Immunogenicity and safety of omalizumab in pre-filled syringes in patients with allergic (IgE-mediated) asthma

Abstract

Background:

Omalizumab, a humanised anti-immunoglobulin E monoclonal antibody for treatment of uncontrolled moderate-to-severe or severe persistent allergic asthma, was developed as a lyophilised powder for reconstitution. A liquid formulation in pre-filled syringes has now been developed. The purpose of this study was to assess the immunogenicity and safety of this liquid formulation.

Methods:

In this multinational, open-label, single-arm study, patients (≥12 years) with moderate-to-severe allergic asthma were treated for 24 weeks with the liquid formulation of omalizumab (75 or 150 mg in a pre-filled syringe) at 2 or 4 week intervals. Immunogenicity was assessed by measurement of human anti-therapeutic antibody (ATA) levels. Safety was assessed by monitoring adverse events (AEs), haematology, blood chemistry, urine analysis and vital signs.

Results:

A total of 155 patients were enrolled in the study. No patient had a confirmed positive ATA test result. Most frequent individual AEs were asthma (17.4%), sinusitis (17.4%) and upper respiratory tract infection (11.6%). Fourteen patients (9.0%) had serious AEs and there was one death (not treatment related). There were no cases of anaphylaxis according to Sampson criteria. Most patients remained within normal ranges for haematology and biochemistry laboratory variables.

Conclusions:

Omalizumab in pre-filled syringes was not associated with immunogenicity. This novel formulation, which does not require reconstitution, had a safety profile consistent with the lyophilised formulation. A limitation of this study is that efficacy of omalizumab in the treatment of asthma was not specifically addressed herein.

Clinicaltrials.gov identifier:

NCT00500539.

Key words::

• Asthma
• Immunogenicity
• Immunoglobulin E
• Omalizumab
• Safety

Transparency

Declaration of funding

This research was funded by Novartis Pharma AG, manufacturers of omalizumab.

Declaration of financial/other relationships

L.S. has received multiple research grants from Novartis, Genentech, GlaxoSmithKline, Merck, Schering, Astra Zeneca, Sanofi Aventis, Forest, Boehringer Ingelheim, Sepracor, Dey, Pfizer, Greer, Alcon, Meda, Naryx, Nycomed, MedicaNova, SkyePharma, Accentia, Teva and Johnson & Johnson. J.B. has received research funds from Novartis, Genentech, Amgen and Merck. P.D’A. is employed by Novartis and M.B. is a former employee of Novartis. G.P. and A.V. are employed by and own stocks in Novartis. All authors agree with the manuscript as written.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

Novartis provided financial support for the conduct of this research, and was involved in designing the studies, collecting, analyzing and interpreting the study data, writing the study reports, and the decision to submit this paper for publication. The authors were assisted in the preparation of the manuscript by Lisa Quinn MBChB (professional medical writer, CircleScience). Writing support was funded by the study sponsor.