X-22 is a kit containing very low nicotine (VLN) cigarettes going through the FDA-approval process as a prescription smoking cessation aid.

22nd Century believes X-22 facilitates quitting by satisfying smokers’ cravings for cigarettes while (i) greatly reducing nicotine exposure and nicotine dependence and (ii) extinguishing the association between the act of smoking and the expected delivery of nicotine. The therapy protocol allows the patient to smoke VLN cigarettes over a six-week treatment period to facilitate the goal of the patient quitting smoking following the treatment period.

Independent Studies Demonstrate VLN Cigarettes Can Increase Quit Rates

Independent studies on very low nicotine (VLN) cigarettes for smoking cessation have shown increased quit rates, whether VLN cigarettes were used alone or concurrently with nicotine replacement therapy (NRT), including the following 4 clinical trials (2019 total subjects):

1.   Clinical Trials Research Unit, The University of Auckland – Phase III – 1,410 subjects
2.   University of Minnesota Masonic Cancer Center – Phase II – 165 subjects
  • Hatsukami et al. 2010
  • VLN cigarette had significantly better results than FDA-approved nicotine lozenge and a reduced nicotine cigarette (6 times more nicotine than the VLN)
3.   Vector Tobacco
  • Becker et al. 2008
  • Reduced nicotine cigarettes for 6 weeks, including VLN cigarette for 2 weeks, before use of nicotine patch significantly increased quit rates over use of nicotine patch
  • 22nd Century has a right of reference to trial
4.   Roswell Park Cancer Institute
  • Rezaishiraz et al. 2007
  • Use of VLN cigarette before use of nicotine patch increased quit rates over use of reduced nicotine cigarette (containing 10 times more nicotine than the VLN) before nicotine patch

Results Pending – Two Completed Independent Clinical Trials

University of Minnesota Masonic Cancer Center – Phase II – 219 subjects
  • Follow-up study to Hatsukami et al. 2010
  • ClinicalTrials.gov Identifier:  NCT01050569
  • Evaluating quitting results of six-week treatment period among: (i) exclusive use of a VLN cigarette (a version of X-22 with slightly higher nicotine content provided by 22nd Century); (ii) 21-mg nicotine patch; and (iii) concurrent use of VLN cigarette and nicotine patch
  • Trial included a 6-month follow-up period
Queen Mary University of London, in collaboration with Pfizer – 200 subjects
  • ClinicalTrials.gov Identifier:  NCT01250301
  • Evaluating whether the use of a VLN cigarette (a version of X-22 with slightly higher nicotine content provided by 22nd Century) in combination with Chantix® (or NRT) increases quitting over use of Chantix (or NRT) alone
  • Chantix® is branded as Champix® outside the United States

In the University of Minnesota Phase II trial (Hatsukami et al. 2010), patients exclusively using a VLN cigarette containing 22nd Century’s VLN proprietary tobacco achieved a 43% quit rate (confirmed four-week continuous abstinence) as compared to a quit rate of 35% for the group exclusively using a FDA-approved 4 mg nicotine lozenge (Commit®) and a 21% quit rate for the group exclusively using a low nicotine cigarette. Smoking abstinence at the 6 week follow-up after the end of treatment was 47% for the VLN cigarette group, 37% for the nicotine lozenge group and 23% for the low nicotine cigarette group. Carbon monoxide (CO) levels in patients were tested at each clinic visit to verify smoking abstinence.  As an intent-to-treat clinical trial, subjects who dropped out were considered not abstinent or smoking.

The VLN cigarette was also associated with greater relief from withdrawal symptoms and craving of usual brand cigarettes than the 4 mg nicotine lozenge. In fact, cravings continued to decline for weeks after treatment as shown here:

22nd Century Sponsored Clinical Trial

22nd Century sponsored a Phase II-B clinical trial (238 subjects) under its own investigational new drug application cleared by the U.S. Food and Drug Administration (FDA) in July 2011.  The X-22 VLN cigarettes utilized in the Company’s trial had a nicotine content of less than half of the nicotine content of the VLN cigarettes utilized in the above six summarized clinical trials. Although there was no statistically significant difference in quit rates compared to the active control (a cigarette containing conventional nicotine levels), there was a significant reduction in smoking during the 6-week treatment period and post treatment from baseline. 22nd Century and independent researchers believe that the nicotine content of X-22 utilized in the Company’s Phase II-B trial was below a cessation effective threshold.  As was the case with independent clinical trials utilizing VLN cigarettes, there were no serious adverse events attributable to X-22 and the product was well tolerated.  Going forward all company-sponsored clinical trials will utilize VLN cigarettes with a relatively higher nicotine content.

Clinical Pathway to FDA Approval

22nd Century has licensed Hercules Pharmaceuticals LLC, its pharmaceutical subsidiary, exclusive worldwide rights to X-22.  Hercules Pharmaceuticals will evaluate results and data from recently completed independent clinical trials that utilized the Company’s VLN cigarette with a slightly higher nicotine content to determine which variables optimize quitting.  Upon completing analyses of these trials, the Company expects to conduct Phase III clinical trials.  Hercules Pharmaceuticals is currently identifying potential partners for the further development and worldwide commercialization of X-22.