Nicotine Conjugate Vaccine for Smoking Cessation

Safety

The 3′-AmNic-rEPA vaccine produces antibodies that are highly specific for nicotine, demonstrating excellent discrimination between nicotine and other receptors, ligands, or neurotransmitters in the body. Antibodies from the vaccine remain in the peripheral circulation, limiting central nervous system adverse effects. Data from clinical trials indicate that the most common adverse effects from the 3′-AmNic-rEPA vaccine are mild localized reactions including ache and tenderness. Systemic reactions such as headache, myalgia, and malaise have been reported in vaccinated subjects. Local reactions were found to resolve 1–2 days after vaccination, and systemic reactions resolved on average in 1.5–3 days.^[14] Development of type 3 immune-complex hypersensitivity reactions have not been observed in clinical trials. Findings of herpes zoster in a small percentage of patients from a phase II trial will require further study.

An early trial with the nicotine vaccine demonstrated that over 40% of those receiving the active vaccine experienced weight gain compared with 0% in the placebo group.^[19] This was a small trial with only 30 subjects, and the authors cautioned that their findings should be considered preliminary. Weight gain has not been reported as a common adverse effect in other trials with the 3′-AmNic-rEPA vaccine. A trial involving another nicotine vaccine showed a nonsignificant difference in weight gain compared with placebo (10.5% vs 11.6%; odds ratio 0.9, 95% CI 0.4–1.8).^[23] Weight gain is a common concern for individuals quitting smoking, and data would indicate that the 3′-AmNic-rEPA vaccine does not have a significant impact on this unwanted adverse effect.

Drug Interactions

To our knowledge, no formal drug interaction studies have been performed with the 3′-AmNic-rEPA vaccine. Individuals taking corticosteroids and immunosuppressive agents were excluded from clinical trials as these agents may interfere with the efficacy of the vaccine. Because the vaccine is administered as an intramuscular injection, minimal effects on the hepatic cytochrome P450 system are expected. Caution should be used when administering intramuscular injections to patients receiving anticoagulation therapy or individuals with thrombocytopenia because of the potential for bleeding.

Cite this: Nicotine Conjugate Vaccine as a Novel Approach to Smoking Cessation - Medscape - Jul 01, 2011.

Table 1. Summary of Clinical Trials of the 3′-AmNic-rEPA Vaccine
Study Design, Duration	Study Population	Intervention	Primary Outcome	Results	Adverse Effects
Phase I–II, 38 wks19	Healthy men and women aged 24–60 yrs (n=30)	3′-AmNic-rEPA 100 μg i.m. or placebo given at baseline, 2 wks, 1 mo, and 6 mo	Immunogenicity and safety of multiple 100-μg doses of vaccine	Peak NSA level of 13.3 μg/ml in smokers and 4.4 μg/ml in nonsmokers achieved 1 wk after fourth injection in the vaccine group	Local: tenderness, ache, swelling, or induration at injection site Systemic: muscle ache, headache, bad taste, weight gain, general discomfort
Phase II, 38 wks^[14]	Men and women aged ≥ 18 yrs who smoked ≥ 15 cigarettes/day (n=68)	3′-AmNic-rEPA 50, 100, or 200 μg i.m. or placebo given at baseline and at 28, 56, and 182 days	Immunogenicity and safety of increasing doses of vaccine	Peak NSA level > 30 μg/ml 2 wks after third injection of 200 μg of vaccine; 30-day continuous smoking abstinence rate of 37.5% in abstinence rate of 37.5% in 200-μg vaccine group vs 8.7% in placebo group (not a primary end point)	Local: tenderness and ache at injection site Systemic: malaise, cough, headache, myalgias, upper respiratory infection, nasopharyngitis, myalgias
Phase IIb, 52 wks¹⁸	Men and women aged ≥ 18 yrs who smoked ≥ 15 cigarettes/day (n=301)	Group 1: 3′-AmNic-rEPA 200 or 400 μg i.m. or placebo given at baseline and at 6, 12, and 26 wks Group 2: 3′-AmNic-rEPA 200 or 400 μg i.m. or placebo given at baseline and at 4, 8, 16, and 26 wks	Continuous smoking abstinence rate from beginning of study wk 19 to end of study wk 26	High NSA responders achieved significantly greater 8-wk continuous abstinence rate compared with those in placebo group (24.6% vs 12%, p=0.024)	Local: tenderness and ache at injection site Systemic: malaise, headache, and myalgias
Two phase III (ongoing), 52 wks each^{20, 21}	Men and women aged 18–65 yrs who smoke ≥ 10 cigarettes/day (n=1000 in each trial)	3′-AmNic-rEPA 400 μg i.m. or placebo once/mo for 6 mo	Smoking abstinence at 12 mo	Not available	Not available

NSA = nicotine-specific antibody.

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