New Nicotine Vaccine (NicVAX)

John (Gold)
Joined: 18 Dec 2008, 23:57

09 Nov 2007, 20:14 #31

Keep in mind that there are at least two products here, NicVax and Ta Nic. The below article is about Ta Nic but both products seem to be working with the "higher dose" now. If true and producing just 16% smoking cessation at one year, that's 5 points less than varenicline (Chantix & Champix) at 21%.
But if interested in making semi-valid comparisons among products that have never actually gone head to head, it's critical to keep an eye on a few additional factors: (1) participant expectations going into the study: what did the informed consent process and risk explanations prior to randomization or study recruiting prepare smokers to expect? (2) the ease or difficulty of determining group assignment: could you tell that some amout of smoked nicotine was not arriving in the brain, was the expected dopamine "aaah" sensation significantly smaller than normal, or if in the placebo group were your "aaahs" the same as before and you simply kept smoking and never quit; and (3) education, counseling, study contacts (brief quitter pep rallies) and group support, each having their own effectiveness, independent of the products being evaluated. How much study contact was there, when was it received, and at the time received, what percentage of each group was still present and fully participating in the study; if one group was then substantially larger than the other, did these independent cessation factors influence that group's overall success rate to a greater degree?
The 26 provider counseling and/or support contacts in Pfizer's varenicline studies were very likely a record, the most ever in any quit smoking clinical trial. But I get the feeling that Ta Nic and Nic Vax were trying to stand more on their own with vastly less user contact. Still, as to blinding and expectations both the vaccines and varenicline present rather interesting issues.
In NRT trials, most of the active group (those receiving replacement nicotine) could sense some level of easing off of the underlying current of withdrawal anxieties which was most stable with the patch but more noticible with oral and nasal nicotine, which was often administered in reaction to urges and craves. The more times the smoker had previously tried to quit and experienced the onset of full blown withdrawal the more they would have come to recognize their withdrawal syndrome.
Varenicline is closer to the effects of nicotine, sitting upon and blocking the exact same acetylcholine receptors nicotine would have occupied, while causing 35 to 60% of the dopamine flow nicotine would have generated. After day 5 of using varenicline, when it gets up to therapeutic levels, some user emails to me have described smoking a cigarette as if smoking a carrot - it does absolutely nothing for you, as you don't get the normal and expected "aaah" sensation."
This is why any suggestion that varenicline trials were "blind" and users could not correctly guess their group assignment is likely the biggest hoax smoking cessation has "yet" seen. The pharmaceutical industry was allowed to get away with NRT studies not being blind and appears to have become embolden by it.
What Pfizer is not telling users is that some day soon they'll stop taking varenicline, the dopamine flow it generates will end, and that in clinical trials half who succeeded in using it for 12 weeks thereafter relapsed to smoking.
But turning to blinding in Nic Vax and Ta Nic trials, the active vaccine group had a bit different experience than with NRT or varenicline. Instead of a somewhat diminished withdrawal syndrome or having up to 60% of the dopamine flow that nicotine provided (and 24 hours a day), in theory, vaccine users experience full-blown nicotine withdrawal, as if a member of the placebo group in an NRT or varenicline study, but with one big difference, what would normally have been relapse via smoking nicotine did not cause a dopamine "aaah" explosion in the brain 10 seconds later. How could an event such as this go unnoticed by any nicotine addict? It doesn't.
As with varenicline I can't see how vaccine researchers can, with a straight face, proclaim these studies blind. As with varenicline, it is not a matter of "guessing" your study group assignment but actual knowledge that a foreign chemical is present in your body and that your normal smoking experience has been seriously altered.
As for placebo group blinding, it too is somewhat unique in that some degree of motivation to quit smoking was to flow from cigarettes not providing their normal effect - relief from the onset of early withdrawal. Again, it's hard to believe that most placebo group members wouldn't have known their assignment.
But knowing group assignment is not the end of the analysis as to whether or not the study's results are valid. The question becomes, did assignment awareness combine with expectations to influence the participant's actions? In other words, if you volunteered for a study after learning it involved testing of a new "medication" and that you could get a free 12 week supply of the "medication," how would you react to actual knowledge that you were in fact getting it, or that you were not getting it?
If assigned to the placebo group and either still smoking or enduring full blown nicotine withdrawal, would you have stuck around for 12 weeks, 6 months or a year and allowed researchers to toy with you? In the active group, if your expectations had been met and you could actually feel the medication producing a totally new or somewhat different cessation experience, would such knowledge have given you new hopes, extra resolve and had you staying around longer than you otherwise would have, to try even harder and actually return for the study's next scheduled visit?
My reason for writing the above is to try and aid you in seeing that things are not always as represented, that should you feel your resolve weakening, that all these news articles and advertisements about new magic cures will hopefully not play even a minor role in inviting relapse. For what we do know is that in all real world quitting method surveys these products have yet to perform better than uneducated and unsupported "one your own" quitting.
We've each now arrested our dependency and there is absolutely no guarantee that any of us could ever come this far and heal this much again. There's only one way to stay on this side of the bars while keeping our now arrested dependency on the other ... no nicotine today, Never Take Another Puff, Dip or Chew!
John (Gold x8)

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John (Gold)
Joined: 18 Dec 2008, 23:57

01 May 2008, 00:05 #32

Swedish anti-nicotine vaccine to be
tested in Nordic countries - AFP

April 30, 2008

An anti-nicotine vaccine will be tested on 400 people in the Nordic countries over the next year aimed at helping smokers kick the habit, the Karolinska Institute in Sweden said on Monday.

"A Swedish vaccine against nicotine will be tested on 400 people in three Nordic countries," the institute said in a statement.

Lena Wikingsson, head of Independent Pharmaceutica, which is running the experiment, told Swedish daily Svenska Dagbladet that people taking part in the study -- heavy smokers who would like to quit -- would be given counselling before they stop smoking and would be given a drug to help them quit.

They will then receive one injection a month for four months. Half of the participants will be given the vaccine and the other half a placebo.

They will be followed for a year to see whether they begin to smoke again, Wikingsson said.

The vaccine, called Niccine, has been developed over the course of 10 years by Swedish researchers at the Karolinska Institute, under the guidance of professor Torgny Svensson who founded Independent Pharmaceutica.

Niccine is supposed to help the immune system build antibodies against nicotine.

If a person who has taken the vaccine smokes a cigarette, the antibodies jump into action, latching onto the incoming nicotine and preventing it from reaching the reward system in the brain -- thereby stopping the smoker from getting the "kick" that makes smoking addictive.

One problem in developing nicotine vaccines is that the immune system doesn't react to normal nicotine.

In order to activate the immune system, the nicotine in the vaccine needs to be latched onto a "carrier" or "host" that stimulates the immune system to create as many antibodies as possible.

For the vaccine to be successful, a large number of antibodies must be created, and the carrier component is therefore the key part of Niccine, Wikingsson said.

"There are several possible applications if the vaccine proves to be effective," Wikingsson told Svenska Dagbladet.
Online story source link
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JohnPolito
Joined: 11 Nov 2008, 19:22

06 Feb 2011, 19:45 #33

70% of placebo quitters did
better than NicVax quitters
Each new smoking cessation study seemingly sinks the integrity of smoking cessation researchers even lower.  Is it fair to expect otherwise when the vast majority of researchers are financially beholden to the pharmaceutical industry for income?   Think about it, if truthful yet negative words, analysis or spin were to cost the industry millions or even billions in profits, what likelihood is there that that researcher would ever work for the industry again?  

Let me share the most recent example, a Phase II study published on January 26, 2011 on Nabi's new quit smoking vaccine, NicVax.  The study shares 6 and 12 month smoking cessation rates of quitters receiving 4 or 5 placebo injections sought over 6 months, to the rates generated by groups receiving 4 or 5 NicVax injections at two different dose levels ( 200ug or 400ug).

According to the paper, the way the vaccine works is that:   

"Nicotine conjugate vaccines stimulate the immune system to develop nicotine-specific antibodies (Abs) using an immunogen comprised of nicotine covalently linked to a larger carrier protein. Conceptually, the mechanism of action is antinicotine Abs binding to nicotine molecules, and the resulting complex is too large to cross the blood–brain barrier. With increasing Ab levels, more nicotine is captured and sequestered in the blood and prevented from entering the brain, leading to a lowering of the reinforcing effects of nicotine. "

Image

First, take a look at the official study abstract published in PubMed,  contrasting my above title to the language highlighted below in red.    










Immunogenicity and Smoking-Cessation
Outcomes for a Novel Nicotine Immunotherapeutic
Journal:  Clinical Pharmacology and Therapeutics. 2011 January 26.

Authors:  Hatsukami DK, Jorenby DE, Gonzales D, Rigotti NA, Glover ED, Oncken CA, Tashkin DP, Reus VI, Akhavain RC, Fahim RE, Kessler PD, Niknian M, Kalnik MW, Rennard SI.

Department of Psychiatry, University of Minnesota Tobacco Use Programs, Minneapolis, Minnesota, USA.

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.

PMID: 21270788 [PubMed - as supplied by publisher]

PubMed Link:  http://www.ncbi.nlm.nih.gov/pubmed/21270788


Is it fair to say that the study's authors wanted to leave us with the impression that the NicVac nicotine vaccine is a resounding success, actually doubling the placebo group's rate (24.6% at 6 months versus 12%)?  There's only one problem, the language  I've highlighted in blue above, that these were the results from the top 30% within the NicVax groups whose immune systems showed the greatest response in creating nicotine antibodies, regardless of the number of injections received (4 or 5), and regardless of dosage (200ug or 400ug).

The obvious question becomes, how did the far greater 70% who also received NicVax injections do?   Let me quote from the study:









 High-Ab responders to 3′AmNicrEPA were defined as the top 30% of responders by area under the curve (AUC) (0–26 weeks) and the low-Ab group as the bottom 70% of responders. 3′AmNic-rEPA recipients in the high-Ab group were significantly more likely to attain 8 weeks of continuous abstinence from smoking from weeks 19 through 26 than were those receiving placebo (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14–6.37). No significant differences in results were observed between the 3′AmNic-rEPA low-Ab group and the placebo group (9.3% vs. 12.0%, P = 0.46). As a secondary outcome, continuous abstinence rates (CAR) to 52 weeks were evaluated from weeks 19–52; these were significantly higher in the high-Ab group relative to the placebo group (19.7% vs. 10.0%, P = 0.044, OR = 2.64, 95% CI 1.03–6.79); in contrast, there was no significant difference in results between the low-Ab group and the placebo group (7.1% vs. 10.0%, P = 0.43).
Yes, you are reading that correctly.  Placebo group six month (26 week) quit smoking rates were actually higher than among the 70% of quitters whose immune systems generated the lowest antibody response,  generating a 12% six-month placebo quitting rate versus only 9.3% for those receiving NicVax.  Placebo won again at one year with a 10% quit smoking rate versus only 7.1% among 70% of NicVax quitters receiving 4 or 5 injections.

What's also troubling is that the study provides no discussion within the full-text of the study as to how to identify which smoker would be among the 30% whose immune system would generate sufficient nicotine antibodies so as to achieve results comparable to those shared in the study's abstract (summary).   It also fails to explain why the study's authors chose 30% instead of some other percentage.  Is it coincidental that they chose a cutoff that resulted in doubling  placebo group rates, the same "double your chances" marketing used for nicotine replacement products?

Also troubling is the fact that researchers failed to report on the validity and integrity of the study's blind.   I suspect that they either didn't conduct a blinding assessment or failed to report results because  they would have been compelled to tell us that among the placebo group that 3 to 4 times as many participants correctly guessed their randomized group assignment to placebo as would have guessed wrong. 

Truth is, placebo group expectations do not change simply because the active group is testing and using a new quitting product.  If an experienced quitter, they joined hoping to get the vaccine and see some difference in their withdrawal sydrome.   When it didn't happen, participants with lengthy quitting histories, who were experts at recognizing their withdrawal syndrome, grew frustrated.  How many dropping out, helping hand NicVax an unearned victory by default?  Would you have returned for 4 more injections of sugar water?  Neither did some of them, and all of these researchers know it.  

It's why medicalization of smoking cessation has brought decline in the U.S. smoking rate to a standstill (a steady 21% of U.S. adults have remained smokers during the past five years).  You see, out here in the real-world placebo isn't a real quitting method.  

What researchers need to do is stop offering study quitters the worst quitting method on earth (placebo) and begin pitting these products against real cold turkey quitters, quitters who fully expect to endure and move beyond withdrawal.  But that can't and won't happen.  Why?  Because while their products consistently prevail over placebo inside randomized clinal trials, cold turkey quitters have prevailed in nearly evry long-term real-world quitting method survey to date.   Honest quit smoking studies would cost the pharmaceutical industry billions in profits.

I want to share one last item from this NicVax study.  These are the names of the study authors:
Hatsukami DK, Jorenby DE, Gonzales D, Rigotti NA, Glover ED, Oncken CA, Tashkin DP, Reus VI, Akhavain RC, Fahim RE, Kessler PD, Niknian M, Kalnik MW, Rennard SI.

And what follows is the financial conflicts disclosure statement from the full-text of the study.  
Conflict of Interest

R.C.A., R.E.F.F., P.D.K., M.W.K., and M.N. are employees of Nabi Biopharmaceuticals and have received salary support, stock, and stock options. All other authors were investigators on the clinical trial funded by NIDA and by Nabi Biopharmaceuticals, and some served on an advisory panel. D.E.J. has received research support from Pfizer. D.G. owns shares of Pfizer and has received grant/research support from Pfizer, Addex Pharmaceuticals, Sanofi-Aventis, and GlaxoSmithKline; consulting fees and honoraria from Pfizer, GlaxoSmithKline, and Evotech NeuroSciences; and speaker fees from Pfizer. N.A.R. has received research grant support from Pfizer and is an unpaid consultant to Pfizer and Free & Clear. E.D.G. has received grants from and served as a speaker and consultant for Pfizer. He has also provided advice to or is on the advisory board/panel of Pfizer. He has also served as a speaker for Nabi Biopharmaceuticals. C.A.O. has received grant funding from Pfizer. S.I.R. has participated as a speaker in scientific meetings and courses under the sponsorship of AstraZeneca, GlaxoSmithKline, and Pfizer; has served as consultant for several pharmaceutical companies with relevance to the topics noted in this study (Almiral, Altana, Amersham, Array Biopharma, AstraZeneca, Aventis, Boehringer Ingelheim, Critical Therapeutics, GlaxoSmithKline, Globomax, Intermune, Merck, Novartis, Ono, Otsuka, Roche, Sanofi, Scios, Wyeth); serves on advisory boards of Altana and Pfizer; has been sponsored by GlaxoSmithKline to conduct several clinical trials and received laboratory support; has conducted clinical trials sponsored by Roche, Pfizer, Sanofi, and Novartis; has conducted both clinical trials and basic studies under the sponsorship of Centocor; and has conducted basic studies under the sponsorship of AstraZeneca. This paper was presented in part at the American Heart Association Scientific Sessions 2007, Orlando, FL, 7 November 2007

 
Today we have smokers risking serious adverse events with Chantix when statistically Chantix has failed to prevail in generating more quitters than the nicotine patch at either six months or one year, when Chantix has never gone head-to-head with cold turkey quitters, and when real-world quitters are not receiving the the record 25 counseling/support sessions received by study participants.  Frankly, to this day, no one on earth can tell us Chantix's worth as a stand-alone quitting aid when used without record levels of counseling and support. 

Imagine a depression medication's worth being evaluated while also receiving record levels of counseling and then being sold without it.  Consumer fraud calls that a bait and switch tactic, while the pharmaceutical industry calls it smart business.     

What next?  Now we wait for the Phase III Nabi "not-so-blind" clinical trials that are already underway and scheduled to be complete in early 2012.

If you've found this article and Freedom via a search engine we encourage you to stay, explore and read  as knowledge is power!   What you'll discover is that there was always only one rule that if followed provides a 100% guarantee of success .... no nicotine just one hour, challenge and day at a time!  Yes you can!

Breathe deep, hug hard, live long,

John (Gold x11)
Last edited by JohnPolito on 19 Jul 2011, 11:15, edited 4 times in total.
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JohnPolito
Joined: 11 Nov 2008, 19:22

19 Jul 2011, 11:14 #34

NicVax Nicotine Vaccine is Dead
The below breaking Bloomberg news on Nabi's NicVax vaccine's failure to show effectiveness against placebo injections suggests two things:  (1) millions of nicotine addicts are in need of a new "coming magic cure" justification for putting off quitting, and (2) the vaccine's defeat was likely significantly worse than reported.

Since 2004, contrived headlines such as  "Nicotine Vaccine the End of Tobacco Era"  have teased and coaxed smokers into justifying putting off quitting.  Seven additional years of tobacco toxins slowly destroying their lungs, clogging their arteries and eating away their brain, millions of nicotine addicts now need a new justification for delaying any attempt to save their life.  

What few appreciate is that lies about coming magic cures feed the biggest lie of all, that life without smoking nicotine would be horrible.  What few smokers understand is that nicotine addiction is a brain wanting disorder,  a mental illness and disease as real, permanent and gripping as alcoholism.  What most claimed by their addiction fail to discover while still time is "The Law of Addiction," why one is always too many and a thousand never enough.   

So why are the below results likely worse than reported?  Because the study also offered participants ongoing counseling and support which we know has its own proven effectiveness. 

So why did the placebo group do so poorly?  Because experienced quitters joined this study seeking a way to minimize the withdrawal syndrome they'd felt during prior attempts and instead things felt the same.  Contrary to quitting study assertions, for smokers with lengthy quitting histories placebo-controlled smoking cessation studies are not blind as they have become experts at knowing exactly how withdrawal feels. 

If you'd joined a six injection vaccine study that promised that smoked nicotine would no longer be able to cross your blood-brain barrier to satisfy the wanting within, would you have stuck around and endured five more injections if you felt nicotine fully satisfy your wanting, just as it had done thousands of times before?  Neither did they.  And their early surrender after recognition that they'd been assigned to receive sugar-water placebo injections made the vaccine look far superior to its real worth.   

If you are a smoker who has stumbled upon this article at Freedom, we hope and pray that you don't leave until you've read the most important quitting lesson of all, "The Law of Addiction."  We hope you'll bookmark  www.WhyQuit.com and return to spend a time exploring, that you'll watch our free quitting videos in Joel's Library, and that once ready for serious support you'll visit us again here at Freedom from Nicotine.   

Contrary to the message flowing from your hijacked brain dopamine pathways and the thousands of old nicotine replenishment memories they've helped record, coming home to the real you can be the most liberating and glorious journey you'll ever make!   Remember, there's just one rule to successful quitting ... just one puff spells defeat.   Just one rule ... no nicotine just one hour, challenge and day at a time!

Breathe deep, hug hard, live long,

John - Gold x12    

 

Nabi Shares Plunge After Smoke-Cessation
Drug Shown Ineffective in Study




Bloomberg - By Oliver Renick - Jul 18, 2011 1:03 PM ET
Nabi Biopharmaceuticals (NABI), the developer of a vaccine for nicotine addiction, plunged to a 13- year low in Nasdaq trading after the treatment for smoking cessation failed to show effectiveness.

Nabi, based in Rockville, Maryland, dropped $1.75, or 69 percent, to $1.75 at 12:53 p.m. New York time in Nasdaq Stock Market trading, after earlier declining to $1.55, the lowest price since October 1998.

The drug, NicVAX, is an experimental vaccine aimed at aiding smoking cessation and preventing relapses in recovering smokers. NicVAX didn’t help smokers quit in the first of two Phase 3 clinical trials designed to evaluate effectiveness, Nabi said today in a statement.

“NicVAX is dead as currently configured,” Jeffrey Cohen, senior analyst at CK Cooper & Co. in Irvine, California, said in an interview. “Nabi’s recovery is somewhat unrealistic.”

Cohen has a “buy” rating that is under review, he said. He doesn’t own the stock.

Subjects using NicVAX quit smoking at a similar rate of 11 percent compared with subjects who received a placebo treatment, the company said. The study was part of the last of three stages of clinical trials generally required for U.S. regulatory approval.

Nabi is currently conducting a second round of Phase 3 trials that will analyze today’s results, President and Chief Executive Officer Raafat Fahim said in a webcast.

“We hope that our analysis over the next little while will shed light on the reasons for such surprising results,” Fahim said. “The trial was very well conducted.”

Nabi formed an exclusive option and license agreement for NicVAX with London-based GlaxoSmithKline Plc (GSK) in March 2010 that entitled Nabi to receive $20 million upon the successful completion of Phase 3 trials and up to $460 million in potential option fees.

To contact the reporter on this story: Oliver Renick in New York at [url=mailto:orenick@bloomberg.net]orenick@bloomberg.net[/url]
©2011 BLOOMBERG L.P. ALL RIGHTS RESERVED.
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