Substance Spotlight: Nicotine & Tobacco — The Vaping Cessation Gap and the Drug That Could Fill It

Day 148 of 2026 · Substance Spotlight · Nicotine & Tobacco

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Nicotine is the most widely used addictive substance in the United States. Approximately 28 million Americans still smoke cigarettes, and a new generation — disproportionately young — has adopted e-cigarettes and vaping as their delivery method. The shift is not neutral: while vaping is less harmful than combustible tobacco, nicotine dependence is nicotine dependence, and millions of people who vape want to stop and cannot.

The treatment landscape for nicotine has not changed substantially in nearly two decades. Varenicline (Chantix), approved in 2006, remains the most effective pharmacological option. Nicotine replacement therapy predates the internet. Bupropion has modest efficacy. For the vaping-dependent population — whose nicotine exposure patterns differ from combustible smokers and who are often younger and differently motivated — none of these options was specifically tested.

That gap is about to close.

Cytisinicline: The Plant-Derived Contender

Cytisinicline is a partial nicotine receptor agonist — the same mechanism as varenicline — derived from laburnum plant seeds and used for decades as a smoking cessation aid in Eastern Europe, where it is sold as Tabex. It has never been approved by the FDA.

On June 20, 2026, the FDA’s Prescription Drug User Fee Act (PDUFA) date arrives for Achieve Life Sciences’ New Drug Application. If approved, cytisinicline would be the first new smoking cessation medication approved in the United States in nearly 20 years.

The clinical case is substantial:

• Phase 3 trials (ORCA-2 and ORCA-3) demonstrated significantly higher continuous abstinence rates compared to placebo at 12 and 24 weeks
• ICER’s independent cost-effectiveness analysis (February 2026) found cytisinicline’s efficacy “similar to varenicline” with a favorable safety profile
• FDA granted Breakthrough Therapy Designation for both smoking cessation and vaping cessation indications
• The FDA also granted a Commissioner’s National Priority Voucher for the vaping cessation indication — a signal of regulatory urgency

The Vaping Cessation Data

No currently FDA-approved medication was tested specifically for e-cigarette cessation. Cytisinicline fills this gap directly. In the Phase 2 ORCA-V1 trial, participants treated with cytisinicline were 2.6 times more likely to quit using nicotine e-cigarettes or vapes compared to placebo — a clinically meaningful effect size in a population with no approved pharmacological options.

This matters especially for people in recovery from other substances. Nicotine use is exceptionally common among people with SUD — estimates range from 60–90% — and continued smoking is associated with worse recovery outcomes and reduced life expectancy. A new, accessible, evidence-based option for nicotine cessation that works for vapers as well as smokers expands the toolbox for the whole recovery ecosystem.

Where the Field Disagrees

Not everyone is certain cytisinicline adds meaningfully over available treatments. ICER’s analysis noted “uncertainty in estimates” when comparing cytisinicline to varenicline — the two drugs appear similarly effective, which raises the question of whether a new branded prescription medication at a higher price point adds value over a generic. Varenicline is now available as generic vareniclcine at lower cost, and cytisinicline will launch as a branded drug given Achieve Life Sciences’ formulation patents.

The vaping-cessation data is also preliminary. The ORCA-V1 trial was Phase 2; Phase 3 data for this specific indication is not yet available. The FDA’s Breakthrough Therapy and Priority Voucher designations accelerate the review, but approval for vaping cessation may come as a supplemental indication after the primary smoking cessation approval.

Recent Developments Worth Watching

• March 2026: Achieve presented data from its ORCA-OL open-label extension at the Society for Research on Nicotine and Tobacco (SRNT), showing sustained cessation in smokers with extensive prior treatment exposure — the group most likely to have tried and failed varenicline.
• 52-week safety data: Achieve also presented safety findings from 52 weeks of continuous cytisinicline treatment, finding no new safety signals — important for a medication that may be used for extended periods.

Resources for People in Recovery

Nicotine dependence is a substance use disorder. It is treatable, and treating it matters for long-term recovery from all substances. Current options:

• Nicotine replacement therapy (NRT): Patches, gum, lozenges, nasal spray, inhaler — all available without prescription
• Varenicline (generic): Prescription required; most effective currently approved option
• Bupropion: Prescription required; modest efficacy
• Behavioral support: Quitlines (1-800-QUIT-NOW), text programs (text QUIT to 47848)
• Cytisinicline: Watch for FDA decision June 20, 2026

If you or someone in your life is working toward recovery and also uses nicotine, Rize’s care coordinators can help connect you with programs that address nicotine as part of a comprehensive recovery plan. Get started →

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