vatreptacog alfa (NN 1731) / Novo Nordisk - LARVOL DELTA

The MHC Associated Peptide Proteomics assay is a useful tool for the non-clinical assessment of immunogenicity. (PubMed, Front Immunol) - "In this study, we employed MHC Associated Peptide Proteomics (MAPPS) to comprehensively evaluate the immunogenic potential of re-engineered variants of immunogenic FVIIa analog (Vatreptacog Alfa). Our finding revealed the correlation between the protein sequence affinity for MHCII and the number of peptides identified in a MAPPS assay and this further correlates with the reduced T-cell responses. Moreover, MAPPS enable the identification of "relevant" T cell epitopes and may contribute to the development of biologics with lower immunogenic potential."

Journal

Mitigation of T-cell dependent immunogenicity by reengineering factor VIIa analogue. (PubMed, Blood Adv) - "Vatreptacog alfa (VA), a recombinant activated human factor VII (rFVIIa) variant with 3 amino acid substitutions, was developed to provide increased procoagulant activity in hemophilia patients with inhibitors to factor VIII or factor IX...The reengineered rFVIIa analog variants retained increased intrinsic thrombin generation activity but did not elicit T-cell responses in peripheral blood mononuclear cells isolated from 50 HLA typed subjects representing the human population. Our algorithm, rational immunogenicity determination, offers a broadly applicable deimmunizing strategy for bioengineered proteins."

Biomarker • Journal • Hematological Disorders • Hemophilia • Rare Diseases

[VIRTUAL] KEYNOTE PRESENTATION: New Technologies and Approaches to Assess and Circumvent Immunogenicity (PEGS 2020) - "I will give examples how we: evaluated and re-designed immunogenic rFVIIa analog (Vatreptacog Alfa); redesigned variants exhibiting both desired functional activity and reduced immunogenicity-risk; evaluated plasma-derived FVIII vs. recombinant FVIII using the MAPPs assay; and gave the explanation for clinical findings. We have been developing new approaches and assays for immunogenicity assessments and applying these to specific proteins and immunogenicity issues. Thus, my talk will not only lay out the broad principles, but also provide specific examples where our approaches have been useful."

Efficacy and safety of NNC 0078-0000-0007 in patients with congenital haemophilia and inhibitors (adept 2) (clinicaltrials.gov) - P3, N=82; adept 2; Recruiting -> Active, not recruiting

Enrollment closed • Hemophilia

Pharmacogenetic Testing of Saliva Samples From Patients With Five or More Exposure Days to rFVIIa Analogue in the Adept™2 Trial (clinicaltrials.gov) - P=N/A; N=25; Enrolling by invitation; Sponsor: Novo Nordisk A/S

New trial • Biosimilar • Hemophilia

Novo Nordisk could drop blood drug candidate-exec (Reuters) - In Oct 2012 Novo Nordisk will have to drop vatreptacoq alfa unless they get the positive P3 results

Anticipated P3 data • Hemophilia

FY ′10 results (Novo Nordisk) -

NN1731/ Novonordisk; P3 program expected to start in mid-2011

Anticipated P3 trial initiation • None

Citi European Healthcare Conference (Novo Nordisk) - P2 data release

P2 data • Hemophilia

Novo Nordisk discontinues development of vatreptacog alfa following analysis of phase 3 results (Novo Nordisk) - Novo Nordisk has discontinued the development of vatreptacog alfa based on the analysis of P3a adept 2 data; Vatreptacog alfa & NovoSeven can stop a very high percentage of bleeding episodes, 93%, with three doses or less

Discontinued • Hemophilia

Multicentre, randomised, double-blinded, active controlled, cross-over phase 3 trial on safety and efficacy of rFVIIa analogue (vatreptacog alfa) in haemophilia patients with inhibitors (adept 2) (ISTH 2013) - Abstract #OC 83.2; P3, N=72; adept 2 (NCT01392547); Sponsor: Novo Nordisk; “Successful bleeding control…was similar for both vatreptacog alfa and rFVIIa, and was achieved in 93% of all treated bleeds with 1–3 doses. Vatreptacog alfa was superior to rFVIIa in several secondary efficacy analyses, including fewer doses used to treat a bleed and sustained bleeding control...”

P3 data • Hemophilia

Anti-drug antibody formation in haemophilia patients with inhibitors after receiving recombinant activated FVII analogue (vatreptacog alfa) (EAHAD 2013) - P3, N=72; adept 2 (NCT01392547); "The high incidence of antidrug antibody development observed after vatreptacog alfa exposure and the potential risks thereof should be taken into consideration for future development of rFVIIa-derived products...the largest trial to date with bypassing agents in inhibitor patients, indicate that even very small changes to the structure can significantly alter the immunogenicity profile of rFVIIa products."

P3 data • Hemophilia