NicVAX

NicVAX is a nicotine conjugate vaccine intended to reduce or eliminate physical addiction to nicotine. According to the U.S. National Institute on Drug Abuse, NicVAX can potentially be used to inoculate against addiction.^[1] This proprietary vaccine is being developed by Nabi Biopharmaceuticals^[2] of Rockville, MD. with the support from the U.S. National Institute on Drug Abuse. NicVAX consists of the hapten 3'-aminomethylnicotine which has been conjugated (attached) to Pseudomonas aeruginosa exoprotein A. ^[3]

Nicotine is a small molecule that upon inhalation into the lungs quickly passes into the bloodstream and subsequently reaches the brain by crossing the blood-brain barrier. Once in the brain, the nicotine binds to specific nicotine receptors resulting in the release of stimulants, such as dopamine, a chemical linked to pleasure and to addiction. NicVAX is designed to stimulate the immune system to produce antibodies that bind to nicotine in the bloodstream and prevent it from crossing the blood-brain barrier and entering the brain. With a reduced amount of nicotine reaching the brain, fewer stimulants are released and the pleasurable, positive-reinforcing effects of nicotine are diminished, thereby making it easier to quit smoking. Pre-clinical studies with NicVAX have shown that vaccination prevents nicotine from reaching the brain and blocks the effects of nicotine, including effects that can lead to addiction or can reinforce and maintain addiction, in animals. NicVAX, in combination with quit-counseling, has been clinically demonstrated in smokers, who sincerely want to quit, having a better chance of breaking their smoking addiction.

NicVAX is still under development; a phase IIB proof-of-concept study was completed in November 2007. Nabi issued a press release^[4] in November 2007 indicating that phase IIB testing was a success, showing statistically significant rates of smoking cessation and continuous long-term smoking abstinence during the trial period.^[5][6]

Nabi Biopharmaceuticals initiated two Phase III trials of NicVAX^[7]. The first trial started in November 2009 and the second in March 2010. Nabi issued press releases^[8][9] announcing the start of these trials. The trials are being conducted in locations throughout the United States.^[10][11]

Administration and effects

NicVAX is administered via an injection into the arm; the 3'-aminomethylnicotine molecule found in the vaccine^[3] instigates an immune response in which 'nicotine' antibodies are created. The antibodies bind to nicotine molecules, causing the merged molecules to be too large to enter the brain; this prevents nicotine from being able to affect the body. The idea behind the drug is that since often even a single cigarette can deliver enough nicotine to the brain to reinstate the addiction, blocking the entry of nicotine into the brain might prevent this renewed dependence.^[12] This treatment works for nicotine addiction from any source.^[13] Clinical Pharmacology & Therapeutics considers this method "attractive," since the antibody does not enter the brain; as a result, side effects on the central nervous system are not expected. Additionally, the antibodies produced bond only with nicotine.^[3]

However, while this drug may curtail addiction, it does not prevent psychological cravings; in fact, a user could potentially smoke heavily to compensate for the nullifying effects of NicVAX.^[13] However, a study performed indicated that this did not happen among the test subjects.^[14]

Studies

Initial tests, involving injections of nicotine-specific immunoglobulin G into laboratory rats in the early 2000s, resulted in nicotine levels in the brain cut by up to 65%.^[3]

A study performed in 2005 for 38 weeks by the University of Minnesota Cancer Center's Transdisciplinary Tobacco Use Research Center and published in Clinical Pharmacology & Therapeutics, involved 68 smokers, none of whom had known health problems or intended to quit smoking in the next month. Subjects were not instructed to quit smoking during the course of the study. The test subjects were injected four times throughout the trial: when it began, and after four, eight and 26 weeks with either one of three dosages of NicVAX or a placebo. At the conclusion of the study, it was concluded that NicVAX was "safe and well-tolerated", with side effects including headaches, colds, and upper respiratory tract infections. While most of the test subjects continued to smoke, six people from the high dosage group, one person from the medium dosage group, no one from the low dosage group, and two people from the placebo group quit smoking. They did not start again for at least thirty days.^[14]

In the Phase IIb trial, a statistically significant number of patients with a high anti-nicotine antibody response met the primary endpoint of eight weeks of continuous abstinence between weeks 19-26. The top 30% of antibody responders (61 of the total 201 patients receiving drug) were examined in detail. A statistically significant number of these patients, (24.6%; p=0.04) showed continuous abstinence between weeks 19-26 compared to only 13.0% for the 100 patients receiving placebo. The quit rate of those patients who did not have a high antibody response was not statistically significant from placebo. The trial enrolled a total of 301 heavy smokers who smoked an average of 24 cigarettes per day prior to enrollment.^[15]

In July 2011 the first of two planned phase III trials for NicVAX failed [1], sending the market capitalization of NABI Biopharmaceuticals to below the value of its cash holdings.

References

1. ^ Barbara Shine (October 2000). "Nicotine Vaccine Moves Toward Clinical Trials". National Institute on Drug Abuse. Archived from the original on 2006-08-10. http://web.archive.org/web/20060810101935/http://www.drugabuse.gov/NIDA_Notes/NNVol15N5/Vaccine.html. Retrieved 2006-09-19. 
2. ^ "Nabi Biopharmaceuticals Website". http://www.nabi.com. 
3. ^ ^{a b c d} Hatsukami, DK; Rennard S, Jorenby D, Fiore M, Koopmeiners J, de Vos A, Horwith G, Pentel PR (2005). "Safety and immunogenicity of a nicotine conjugate vaccine in current smokers". Clinical Pharmacology & Therapeutics 78 (5): 456–467. doi:10.1016/j.clpt.2005.08.007. PMID 16321612. 
4. ^ "Nabi Biopharmaceuticals Announces Successful Completion of NicVAX(R) Phase 2b Trial; Drug Shows Statistically Significant Rates of Smoking Cessation and Continuous Long-Term Smoking Abstinence at 12 Months". Nabi Biopharmaceuticals. November 7, 2007. http://phx.corporate-ir.net/phoenix.zhtml?c=100445&p=irol-newsArticle&ID=1074098&highlight=. 
5. ^ Thomas E. Rathjen (2006-10-12). "Nabi Biopharmaceuticals Completes Enrollment in NicVAX Phase IIB 'Proof-of-Concept' Clinical Trial". Nabi Biopharmeceuticals. http://phx.corporate-ir.net/phoenix.zhtml?c=100445&p=irol-newsArticle&ID=915344&highlight=. Retrieved 2006-12-23. 
6. ^ name="20071107-pressrelease"
7. ^ http://behavioralhealthcentral.com/index.php/20091116133990/Latest-News/price-of-not-smoking-500m-nabi-gsk-in-nicvax-partnership.html
8. ^ "Nabi Biopharmaceuticals Initiates Pivotal Phase III Study for NicVAX as an Aid to Smoking Cessation and Long-term Abstinence". Nabi Biopharmaceuticals. November 3, 2009. http://phx.corporate-ir.net/phoenix.zhtml?c=100445&p=irol-newsArticle&ID=1350155&highlight=. 
9. ^ "Nabi Biopharmaceuticals Initiates Second Phase III Study for NicVAX as an Aid to Smoking Cessation and Long-term Abstinence". Nabi Biopharmaceuticals. March 17, 2010. http://phx.corporate-ir.net/phoenix.zhtml?c=100445&p=irol-newsArticle&ID=1403265&highlight. 
10. ^ "NicVAX/Placebo as and Aid to Smoking Cessation". ClinicalTrials.gov. February 2, 2009. http://www.clinicaltrials.gov/ct2/show/NCT00836199?term=nicvax&rank=2. 
11. ^ "A Second Study of NicVAX/Placebo as and Aid to Smoking Cessation". ClinicalTrials.gov. March 17, 2010. http://www.clinicaltrials.gov/ct2/show/NCT01102114?term=nicvax&rank=1. 
12. ^ Maurer, P; Jennings GT, Willers J, Rohner F, Lindman Y, Roubicek K, Renner WA, Muller P, Bachmann MF (2005). "A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity" (abstract page). European Journal of Immunology 35 (7): 2031–2040. doi:10.1002/eji.200526285. PMID 15971275. 
13. ^ ^{a b} Joseph Wang (August 17, 2000). "Is a Nicotine Vaccine the Magic Bullet for Smoking Cessation?". Health Law & Policy Institute, University of Houston. http://www.law.uh.edu/healthlaw/perspectives/PublicHealth/000817Nicotine.html. Retrieved 2006-09-19. 
14. ^ ^{a b} Miranda Hitti (November 29, 2005). "Nicotine Vaccine Shows Early Promise". Medscape. http://www.medscape.com/viewarticle/518161. Retrieved 2006-09-19. ^{[dead link]}
15. ^ "Nabi Biopharmaceuticals Announces Positive Results of Phase IIb Trial of NicVAX". Nabi Biopharmaceuticals. May 2, 2007. http://phx.corporate-ir.net/phoenix.zhtml?c=100445&p=irol-newsArticle&ID=994369&highlight=.