Analytical comparability demonstrated for an IgG4 molecule, inclacumab, following transfer of manufacturing responsibility from Roche to Global Blood Therapeutics

ABSTRACT

Background

Inclacumab is a recombinant, fully human, immunoglobulin IgG4 monoclonal antibody that selectively binds to P-selectin. Initially discovered and developed by Roche through phase 2 clinical studies in peripheral arterial disease and coronary artery disease, inclacumab has been in-licensed by Global Blood Therapeutics (GBT) as a potential treatment to reduce the frequency of vaso-occlusive crises in individuals with sickle cell disease.

Research design and methods

GBT sought to demonstrate the analytical comparability between material produced by Roche and material produced by GBT to ensure that no meaningful differences in identity, safety, purity, potency, or bioavailability exist between the GBT and Roche lots.

Results

Inclacumab samples produced by GBT were found to be comparable to the Roche v0.2 inclacumab samples based on (1) comparable primary and higher-order structures; (2) comparable purity profiles; (3) comparable potency, in vitro functional activities, and in vivo plasma exposures and pharmacokinetic profiles; and (4) comparable degradation patterns and kinetics under forced degradation conditions.

Conclusions

Based on the design of this comparability study and the results obtained, the US Food and Drug Administration approved the changes to the manufacturing process and gave clearance for GBT to proceed with phase 3 clinical trials.

KEYWORDS:

• Comparability
• inclacumab
• monoclonal antibody
• P-selectin
• sickle cell disease
• vaso-occlusive crisis

Acknowledgments

We thank Nadine Ritter, PhD, for reviewing the manuscript. Medical writing and editorial assistance were provided by Lindsay Tannenholz, PhD (Healthcare Consultancy Group), funded by Global Blood Therapeutics.

Declaration of interest

R Mihaila, D Ruhela, L Xu, S Joussef, X Geng, AS Kim, W Yares, and K Furstoss are all employees of Global Blood Therapeutics. J Shi is a former employee of Global Blood Therapeutics. The current affiliation for J Shi is Ideaya Biosciences, South San Francisco, CA, USA. K Iverson is a consultant for Global Blood Therapeutics. Global Blood Therapeutics is a wholly owned subsidiary of Pfizer Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have received an honorarium from Expert Opinion on Biological Therapy for their review work, but have no other relevant financial relationships to disclose

Author contributions

Conceptualization: K Furstoss, K Iverson; methodology: R Mihaila, X Geng, J Shi; investigation: R Mihaila, L Xu, S Joussef, Xin G, J Shi; data curation: R Mihaila, D Ruhela, L Xu; visualization: R Mihaila, D Ruhela; writing – original draft preparation: R Mihaila, D Ruhela, K Iverson; writing – review and editing: all authors. All named authors meet the International Committee of Medical Journal Editors criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Data availability

The authors confirm that the data supporting the findings of this study are available within the article.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14712598.2022.2143260

Additional information

Funding

This paper was funded by Global Blood Therapeutics, a wholly owned subsidiary of Pfizer Inc.