Immunogenicity and smoking-cessation outcomes for a novel nicotine immunotherapeutic

Abstract

NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.

Trial registration: ClinicalTrials.gov NCT00318383 NCT00598325.

Conflict of interest statement

Conflict of interest/Disclosure

Ms. Akhavain, and Drs. Fahim, Kessler, Kalnik and Niknian are employees of Nabi Biopharmaceuticals and have received salary support, stock and options. All other authors were investigators on the clinical trial funded by NIDA and by Nabi Biopharmaceuticals and some served on an advisory panel. Other disclosures include the following: Dr. Douglas Jorenby has received research support from Pfizer. Dr. David Gonzales has received grant/research support from Pfizer, Addex Pharmaceuticals, Sanofi-Aventis and GlaxoSmithKline; consulting fees and honoraria from Pfizer, GlaxoSmithKline, and Evotech NeuroSciences; speakers fees from Pfizer; and owning five shares of Pfizer stock. Dr. Nancy Rigotti has received research grant support from Pfizer and is an unpaid consultant to Pfizer and Free & Clear. Dr. Elbert Glover has served as a speaker, consultant, grantee, provided advice or is on the advisory board/panel for Pfizer and served as a speaker for Nabi Biopharmaceuticals.

Figures

Figure 1

Study design. Arrows denote timing of vaccinations for Schedule 1 (Week 0, 6, 12 and 26) and Schedule 2 (Week 0, 4, 8, 16, and 26). Primary endpoint (percent of subjects abstinent Week 19–26) and secondary endpoint (percent of subjects abstinent Week 19–52 are shown. NV (3’AmNic-rEPA); PBS (Phosphate buffered saline); Alum (aluminum hydroxide adjuvant); TQD (Target quit date).

Figure 2

Subject disposition.

Figure 3

For the intent-to-treat population: (A) 7-day point prevalence abstinence rates for high antibody (top 30% AUC), low antibody (bottom 70% AUC) groups and placebo over the course of 52 weeks; (B) Percent abstinent for week 45–52 (8 week continuous abstinence) by AUC. AUC is displayed in 10th percentile point increments; (C) Time to 8-week of sustained abstinence prior to week 46 and continuous abstinence maintained through week 52, stratified by group with high antibody (top 30% AUC), low antibody (bottom 70% AUC) and placebo (dropouts censored at week 52).

Figure 4

(A) Median number of cigarettes per day, (B) CO levels and (C) geometric mean cotinine levels among those subjects not abstaining from cigarettes across those subjects with high antibody (top 30% AUC), low antibody (bottom 70% AUC) and placebo. Time on the x-axis is adjusted to align the target quit date between Schedule 1 and Schedule 2.

Figure 5

Geometric mean antibody concentrations (µg/mL) by treatment group.