NicVAX

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NicVAX is an experimental conjugate vaccine intended to reduce or eliminate physical dependence to nicotine. According to the U.S. National Institute of Drug Abuse, NicVAX can potentially be used to inoculate against nicotine 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 exotoxin A. [3]

Contents

Early trials of NicVax were promising; two successive phase III trials showed results no better than placebo, [4] [5] and a more recent study showed that the drug decreased subjects' cravings for cigarettes. [6]

Mechanism

Nicotine is a small molecule that, after inhalation into the lungs, quickly passes into the bloodstream, subsequently crossing the blood–brain barrier. Once in the brain, it binds to specific nicotine receptors, resulting in the release of neurotransmitters, such as dopamine and norepinephrine.

NicVAX is a relapse prevention therapy designed to stimulate the immune system to produce antibodies that bind to nicotine in the bloodstream and prevent and/or slow it from crossing the blood–brain barrier and entering the brain. With a reduced amount of nicotine reaching the brain, neurotransmitter release is greatly lessened and the pleasurable, positive-reinforcing effects of nicotine are diminished. Pre-clinical studies with the vaccine have shown that vaccination slows and decreases the amount of nicotine that reaches the brain and blocks the effects of nicotine, including effects that can reinforce and maintain addiction in animals. Therefore, if a recently quit tobacco smoker is vaccinated and has a tobacco cigarette after the immunization series is completed, the antibodies generated by the vaccine bind nicotine and alter its distribution into the brain. Because not enough nicotine enters the brain, addiction-relevant neural pathways are not activated. No pleasure is derived from the tobacco cigarette and the vaccinated subject does not relapse and begin smoking again.

NicVAX is administered by 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 nicotine-antibody complexes to be too large to enter the brain; this prevents nicotine from being able to affect addiction-relevant pathways in the brain. 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. [7] This treatment works for nicotine addiction from any source. [8] 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 minimal, if any. Additionally, the antibodies produced bind only to nicotine and not to nicotine metabolites or any similar endogenous structures such as acetylcholine. [3]

However, while this drug may curtail addiction, it does not prevent psychological cravings; a user could potentially smoke heavily to compensate for the nullifying effects of NicVAX. [8] However, a study performed indicated that this did not happen among the test subjects. [9]

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]

Phase II trials

An early study 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 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. [9] [10]

In a further 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. [11] Nabi issued a press release 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. [12] [10]

Phase III trials

Nabi Biopharmaceuticals conducted two Phase III trials of the drug. [13] The first started in November 2009 and the second in March 2010. Nabi issued press releases [14] [15] announcing the start of these trials.

In July 2011 it was announced that the first of two planned phase III trials for NicVAX failed, [4] sending the market capitalization of NABI Biopharmaceuticals to below the value of its cash holdings. In November 2011, NABI announced that NicVAX had failed the second phase III clinical trial, performing no better than a placebo. [5]

Related Research Articles

<span class="mw-page-title-main">Nicotine</span> Chemical stimulant produced by some plants

Nicotine is a naturally produced alkaloid in the nightshade family of plants and is widely used recreationally as a stimulant and anxiolytic. As a pharmaceutical drug, it is used for smoking cessation to relieve withdrawal symptoms. Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor subunits where it acts as a receptor antagonist.

<span class="mw-page-title-main">Smoking cessation</span> Process of discontinuing tobacco smoking

Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often makes the process of quitting difficult.

<span class="mw-page-title-main">Allen Carr</span> British author (1934–2006)

Allen John Carr was a British author of books about stopping smoking and other psychological dependencies including alcohol addiction.

<span class="mw-page-title-main">Nicotine replacement therapy</span> Treatment for tobacco use disorder

Nicotine replacement therapy (NRT) is a medically approved way to treat people with tobacco use disorder by taking nicotine through means other than tobacco. It is used to help with quitting smoking or stopping chewing tobacco. It increases the chance of quitting tobacco smoking by about 55%. Often it is used along with other behavioral techniques. NRT has also been used to treat ulcerative colitis. Types of NRT include the adhesive patch, chewing gum, lozenges, nose spray, and inhaler. The use of multiple types of NRT at a time may increase effectiveness.

Nicorette is the brand name of a number of products for nicotine replacement therapy (NRT) that contain nicotine polacrilex. Developed in the late 1970s in Sweden by AB Leo in the form of a chewing gum, Nicorette was the first nicotine replacement product on the market.

<span class="mw-page-title-main">Cytisine</span> Chemical compound

Cytisine, also known as baptitoxine, cytisinicline, or sophorine, is an alkaloid that occurs naturally in several plant genera, such as Laburnum and Cytisus of the family Fabaceae. It has been used medically to help with smoking cessation. Although widely used for smoking cessation in Eastern Europe, cytisine remains relatively unknown beyond it. However, it has been found effective in several randomized clinical trials, including some in the United States and a large one in New Zealand, and is being investigated in additional trials in the United States and a non-inferiority trial in Australia in which it is being compared head-to-head with the smoking cessation aid varenicline. It has also been used entheogenically via mescalbeans by some Native American groups, historically in the Rio Grande Valley predating even peyote.

<span class="mw-page-title-main">Varenicline</span> Nicotinic receptor agonist

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<span class="mw-page-title-main">Nicotine withdrawal</span> Process of withdrawing from nicotine addiction

Nicotine withdrawal is a group of symptoms that occur in the first few weeks after stopping or decreasing use of nicotine. Symptoms include intense cravings for nicotine, anger or irritability, anxiety, depression, impatience, trouble sleeping, restlessness, hunger or weight gain, and difficulty concentrating. Withdrawal symptoms make it harder to quit nicotine products, and most methods for quitting smoking involve reducing nicotine withdrawal. Quit smoking programs can make it easier to quit. Nicotine withdrawal is recognized in both the American Psychiatric Association Diagnostic and Statistical Manual and the WHO International Classification of Diseases.


Tobacco harm reduction (THR) is a public health strategy to lower the health risks to individuals and wider society associated with using tobacco products. It is an example of the concept of harm reduction, a strategy for dealing with the use of drugs. Tobacco smoking is widely acknowledged as a leading cause of illness and death, and reducing smoking is vital to public health.

<span class="mw-page-title-main">Electronic cigarette</span> Device that vaporizes a liquid nicotine solution for inhalation

An electronic cigarette (e-cigarette) or vape is a device that simulates tobacco smoking. It consists of an atomizer, a power source such as a battery, and a container such as a cartridge or tank filled with liquid. Instead of smoke, the user inhales vapor. As such, using an e-cigarette is often called "vaping". The atomizer is a heating element that vaporizes a liquid solution called e-liquid, which quickly cools into an aerosol of tiny droplets, vapor and air. E-cigarettes are activated by taking a puff or pressing a button. Some look like traditional cigarettes, and most kinds are reusable. The vapor mainly comprises propylene glycol and/or glycerin, usually with nicotine and flavoring. Its exact composition varies, and depends on several things including user behavior.

<span class="mw-page-title-main">Nicotine dependence</span> Chronic disease

Nicotine dependence is a state of dependence upon nicotine. Nicotine dependence is a chronic, relapsing disease defined as a compulsive craving to use the drug, despite social consequences, loss of control over drug intake, and emergence of withdrawal symptoms. Tolerance is another component of drug dependence. Nicotine dependence develops over time as a person continues to use nicotine. The most commonly used tobacco product is cigarettes, but all forms of tobacco use and e-cigarette use can cause dependence. Nicotine dependence is a serious public health problem because it leads to continued tobacco use, which is one of the leading preventable causes of death worldwide, causing more than 8 million deaths per year.

Nicotine Anonymous (NicA) is a twelve-step program founded in 1982 for people desiring to quit smoking and live free of nicotine. As of July 2017, there are over 700 face-to-face meetings in 32 countries worldwide with the majority of these meetings occurring in the United States, Iran, India, Canada, Brazil, the United Kingdom, Australia, Russia and in various online community and social media platforms.. NicA maintains that total abstinence from nicotine is necessary for recovery. NicA defines abstinence as “a state that begins when all use of nicotine ceases.

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Nicotine vaccine is a novel immunological strategy for treating nicotine addiction. Nicotine vaccine uses active immunization as the methodology to create polyclonal antibodies to the antigens, which is then used to treat drug abuse. The immune system is then able to identify nicotine as a foreign substance and initiate an immune reaction targeting the drug. As a result, the quantity of nicotine that enters the brain would decrease after receiving the vaccine. In preclinical studies, nicotine vaccines have demonstrated the ability to combat the negative effects of nicotine abuse, but none of the developed vaccines has been authorized for use in clinical trials as a smoking cessation strategy. Theoretically, the decrease of nicotine's rewarding effects should result in smoking cessation. Some companies have tested candidate vaccines in clinical trials, but evidence failed to show the adequate antibody responses or exhibit superior efficacy to factors concerning placebo.

References

  1. ↑ Barbara Shine (October 2000). "Nicotine Vaccine Moves Toward Clinical Trials". National Institute on Drug Abuse. Archived from iuu the original on 2006-08-10. Retrieved 2006-09-19.{{cite web}}: Check |url= value (help)
  2. ↑ "nabi - Promoting And Inspiring Happiness". 2018-09-01. Archived from the original on 2018-09-01. Retrieved 2023-10-01.
  3. 1 2 3 4 Hatsukami, Dorothy K.; 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. S2CID   1218556.
  4. 1 2 "Nabi Biopharmaceuticals Announces Results of First NicVAX(R) Phase III Clinical Trial". 2016-01-17. Archived from the original on 2016-01-17. Retrieved 2023-10-01.
  5. 1 2 "Nabi Biopharmaceuticals Announces Results of Second NicVAX(R) Phase III Clinical Trial". 2019-03-05. Archived from the original on 2019-03-05. Retrieved 2023-10-01.
  6. ↑ Esterlis, Irina (22 February 2013). "Effect of a Nicotine Vaccine on Nicotine Binding to β2*-Nicotinic Acetylcholine Receptors In Vivo in Human Tobacco Smokers". American Journal of Psychiatry. 170 (4): 399–407. doi:10.1176/appi.ajp.2012.12060793. PMC   3738000 . PMID   23429725.
  7. ↑ 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". European Journal of Immunology. 35 (7): 2031–2040. doi: 10.1002/eji.200526285 . PMID   15971275. S2CID   44994620.
  8. 1 2 Joseph Wang (August 17, 2000). "Is a Nicotine Vaccine the Magic Bullet for Smoking Cessation?". Health Law & Policy Institute, University of Houston. Retrieved 2006-09-19.
  9. 1 2 Miranda Hitti (November 29, 2005). "Nicotine Vaccine Shows Early Promise". Medscape. Archived from the original on October 7, 2007. Retrieved 2006-09-19.
  10. 1 2 "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.
  11. ↑ "Nabi Biopharmaceuticals Announces Positive Results of Phase IIb Trial of NicVAX". Nabi Biopharmaceuticals. May 2, 2007.
  12. ↑ Thomas E. Rathjen (2006-10-12). "Nabi Biopharmaceuticals Completes Enrollment in NicVAX Phase IIB 'Proof-of-Concept' Clinical Trial". Nabi Biopharmeceuticals. Retrieved 2006-12-23.
  13. ↑ "Price of Not Smoking - 0M; Nabi, GSK in NicVax Partnership | Latest News". Archived from the original on 2009-11-21. Retrieved 2009-11-28.
  14. ↑ "Nabi Biopharmaceuticals Initiates Pivotal Phase III Study for NicVAX as an Aid to Smoking Cessation and Long-term Abstinence". Nabi Biopharmaceuticals. November 3, 2009.
  15. ↑ "Nabi Biopharmaceuticals Initiates Second Phase III Study for NicVAX as an Aid to Smoking Cessation and Long-term Abstinence". Nabi Biopharmaceuticals. March 17, 2010.
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