/Elocta®/rFVIIIFc [Antihemophilic Factor (Recombinant), Fc Fusion Protein] for the prevention and treatment of bleeding in previously treated adults and adolescents with haemophilia A. Eloctate/Elocta-focused abstracts:  Safety and efficacy of recombinant factor VIII fusion protein (rFVIIIFc) for the prevention and treatment of bleeding in previously-treated adult and adolescent subjects with haemophilia A: Interim analysis of the ASPIRE study - Poster #235
• Treatment of bleeding with recombinant factor VIII Fc fusion protein in previously-treated paediatric subject with haemophilia A in the phase 3 Kids A-LONG study - Poster #239 -
• Indirect comparisons of factor consumption, bleeding rates, and infusion frequencies during routine prophylaxis with recombinant factor VIII Fc fusion protein and other recombinant factor VIII products - Poster #170.

Is general: Yes