Encore - emicizumab prophylaxis for the treatment of infants with severe hemophilia A without Factor VIII inhibitors: results from the interim analysis of the HAVEN 7 study

Introduction Emicizumab (emi) prophylaxis can be started from haemophilia A (HA) diagnosis, reducing bleeding risk in infants with HA (IwHA). This interim analysis (IA) of HAVEN 7 (NCT04431726) evaluates the efficacy, safety and pharmacokinetics (PK) of emi in IwHA1.

Method HAVEN 7 is a Phase 3b, open-label study of emi in IwHA ≤12 months (m) without FVIII inhibitors. IwHA receive emi 3mg/kg weekly for 4 weeks (wks), then 3mg/kg every 2 wks for 52 wks; IwHA can then stay on this dose or switch to 1.5mg/kg weekly or 6mg/kg every 4 wks for the 7-year follow-up. Endpoints include: efficacy (treated bleeds; all bleeds; treated spontaneous bleeds; treated joint bleeds); safety; PK; and anti-emi antibodies (ADAs). Annualised bleed rates (ABR) are estimated using a negative binomial regression model.

Results At the IA cut-off (March 31, 2022),54 IwHA (55.6% ≥3–≤12m; 44.4% <3m; all male) had ≥1 dose of emi; median (range) age: 4.5 (0–11) m at baseline; 16 (1–26) m at cut-off. Minimally treated (≤5 exposure days with HA-related treatments (i.e., FVIII, plasma, cryoprecipitate or whole blood products)): 55.6%; previously untreated: 44.4%. Median (range) treatment duration: 42.1 (1–60) wks.Overall, 77 bleeds occured in 31 IwHA: 88.3% traumatic; 5.2% procedural; 6.5% spontaneous.One IwHA had 12 bleeds (all traumatic; none joint/muscle; none treated). Overall, 14 treated bleeds, all traumatic, were reported in 12 IwHA. No IwHA had >2 treated bleeds. Mean model-based ABR (95% confidence interval [CI]) for treated bleeds, all bleeds and treated joint bleeds were 0.4 (0.23–0.65), 1.9 (1.35–2.68) and 0.1 (0.01–0.22), respectively. In all, 77.8% of IwHA had zero treated bleeds, while 42.6% had no bleeds at all. In total, 92.6% of IwHA had ≥1 adverse event (AE); 16.7% of AEs were emi-related injection-site reactions. No AEs led to changes in or withdrawal from emi. Eight IwHA reported 12 serious AEs; none were considered emi-related. No deaths/thrombotic events/thrombotic microangiopathies have been reported. None of the 48 IwHA evaluable for immunogenicity tested positive for ADAs. Evaluable PK data in 52 IwHA showed mean trough concentrations of emi increased during loading and were maintained thereafter, slightly above 60µg/mL.[1]

Conclusion This IA indicates that emi is efficacious and well tolerated in IwHA without FVIII inhibitors.

 

Scroll to top

Conflict of Interest

CEE has acted as a consultant, and received speaker’s fees and/or research funding from Bayer, Biomarin, Biotest, Chugai, CSL Behring, Grifols, Kedrion, LFB, Octapharma, Novo Nordisk, Pfizer, Roche, Sobi, Takeda. PC reported Grant/Research support/Funding statement: Research support from CSL Behring. Consultant: CSL Behring, Roche, Novonordisk. Membership on an entity’s board of directors or advisory committees: Member of HAVEN7 steering committee. DC reported Employment: Roche Pharmaceuticals (Basel, Switzerland). KG reported Grant/Research support/Funding statement: BSF, Opko Biologics, Pfizer, Roche, Shire. Consultant: ASC therapeutics, Bayer, Biomarine, Novonordisk, Pfizer, Roche, Sanofi-Genzyme,Sobi, Takeda, Uniquore. Employment: Sheba Medical Center, Tel Hashomer, Israel; Tel Aviv University. Honoraria: Bayer, BioMarin, BPL, CSL, Pfizer,Novonordisk, Roche, Sanofi- Genzyme, Sobi, Spark, Takeda, Uniquore. Membership on an entity’s board of directors or advisory committees: PedNet foundation. CS reported Shareholder and Employment F. Hoffmann - La RocheLtd. MB reported Shareholder and Employment F. Hoffmann-La Roche AG. FP reported Honoraria Educational meetings: Grifols, Roche. Membership on an entity’s board of directors or advisory committees: Advisory boards: Sanofi, Sobi, Takeda, Roche, Biomarin. GY reported Grant/Research support/Funding statement: Genentech, Grifols, Takeda. Consultant: Bayer, Biomarin, CSL Behring, Genentech/Roche, LFB, Novo Nordisk, Pfizer, Sanofi, Spark, Takeda. Speakers’ Bureau: Biomarin, Genentech, Hema Biologics, Sanofi, Spark. Honoraria: Bayer, Biomarin, CSL Behring, Genentech/Roche, Novo Nordisk, Pfizer, Sanofi, Spark, Takeda. Patents/Royalties: Viatris. JO has received research funding from Bayer, Biotest, CSL Behring, Octapharma, Pfizer, Swedish Orphan Biovitrum, and Takeda; consultancy, speakers bureau, honoraria, scientific advisory board, and travel expenses from Bayer, Biogen Idec, BioMarin, Biotest, Chugai Pharmaceutical Co., Ltd., CSL Behring, Freeline, Grifols, Novo Nordisk, Octapharma, Pfizer, F. Hoffmann-La Roche Ltd., Sanofi, Spark Therapeutics, Swedish Orphan Biovitrum, and Takeda. MEM acted as paid consultant, speaker and/or advisor for Bayer, Biomarin, CSL Behring, Grifols, Kedrion, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Spark Therapeutics, Sobi, Takeda and UniQure. AK reported Shareholder and Employment F. Hoffmann-La Roche. TC reported Shareholder: F. Hoffmann-La Roche AG. Employment: Spark Therapeutics. ML reported Shareholder and Employment F. Hoffmann-La Roche. CJF reported Grant/Research support/Funding statement: CSL Behring, Novo Nordisk, SOBI. Consultant: SOBI, Sanofi, NovoNordisk, Roche. Membership on an entity’s board of directors or advisory committees: EAHAD.

• References

• 1 Pipe S, Collins P, Dhalluin C. et al. ASH 2022.

Publication History

Article published online:
20 February 2023