Efficacy of HP-3070, A Once-Daily Asenapine Transdermal System, in the Treatment of Adults with Schizophrenia: A PANSS Five-Factor Analysis

Abstract

Introduction

HP-3070, a once-daily asenapine transdermal system, is the first antipsychotic “patch” formulation FDA approved for adults with schizophrenia. Positive and Negative Syndrome Scale (PANSS) score items can be grouped into a five-factor structure to describe specific schizophrenia symptom domains. This post hoc analysis of data from a pivotal study evaluated HP-3070’s efficacy by examining these factors.

Methods

In a phase 3 study, adults with an acute exacerbation of schizophrenia were randomized to six weeks of treatment with HP-3070 3.8mg/24h, 7.6mg/24h, or placebo. An analysis was performed using the five PANSS factor domains (negative symptoms, positive symptoms, disorganized thought, uncontrolled hostility/excitement, anxiety/depression). Mixed-model repeated-measures (MMRM) analysis included change from baseline (CFB) in PANSS factor score as the repeated dependent variable, with country, treatment, visit, treatment by visit interaction, and baseline PANSS score as covariates.

Results

The analysis included 607 patients. Treatment with HP-3070 3.8mg/24h resulted in a statistically significant LS mean CFB (improvement) vs placebo at Weeks 4–6 for all domains except for anxiety/depression, where a numerical difference was observed in favor of active treatments. Among the domains, the positive symptom factor demonstrated the numerically greatest LS mean (SE) difference from placebo in CFB, which for HP-3070 7.6mg/24h was −2.0 [0.57] and for HP-3070 3.8mg/24h was −2.3 [0.57]; P<0.001 for both. Treatment effect size for the positive symptom factor using Cohen’s d (95% confidence intervals) was 0.39 (0.17, 0.61) for HP-3070 7.6mg/24h and 0.45 (0.20, 0.64) for HP-3070 3.8mg/24h.

Discussion

Post hoc analysis using a PANSS five-factor model suggests that HP-3070 may address a broad range of symptoms in people with schizophrenia.

Keywords:

• asenapine
• transdermal
• patch
• schizophrenia
• positive and negative syndrome scale
• five-factor

Data Sharing Statement

The data that support the findings of this study are available from Noven Pharmaceuticals. Restrictions apply to the availability of these data. Data can be requested by emailing Noven at [email protected].

Ethics Statement

The study protocol was approved by an independent ethics committee or review board at each study center (for list of ethics committees, see Supplemental Table 1). Written informed consent was obtained from all participants. The study was conducted in accordance with the ethical principles derived from the Declaration of Helsinki.

Acknowledgments

The authors thank Sandeep Byreddy, MS, for his contributions to data analysis and the development of this manuscript. The authors thank Michelle L. Jones, PhD, MWC, and Anthony DiLauro, PhD, of PharmaWrite, LLC, for medical writing and editorial assistance, which were funded by Hisamitsu Pharmaceutical Co, Inc. This manuscript was prepared according to the International Society for Medical Publication Professionals’ “Good Publication Practice for Communicating Company-Sponsored Medical Research: The GPP3 Guidelines”. Data from this paper were presented as a poster at Psych Congress 2022 (September 17–20, 2022, New Orleans, LA) and at NEI Congress 2022 (November 3–6, 2022, Colorado Springs, CO) and were published in abstract form as Citrome L et al. CNS Spectr. 2023;28(2):243–244 (https://doi.org/10.1017/S1092852923001773).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and have agreed to be accountable for all aspects of the work.

Disclosure

Dr. Citrome served as a consultant to AbbVie/Allergan, Acadia, Adamas, Alkermes, Angelini, Astellas, Avanir, Axsome, Biogen, BioXcel, Boehringer Ingelheim, Cadent Therapeutics, Cerevel, Clinilabs, COMPASS, Delpor, Eisai, Enteris BioPharma, HLS Therapeutics, Idorsia, INmune Bio, Impel, Intra-Cellular Therapies, Janssen, Karuna, Lundbeck, Luye, Lyndra, MapLight, Marvin, MedAvante-ProPhase, Merck, Mitsubishi-Tanabe, Neumora, Neurocrine, Neurelis, Noema, Novartis, Noven, Otsuka, Ovid, Praxis, Recordati, Relmada, Reviva, Sage, Sumitomo/Sunovion, Supernus, Teva, University of Arizona, Vanda, and Wells Fargo, and one-off ad hoc consulting for individuals/entities conducting marketing, commercial, or scientific scoping research; served as a speaker for AbbVie/Allergan, Acadia, Alkermes, Angelini, Axsome, BioXcel, Eisai, Idorsia, Intra-Cellular Therapies, Janssen, Lundbeck, Neurocrine, Noven, Otsuka, Recordati, Sage, Sunovion, Takeda, and Teva; and performed CME activities organized by medical education companies such as Medscape, NACCME, NEI, and Vindico and universities and professional organizations/societies; owns stocks (small number of shares of common stock) in Bristol-Myers Squibb, Eli Lilly, Johnson & Johnson, Merck, and Pfizer purchased >10 years ago; has stock options in Reviva; and earns royalties/publishing income from Taylor & Francis (Editor-in-Chief, Current Medical Research and Opinion, 2022-present), Wiley (Editor-in-Chief, International Journal of Clinical Practice, through end 2019), UpToDate (reviewer), Springer Healthcare (book), and Elsevier (Topic Editor, Psychiatry, Clinical Therapeutics). Dr. Castelli and Dr. Komaroff received non-financial support from Hisamitsu Pharmaceutical Co, Inc., during the conduct of the study and received personal fees from Noven Pharmaceuticals, Inc. as employees, outside the submitted work. Mrs. Hasebe and Dr. Terahara received non-financial support from Hisamitsu Pharmaceutical Co, Inc. and received personal fees from Hisamitsu Pharmaceutical Co, Inc., outside the submitted work. Dr. Faden served in a consultancy/advisory role with and received grant support from BioXcel Therapeutics. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was funded by Hisamitsu Pharmaceutical Co, Inc. Although personnel at Hisamitsu Pharmaceutical Co, Inc. reviewed the manuscript, final approval for the decision to submit the manuscript was the sole decision of the authors.