rVIIa-FP (CSL689) / CSL Behring - LARVOL DELTA

Pharmacokinetics and pharmacodynamics of a recombinant fusion protein linking activated coagulation factor VII with human albumin (rVIIa-FP) in patients with congenital FVII deficiency. (PubMed, Hematology) - P1 | "Patients received their routine FVII product (30 IU/kg plasma-derived FVII [pdFVII] or 25 μg/kg recombinant activated FVII (rFVIIa) [eptacog alfa]), and were then randomly assigned to receive 100 or 300 μg/kg of rVIIa-FP. Analysis of PD data showed a sustained suppression of lag time below 4.5 min (upper limit of healthy people) for rVIIa-FP compared to rFVIIa. AUEC and EC were similar across the two dose groups of rVIIa-FP and rFVIIa. rVIIa-FP was well tolerated in patients with congenital FVII deficiency, showed a longer half-life and lower clearance compared to rFVIIa, and lag time remaining within healthy ranges for ≥8 hr. These results warrant further investigation into the efficacy of rVIIa-FP to control and prevent bleeding in patients with FVII deficiency."

Clinical • Journal • PK/PD data • Hematological Disorders • Hemophilia

CSL: Investor R&D Briefing (CSL Behring) - "100% of bleeds controlled with 2 infusions"

P2/3 data • Hemophilia

CSL Behring: R&D Briefing (CSL Behring) - Anticipated initiation of P2/3 trial in patients with hemophilia A & B with inhibitors in H1 2015

Anticipated new P2/3 trial • Hemophilia

CSL: Investor R&D Briefing (CSL Behring) - "Phase I study confirms rVIIa-FP has measurable FVIIa levels up to 48 hrs"

P1 data • Hemophilia

Safety and pharmacokinetics of a recombinant fusion protein-linking coagulation factor VIIa with albumin (rVIIa-FP) in healthy volunteers (ISTH 2013) - Abstract #PB 3.37-5; P1, N=40; Sponsor: CSL Behring; NCT01542619; "FVIIa baseline-corrected mean (SD) C max plasma activity increased in a dose-proportional manner, from 9240 (515) mU/mL for the 140 lg/kg dose to 63520 (13515) mU/ mL for the 1000 lg/kg dose."

P1 data • Hemophilia

CSL: Investor R&D Briefing (CSL Behring) - Anticipated initiation of P2 trial in congenital hemophilia factor VII deficiency in H2 2017; Anticipated launch for on-demand treatment and prophylaxis in hemophilia in 2021

Anticipated launch • Anticipated new P2 trial • Hemophilia

CSL Behring presents phase I results from study of recombinant fusion protein linking coagulation factor VIIa with albumin (rVIIa-FP) in healthy volunteers (CSL Behring Press Release) - P1, N=40; Sponsor: CSL Behring; NCT01542619; "With our recombinant albumin fusion technology, we believe we have an innovative and promising approach that may yield long-acting therapies with the potential to truly advance hemophilia treatment."

P1 data • Hemophilia

Study of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) for On-demand Treatment of Bleeding Episodes in Patients With Hemophilia A or B With Inhibitors (clinicaltrials.gov) - P2/3; N=54; Not yet recruiting; Sponsor: CSL Behring

New P2/3 trial • Phase shift • Biosimilar • Hematological Malignancies • Hemophilia

CBER new biologic tally healthy in 2013, but for innovation look to 2014 (Pink Sheet - Informa) - CSL-689 Phase II/III trial to start in hemophilia patients with inhibitors in 2014. Anticipated Phase I/III study completion in early 2014 with BLA following in early 2015 for CSL-627. BAX-855 expects to file in late 2014. Alprolix PDUFA date already extended to Q1 2014. CSL-654 BLA submission expected in early 2015.

Anticipated BLA • Anticipated new P2/3 trial • Anticipated PDUFA date • Anticipated trial completion date • Hemophilia

Study of Recombinant Factor VIIa Fusion Protein (rVIIa-FP, CSL689) for On-demand Treatment of Bleeding Episodes in Patients With Hemophilia A or B With Inhibitors (clinicaltrials.gov) - P2/3; N=54; Recruiting; Sponsor: CSL Behring; Trial primary completion date: Dec 2018 ➔ May 2019

Trial primary completion date • Biosimilar • Gene Therapies • Hematological Malignancies • Hemophilia

Pharmacodynamic Efficacy of a Recombinant Fusion Protein Linking Activated Factor VIIa to Human Albumin (rVIIa-FP) in FVII Depleted Plasma (ISTH 2017) - "The study demonstrates comparable correction of key coagulation parameters by rVIIa-FP and rFVIIa in a FVII deficient in vitro system. Current clinical trials are evaluating rVIIa-FP's potential for improving treatment of FVII deficient patients."

Biosimilar • Venous Thromboembolism