Washington Editor

WASHINGTON - With $10 million in stimulus funds in hand, Nabi Biopharmaceuticals has started a 1,000-patient Phase III trial of NicVAX (nicotine conjugate vaccine), which is the first time a vaccine to treat nicotine addiction has made it to late-stage testing.

Because nicotine is a tiny molecule, the human immune system is not able to recognize it as a foreign substance, therefore allowing it to cross the blood-brain barrier unhindered, said Nabi CEO Raafat E. F. Fahim.

Once in the brain, nicotine binds to specific nicotine receptors, which results in the release of stimulants, such as dopamine, giving smokers and other nicotine product users a pleasurable sensation - the cause of addiction.

NicVAX is designed to stimulate the immune system to produce antibodies that bind to nicotine in the bloodstream, making the nicotine molecule too large to cross the blood-brain barrier and enter the brain, which ultimately prevents the pleasure that keeps people addicted to smoking and other nicotine use, Fahim told BioWorld Today.

"So in essence, after you produce the antibodies to the NicVAX, you sequester the nicotine from your smoking into the blood and away from the brain, so you break the addiction cycle," he said.

In contrast to nicotine replacement treatments, such as gums or patches, or smoking cessation pharmaceutical agents, such as Pfizer Inc.'s Chantix (varenicline), NicVAX does not enter the brain, and therefore, does not have the same adverse psychological effects, such as depression or suicidal ideation, associated with the other treatments, noted Jamie Biswas, chief of the Medication Research Grants Branch at the National Institute on Drug Abuse (NIDA), whose agency provided the $10 million grant to help fund Nabi's Phase III development program.

NicVAX, Biswas explained, is "very specific. It just goes in, grabs the nicotine, and then it is excreted after awhile. It has no effect on the brain at all. All that it is doing is preventing nicotine from entering the brain."

NicVAX, Nabi's lead investigational vaccine candidate, is a "homegrown" product, Fahim said.

"One of our scientists saw that it may be interesting to look at the addiction field and use the conjugate vaccine technology that we have developed to have a vaccine for addiction," he said. Nabi's Phase III study, the first of two, is a 1,000-patient multicenter, randomized, double-blind, placebo-controlled trial assessing the efficacy, immunogenicity and safety of NicVAX as an aid to smoking cessation.

The primary endpoint of the study is the abstinence rate at 12 months, which will be evaluated by several measures, including self-reported cigarette consumption and exhaled carbon dioxide.

Secondary endpoints include the abstinence rate at various time intervals, safety and immunogenicity, and the effect of NicVAX on withdrawal symptoms, cigarette consumption, smoking satisfaction and nicotine dependency.

Patients in the study, who must be current smokers with at least a 10-cigarette per day addiction, will receive six injections over six months, Fahim said. He noted that study participants must want to quit smoking.

"Smokers have to be motivated to stop," Fahim said. "We cannot get a smoker who is not interested in stopping, because that is not going to work," he contended.

The smokers also must be in "otherwise good health" outside of their addiction, Fahim added.

The company designed the study under a special protocol assessment agreement with the FDA, he noted.

Nabi expects to have results by the third quarter of 2011, Fahim said.

A vaccine that limits the ability of nicotine to enter the brain, and is effective for six to 12 months following vaccination, will give smokers a "fighting chance" to end the addiction or relapse that "plagues the great majority of smokers trying to quit," said NIDA Director Nora Volkow.

Biswas noted that the $10 million, which was part of the $10 billion awarded to the National Institutes of Health under the American Recovery and Reinvestment Act, is a continuation of the public-private partnership NIDA and Nabi started in 2001, when the agency first provided a grant to support some of the basic science that led to NicVAX.

The agency also had provided a $4.1 million grant to Nabi in 2005 to support earlier tests of NicVAX, Biswas said.

"We would really like to have more collaborations with businesses, not just small businesses, but big pharma, too, in terms of helping developing all kinds of treatments for substance-related disorders," she told BioWorld Today.

NIDA's support of the NicVAX program, Fahim said, has been "phenomenal."

He noted that in addition to the financial support the company has received, the agency's experts have been available to "bounce ideas off of and getting their views. They have been great supporters for us."

The initiation of the first-ever Phase III trial of an antinicotine vaccine, Fahim said, "shows that public-private partnerships actually work very well if it is done right."

The start of the Phase III NicVAX trial also puts Nabi squarely in the lead in the antinicotine vaccine space.

The second closest company is Zurich, Switzerland-based Cytos Biotechnology Ltd. and its partner Novartis AG, of Basel, Switzerland.

However, the firms reported in October that a Phase II trial of their product, NIC002, had failed to meet its primary endpoint of continuous smoking abstinence.

Novartis said it was continuing the study to collect more long-term data and would decide on the next steps once the scheduled 12-month duration of the trial is completed and all data have been analyzed.

Published: November 4, 2009