June 2026: FDA Delays Approval of Achieve’s Cytisinicline Over Manufacturing Issues
The U.S. Food and Drug Administration (FDA) has declined to approve Achieve Life Sciences’s smoking cessation drug cytisinicline, issuing a Complete Response Letter that cites unresolved issues at a third-party manufacturing facility and incomplete product labeling. Importantly, the agency did not identify any concerns regarding the drug’s safety or clinical efficacy.
Cytisinicline is a plant-derived, non-nicotine medication that reduces nicotine cravings and withdrawal symptoms by partially activating nicotine receptors in the brain. The drug is intended to expand the limited range of prescription smoking cessation therapies currently available, which largely consist of varenicline (formerly marketed as Chantix/Champix), bupropion (Zyban), and nicotine replacement therapies such as patches, gums and lozenges.
Achieve said it had anticipated the regulatory delay after its former contract manufacturer received an unfavorable FDA inspection. The company has since transferred production to Adare Pharma Solutions and plans to resubmit its application in the fourth quarter of 2026, with a potential FDA decision expected in the first half of 2027.
The setback is viewed as procedural rather than clinical. Phase 3 trials involving more than 1,500 participants demonstrated that cytisinicline significantly improved long-term smoking abstinence compared with placebo, with benefits lasting up to 24 weeks and no new safety concerns identified. The absence of efficacy or safety deficiencies supports the drug’s prospects for eventual approval.
October 2025: FDA grants priority review to Cytisinicline (Cytisine) for the treatment of nicotine vaping addiction
The U.S. Food and Drug Administration (FDA) announced the first-ever national priority voucher recipients under the Commissioner’s National Priority Voucher (CNPV) pilot program, including Achieve Life Sciences’ cytisinicline for the treatment of nicotine vaping addiction. The voucher recipients supposedly have a product with significant potential to address a major national priority, such as meeting a large unmet medical need, reducing downstream health care utilization, addressing a public health crisis, boosting domestic manufacturing, or increasing medication affordability with Most Favored Nation pricing.
Voucher recipients will receive a decision within 1-2 months following filing of a complete application. In addition, sponsors will receive enhanced communications with review staff throughout the development process prior to their final submission and during the review period. If necessary, FDA scientists reserve the right to extend the review time if an application is incomplete, there are manufacturing violations, or as they otherwise deem appropriate.
The new CNPV process accelerates the standard 10-12 month timeline by convening a multidisciplinary team of physicians and scientists for a team-based review, interacting frequently with the sponsor to clarify questions, and completing review of the application concurrently. Once all streamlined review steps are complete, the team will convene for a 1-day “tumor board style” meeting. Each drug review division within the FDA has been charged with nominating a product that they believe meets the stated national priority goals of the program. Sponsors can also apply and have their request reviewed by the designated review division.
July 2025: Cytisinicline (Cytisine) could soon be availble to American smokers and vapers
Achieve Life Sciences filed a New Drug Application (NDA) with the FDA on June 26, 2025, for cytisinicline, also known as baptitoxine, cytisine, or sophorine – an herbal, plant-based alkaloid aimed at treating nicotine dependence. The application is supported by two major Phase 3 trials, involving over 2,000 subjects, and long-term safety follow-up with more than 300 subjects using cytisine for at least six months. The clinical results are compelling: end-of-treatment nicotine cessation rates reached 14.8% (6-week group) and 30.3% (12-week group), compared to just 6.0% and 9.4% in the placebo arms. Overall, the data paint a strong risk‑benefit profile and position cytisinicline as a potential game‑changer in nicotine‑cessation therapeutics. These figures suggest cytisinicline could become the first new FDA‑approved smoking cessation aid in 20 years, addressing a major public‑health gap for 29 million American smokers and 17 million e‑cigarette users.
Cytisine has been used as a smoking cessation aid in Central & Eastern Europe since the 1960s. However, it is unavailable in most countries, including the US. Following the recent regulatory approval in the UK, Cytisine pills, referred as the “aspirin of smoking cessation” by some researchers, became available in the UK in January 2024 as a prescription-only medicine. Notably, cytisine was designated a “Breakthrough Therapy” by the FDA, especially with a view toward future vaping cessation indications.
November 2024: NHS England rolls out an improved stop-smoking pill
The National Health Service (NHS) announced the roll-out of an improved version of varenicline anti-smoking pill in England. NHS states that varenicline works as well as vapes to help quit smoking and is more effective aid than nicotine-replacement gum or patches. The daily pill is now set to be offered by the NHS as part of a drive to make more effective treatment options available1.
The drug works by reducing cravings for nicotine and blocking its effect on the brain, while also helping with withdrawal symptoms such as feeling irritable or having difficulty sleeping. When used alongside behavioural support, such as counselling, the treatment has been shown to help around one in four people (25%) to stop smoking for at least six months. It is estimated the use of varenicline on the NHS could help over 85,000 people try to stop smoking each year and its use over the next five years could prevent up to 9,500 smoking-related deaths, according to research by University College London.
The treatment is made available through a collaboration with pharmaceutical company Teva UK, who will provide a new generic version of the treatment to the NHS. A branded version of the smoking cessation pill (Champix) was previously used but was withdrawn in 2021 as a precaution after an impurity was discovered – however the relaunched generic product has now been approved as safe by the Medicines Health and Regulatory Authority (MHRA). Analysis by National Institute for Health and Care Excellence (NICE) in 2018 showed that for every £1 spent on the previous branded pill Champix alongside behavioural support, £1.65 was saved through preventing smoking-relating illnesses and hospitalisations – with the economic benefit set to be far greater with the cheaper generic version of the drug. Each year the NHS spends around £2.5 billion on treating health issues caused by smoking.
The other potential stop-smoking aid option under consideration is a cytisine pill that is currently under review by NICE.
July 2024
The World Health Organization (WHO) releases the first-ever clinical treatment guideline for tobacco cessation in adults and recommends a comprehensive set of interventions, including behavioral support, digital mediation and pharmacological treatments. According to the WHO, more than 750 million people (over 60% of the world’s 1.25 billion tobacco users) wish to quit, but 70% lack access to effective cessation services. This gap exists due to challenges faced by health systems, including resource limitations. WHO encourages health-care providers, policy-makers, and stakeholders to adopt and implement the guideline to promote tobacco cessation.
WHO recommends varenicline, bupropion, cytisine and Nicotine Replacement Therapy (NRT) as effective treatments for tobacco cessation. In 2023, WHO initiated a pre-qualification procedure for medicinal products to improve global access to recommended tobacco cessation medications. In April 2024, Kenvue’s nicotine gum and patch (sold under the brand name, Nicorette) became the first WHO pre-qualified NRT products.
In its announcement, the WHO spells out cigarettes, water-pipes, smokeless tobacco products, cigars, roll-your-own tobacco and heated tobacco products (HTPs) as the tobacco products to give up. However, e-cigarettes/vapes and nicotine pouches are not explicitly mentioned.
June 2024
Haleon sells its nicotine replacement therapy (NRT) business, outside the US, to a unit of India’s Dr. Reddy’s Laboratories for £500 million (~$633 million). The transaction includes an up-front payment of £458 million and is expected to close in Q4 2024. Haleon’s NRT business, powered by the Nicotinell brand, generated £217 million revenue is 2023. Nicotinell’s presence is primarily strong in nicotine lozenges, but the franschise also includes nicotine gums and patches. Nicotinell ranks among the top 15 over-the-counter products in Europe and is the second largest NRT brand in the world after Nicorette. Nicotinell is branded as Nicabate, Thrive or Habitrol in markets such as Australia, New Zealand and Canada. The divestment is expected to reduce Haleon’s FY24 net revenue and adjusted operating profit by about 0.5% and about 1%, respectively.
Haleon is a consumer health group formed as a result of the combination of Pfizer and GSK’s over-the-counter businesses in 2019 and was spun out of GSK in 2022. Among Haleon’s top products are the Sensodyne toothpaste brand, Centrum multivitamins and Tums antacids. Since then, the UK-based firm is re-engineering its portfolio to to lower debt and focus on growth areas such as non-prescription drugs, vitamins and oral care products. In January 2024, Haleon sold its ChapStick brand of products to Suave Brands Company for $430 million.
Dr. Reddy’s is one of India’s largest generic drugmakers while generating a significant share of its revenue from North America & Europe. Most recently, Dr. Reddy’s announced that it will form a joint venture with Nestle India to expand its presence in the consumer health sector (supplements and nutraceuticals).
January 2024
Cytisine is a natural ingredient of laburnum seeds and has been used as a smoking cessation aid in Central & Eastern Europe since the 1960s. However, it is unavailable in most countries, including the US. Following the recent regulatory approval in the UK, Consilient Health announced that Cytisine pills, referred as the “aspirin of smoking cessation” by some researchers, will be available in the UK as a prescription-only medicine from January 22, 2024. However, the high price tag (i.e. £115 for a 25-day course of 100 pills) could limit the use of the treatment.
Meanwhile, according to a recent research paper published in the Addiction Journal2, cytisine pills are as effective as varenicline (Champix) and possibly more effective than NRTs (patch & gum) – increasing the chances of success in quitting smoking by more than twofold compared to placebo (~6% quitting success without using any aid).
November 2023
Canadian anti-smoking advocates are calling on the federal government to restrict the sale of ZONNIC3 (recently approved by Health Canada) and seeking a moratorium on approval for any other nicotine pouches, unless they are made available only by prescription. The groups claim that
– while ZONNIC is marketed as a “nicotine replacement therapy” for adults, it is available for sale at convenience stores and gas stations with no legal restrictions on who can buy it
– ZONNIC’s social-media posts feature images of young people and highlight the product’s (youth appealing) flavors such as berry frost and tropic breeze.
In response, Imperial Tobacco Canada (part of BAT group) issued a statement4 noting that
– Despite the criticism from health groups, they believe that ZONNIC will help adult Canadians smokers quit and they support support regulations that limit the sale NRT category to adults 18 years old and over
– ZONNIC is licensed, regulated and advertised in the same way as any other smoking cessation product on the market
– There should be no reason why they should be singled out for adding another innovative choice to the market to help adult smokers quit.
Is this the best strategy for BAT to follow? In Canada, nicotine pouches (<4mg nicotine) are classified as “Natural and Non-prescription Health Product” and are marketed upon receiving a market authorization from Health Canada. BAT is using this rightful commercialization pathway to place ZONNIC on the market. Meanwhile, the regulatory status of nicotine pouches are unclear in many countries around the world and, in many cases, they are de-facto classified as consumer product – only subject to general product safety rules. Many countries (especially, the EU and EU states) are going through the process of deciding on the regulatory status of this emerging nicotine product category. Shifting the attention to Canada and putting the “Pharmaceutical/NRT” pathway as a viable/effective option to reach the intended audience (“smokers who want to stop smoking”) may not be in the best interest of tobacco companies at this stage. It won’t be easy to sell the idea that ZONNIC and VELO are different products based on the approval process and product placement/claims. If EU and other developed markets classify nicotine pouches as NRTs (limiting the distribution channels and access to the product, except for a handful of markets), we will slash the category’s global market potential for the tobacco companies by half (- the rest will mostly be the US, Scandinavia and UK).
Food for thought: maybe BAT is better off by being singled out from the Canadian NRT market until the regulatory status of nicotine pouches are clarified in key jurisdictions.
October 2023
Imperial Tobacco Canada (ITCAN), part of BAT group, will launch ZONNIC nicotine pouch as a smoking cessation product5 following the “license to sell” granted to BAT’s subsidiary, Nicoventures, by Health Canada. ZONNIC is the first nicotine pouch to receive Health Canada’s authorization. The licence application made to Health Canada included a pharmacokinetics study that assessed the bio-availability of nicotine in ZONNIC in comparison to other commercially available NRTs.
Niconovum, which sells own NRT products under the ZONNIC brand name in Nordics and also manufactures private-label NRT products, was acquired by Reynolds American (RAI) in 2009. Following the acquisition of RAI by BAT in 2017, Niconovum was brought under the umbrella of Nicoventures – a standalone company established by BAT in 2011 to exclusively focus on the development and commercialization of regulatory-approved, innovative nicotine products.
September 2023
After the disappearance of Champix (Pfizer) and Zyban (GSK) from the market, NRT is currently the only pharmacological treatment available in the UK. But, the trial data on cytisine puts a new treatment on the horizon6. Cytisine is a medicine that has been used as a smoking cessation aid in Central & Eastern Europe since the 1960s and could become the “aspirin of smoking cessation” according to researchers.
July 2023
Haleon is exploring the sale of Nicotinell (nicotine gum, patches and lozenges) as it seeks to offload non-core businesses7. Nicotinell attracts interest from both investment firms and consumer companies and is claimed to be worth as much as $800Mn.
Background:
UK National Health Service (NHS) lists 4 “Stop Smoking Treatments” on its website8.
(1) Nicotine replacement therapy (NRT): Reduces the withdrawal effects by providing a low level of nicotine. NRTs include nicotine patches, gums, inhalators, tablets/strips/lozenges as well as nasal & mouth sprays. Also available on prescription.
(2) Varenicline (Champix): Both reduces nicotine craving and blocks the rewarding/reinforcing effects of nicotine. Prescription only.
(3) Bupropion (Zyban): (Thought to) Affect the parts of the brain involved in addictive behavior. Prescription only.
(4) E-cigarettes: Not a pharmacological treatment. Nevertheless, NHS recommends e-cigarettes as a stop smoking aid – in this regard, NHS is pretty unique providing a positive recognition to the product. For instance, the US FDA recognizes only the first three products as the “Quit Smoking Treatments”9.
US FDA also provides an approved list of cessation medication – which is in line with the list of UK NHS (with the exception of e-cigarettes).
References:
- https://www.england.nhs.uk/2024/11/nhs-rolls-out-stop-smoking-%20pill-to-help-tens-of-thousands-quit ↩︎
- https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.16399 ↩︎
- Health Canada-approved Zonnic flavoured nicotine pouches target teens, say health experts – The Globe and Mail ↩︎
- Imperial_Tobacco_Canada_stands_by_ZONNIC_as_a_tobacco_harm_reduction_tool.pdf (imperialtobaccocanada.com) ↩︎
- Imperial Tobacco Canada: Zonnic Launch ↩︎
- https://pharmaceutical-journal.com/article/feature/filling-the-gap-in-smoking-cessation-therapies-a-race-to-a-smoke-free-2030 ↩︎
- https://www.bloomberg.com/news/articles/2023-07-03/advil-owner-haleon-said-to-mull-sale-of-nicotine-gum-business ↩︎
- https://www.nhs.uk/conditions/stop-smoking-treatments ↩︎
- https://www.fda.gov/consumers/consumer-updates/want-quit-smoking-fda-approved-and-fda-cleared-cessation-products-can-help ↩︎
