Achieve Life Sciences Announces Cytisinicline Phase 3 ORCA-3 Trial Publication on Smoking Cessation in JAMA Internal Medicine
Achieve Life Sciences (NASDAQ: ACHV) has published complete results of its ORCA-3 Phase 3 trial in JAMA Internal Medicine, evaluating cytisinicline for smoking cessation. The trial, involving 792 U.S. adults, demonstrated significant efficacy in both 6- and 12-week treatment durations.
The study showed that cytisinicline effectively increased quit rates and reduced nicotine cravings through 24 weeks. Trial participants averaged 53 years old, smoked 20 cigarettes daily, with a 36-year smoking history and four prior quit attempts. The drug's selective targeting of nicotine receptors resulted in better tolerability compared to existing treatments.
The company plans to submit a New Drug Application (NDA) to the FDA in June 2025.
Achieve Life Sciences (NASDAQ: ACHV) ha pubblicato i risultati completi del suo studio di Fase 3 ORCA-3 su JAMA Internal Medicine, valutando la citisiniclina per la cessazione del fumo. Lo studio, condotto su 792 adulti statunitensi, ha dimostrato un'efficacia significativa sia con trattamenti di 6 che di 12 settimane.
La ricerca ha evidenziato che la citisiniclina aumenta efficacemente i tassi di astinenza e riduce il desiderio di nicotina fino a 24 settimane. I partecipanti avevano in media 53 anni, fumavano 20 sigarette al giorno, con una storia di fumo di 36 anni e quattro tentativi precedenti di smettere. Il farmaco, agendo selettivamente sui recettori della nicotina, ha mostrato una migliore tollerabilità rispetto ai trattamenti attuali.
L'azienda prevede di presentare una domanda di Nuovo Farmaco (NDA) alla FDA a giugno 2025.
Achieve Life Sciences (NASDAQ: ACHV) ha publicado los resultados completos de su ensayo de Fase 3 ORCA-3 en JAMA Internal Medicine, evaluando citisiniclina para la cesación del tabaquismo. El estudio, que involucró a 792 adultos en EE. UU., demostró una eficacia significativa en tratamientos de 6 y 12 semanas.
El estudio mostró que la citisiniclina aumentó eficazmente las tasas de abandono y redujo los antojos de nicotina hasta 24 semanas. Los participantes tenían un promedio de 53 años, fumaban 20 cigarrillos diarios, con 36 años de historia de tabaquismo y cuatro intentos previos de dejar de fumar. El medicamento, al dirigirse selectivamente a los receptores de nicotina, presentó mejor tolerabilidad en comparación con los tratamientos existentes.
La compañía planea presentar una Solicitud de Nuevo Medicamento (NDA) a la FDA en junio de 2025.
Achieve Life Sciences (NASDAQ: ACHV)는 금연을 위한 시티시닐클린(cytisinicline)을 평가한 ORCA-3 3상 임상시험의 완전한 결과를 JAMA Internal Medicine에 발표했습니다. 미국 성인 792명을 대상으로 한 이번 시험은 6주 및 12주 치료 기간 모두에서 유의미한 효능을 입증했습니다.
연구 결과 시티시닐클린은 금연 성공률을 효과적으로 높이고 니코틴 갈망을 24주까지 줄이는 것으로 나타났습니다. 참가자들의 평균 연령은 53세였으며 하루 20개비의 담배를 피우고, 36년간 흡연해왔으며 4번의 금연 시도를 경험했습니다. 이 약물은 니코틴 수용체를 선택적으로 타겟팅하여 기존 치료제보다 내약성이 우수했습니다.
회사는 2025년 6월 FDA에 신약 승인 신청서(NDA)를 제출할 계획입니다.
Achieve Life Sciences (NASDAQ : ACHV) a publié les résultats complets de son essai de phase 3 ORCA-3 dans JAMA Internal Medicine, évaluant la cytisinicline pour l'arrêt du tabac. L'essai, impliquant 792 adultes américains, a démontré une efficacité significative pour des traitements de 6 et 12 semaines.
L'étude a montré que la cytisinicline augmentait efficacement les taux d'arrêt et réduisait les envies de nicotine jusqu'à 24 semaines. Les participants avaient en moyenne 53 ans, fumaient 20 cigarettes par jour, avec une histoire tabagique de 36 ans et quatre tentatives d'arrêt antérieures. Le médicament, ciblant sélectivement les récepteurs nicotiniques, a présenté une meilleure tolérance comparé aux traitements existants.
L'entreprise prévoit de soumettre une demande d'autorisation de mise sur le marché (NDA) à la FDA en juin 2025.
Achieve Life Sciences (NASDAQ: ACHV) hat die vollständigen Ergebnisse seiner ORCA-3 Phase-3-Studie in JAMA Internal Medicine veröffentlicht, in der Cytisiniclin zur Raucherentwöhnung untersucht wurde. Die Studie mit 792 erwachsenen US-Teilnehmern zeigte eine signifikante Wirksamkeit sowohl bei 6- als auch bei 12-wöchigen Behandlungszeiträumen.
Die Untersuchung ergab, dass Cytisiniclin die Abstinenzraten effektiv steigerte und das Nikotinverlangen bis zu 24 Wochen verringerte. Die Studienteilnehmer waren im Durchschnitt 53 Jahre alt, rauchten 20 Zigaretten täglich, hatten eine 36-jährige Rauchgeschichte und vier vorherige Entwöhnungsversuche. Das Medikament, das selektiv auf Nikotinrezeptoren wirkt, zeigte eine bessere Verträglichkeit im Vergleich zu bestehenden Behandlungen.
Das Unternehmen plant, im Juni 2025 einen Zulassungsantrag (NDA) bei der FDA einzureichen.
- Successful Phase 3 ORCA-3 trial results published in prestigious JAMA Internal Medicine
- Demonstrated significant efficacy in smoking cessation and craving reduction
- Superior tolerability profile compared to existing treatments
- Extended cessation benefits through 24 weeks
- NDA submission not planned until June 2025, indicating longer timeline to potential commercialization
Insights
Cytisinicline's successful Phase 3 results published in JAMA Internal Medicine strengthen Achieve's NDA submission planned for June 2025.
The publication of Achieve Life Sciences' Phase 3 ORCA-3 trial results in JAMA Internal Medicine marks a critical milestone for cytisinicline as a smoking cessation treatment. This prestigious journal publication adds substantial credibility to the data package and represents the second successful Phase 3 trial, significantly strengthening the regulatory submission.
The ORCA-3 data demonstrated that cytisinicline significantly increased quit rates compared to placebo at both 6-week and 12-week treatment durations, with benefits extending through 24 weeks. The drug's highly selective binding to nicotine receptors with minimal off-target activity appears to provide a favorable tolerability profile compared to existing options.
Most notably, the company has confirmed plans to submit its New Drug Application (NDA) to the FDA in June 2025, putting them on a clear regulatory timeline. The smoking cessation market remains underserved despite smoking being a leading preventable cause of death in the US.
The endorsement from Dr. Nancy Rigotti of Harvard Medical School adds further validation to cytisinicline's potential clinical value. The study population closely reflected real-world smokers with long smoking histories and multiple previous quit attempts, strengthening the applicability of these results to the broader smoking population.
Cytisinicline shows significant efficacy for smoking cessation with improved tolerability, addressing limitations of current treatments.
The ORCA-3 trial provides compelling evidence for cytisinicline's effectiveness in smoking cessation through a highly targeted mechanism that specifically binds to nicotine receptors. This selectivity is particularly noteworthy as it appears to minimize the off-target effects that often cause troublesome side effects with existing treatments like varenicline.
The study population included smokers with a median 36-year smoking history and four previous quit attempts, closely reflecting the challenging real-world smoking population that clinicians treat daily. Interestingly, less than half had previously tried varenicline, potentially due to its known adverse event profile.
Beyond just helping smokers quit, cytisinicline demonstrated meaningful reductions in nicotine cravings and decreased cotinine levels (a nicotine metabolite) even among participants who continued smoking. This suggests potential harm reduction benefits alongside cessation efficacy.
The sustained benefits through 24 weeks address one of the most significant challenges in smoking cessation—maintaining abstinence over time. The replication of positive results across two large Phase 3 trials provides confidence in cytisinicline's consistent efficacy profile.
With smoking remaining a leading preventable cause of death and current treatment options , cytisinicline could potentially fill a significant unmet need in addiction medicine if approved.
ORCA-3 Demonstrated a Significant Increase in Quitting and Reduction in Nicotine Cravings for Cytisinicline-Treated Participants Compared to Placebo
Cytisinicline New Drug Application (NDA) Submission to FDA Planned for June 2025
SEATTLE and VANCOUVER, British Columbia, April 21, 2025 (GLOBE NEWSWIRE) -- Achieve Life Sciences, Inc. (Nasdaq: ACHV), a late-stage specialty pharmaceutical company focused on the global development and commercialization of cytisinicline as a treatment of nicotine dependence for smoking cessation, today announced that complete trial results from its ORCA-3 were published in the Journal of the American Medical Association (JAMA) Internal Medicine. ORCA-3 was the second randomized, placebo-controlled Phase 3 clinical trial evaluating cytisinicline for smoking cessation in 792 U.S. adults. The authors concluded that ORCA-3 reaffirms cytisinicline’s efficacy and tolerability for smoking cessation in adult smokers at both 6- and 12-week treatment durations, including reduction in nicotine cravings and extended cessation benefits through 24 weeks.
In addition to previously reported topline results announced in May 2023, the published completed trial results provided further evidence of cytisinicline’s highly targeted effect on treating nicotine dependence by binding to specific nicotine receptors. These consistent results, now published from two large, randomized Phase 3 trials, demonstrated that cytisinicline significantly reduced nicotine cravings and increased the likelihood of quitting smoking. In clinical trials, cytisinicline was well tolerated, which is thought to be due to limited other off-target binding effects that can result in side effects known to be associated with currently available treatments.
Similar to the first Phase 3 trial, ORCA-3 participants had an average age of 53 years, smoked a median of 20 cigarettes per day at baseline, and had a median smoking history of 36 years with four prior quit attempts.
“Most people who smoke want to quit and it often takes multiple attempts to do so successfully. Our trial participants were no exception and had multiple previous quit attempts, although less than half had previously tried varenicline, possibly due to its well-known adverse event profile,” said Cindy Jacobs, MD, PhD, President and Chief Medical Officer of Achieve Life Sciences. “Cytisinicline is very selective in targeting only nicotine receptors and has shown limited binding to other off-target receptors that can cause side effects, like nausea and gastrointestinal disturbances. We believe this leads to a highly tolerable treatment with cytisinicline, as demonstrated in our clinical trial program.”
Results from the ORCA-3 study show that cytisinicline significantly increased the odds of smoking cessation compared to placebo. Cytisinicline also reduced nicotine craving which led to decreased nicotine intake, even among those who continued smoking, as evidenced by both lower craving scores and reduced cotinine levels, a well-known metabolite of nicotine.
“More deaths each year in the U.S. are attributed to cigarette smoking than to any other preventable cause, and our current smoking cessation treatment options are limited,” said Nancy Rigotti, MD, Professor of Medicine at Harvard Medical School, Director of Tobacco Research and Treatment Center, Massachusetts General Hospital, and ORCA Program Investigator. “The study findings published today suggest that cytisinicline, if approved by the FDA, could help many smokers to quit and reduce the smoking-related risks to their health.”
Achieve plans to submit the cytisinicline New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in June 2025.
About ORCA-3
The Phase 3 ORCA-3 trial evaluated 792 adults who smoked cigarettes daily and was conducted at 20 clinical trial locations in the U.S. The trial was initiated in January 2022 and completed enrollment in September 2022, with topline results reported in May 2023. ORCA-3 participants received 3mg cytisinicline dosed 3 times daily for either 6 or 12 weeks and were monitored through 24 weeks post randomization. The trial was blinded, placebo-controlled, and all subjects received behavioral support for the duration of the trial. The primary endpoint was biochemically verified continuous abstinence during the last four weeks of treatment. Secondary outcome measures assessed continued abstinence rates through 6 months from the start of study treatment. The full manuscript is published in Journal of the American Medical Association (JAMA) Internal Medicine.
About Achieve Life Sciences, Inc.
Achieve Life Sciences is a late-stage specialty pharmaceutical company committed to addressing the global smoking health and nicotine dependence epidemic through the development and commercialization of cytisinicline. The company has successfully completed two Phase 3 studies with cytisinicline for smoking cessation and one Phase 2 study with cytisinicline in vaping cessation. The company has fully enrolled its ongoing open-label safety study with cytisinicline and plans to submit its new drug application for smoking cessation in June 2025. Achieve has also conducted a successful end-of-Phase 2 meeting with the FDA for a future vaping indication.
About Cytisinicline
There are approximately 29 million adults who smoke combustible cigarettes.1 Tobacco use is currently the leading cause of preventable death that is responsible for more than eight million deaths worldwide and nearly half a million deaths in the United States annually.2,3 More than
In addition, there are over 11 million adults in the United States who use e-cigarettes, also known as vaping.4 In 2024, approximately 1.6 million middle and high school students in the United States reported using e-cigarettes.5 There are no FDA-approved treatments indicated specifically as an aid to nicotine e-cigarette cessation. Cytisinicline has been granted Breakthrough Therapy designation by the FDA to address this critical need.
Cytisinicline is a plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor. It is believed to aid in treating nicotine addiction for smoking and e-cigarette cessation by interacting with nicotine receptors in the brain, reducing the severity of nicotine craving symptoms, and reducing the reward and satisfaction associated with nicotine products. Cytisinicline is an investigational product candidate being developed for the treatment of nicotine addiction and has not been approved by the Food and Drug Administration for any indication in the United States.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the timing and nature of cytisinicline clinical development and regulatory review and approval, data results and commercialization activities, the potential market size for cytisinicline, the potential benefits, efficacy, safety and tolerability of cytisinicline, the development and effectiveness of new treatments, and the successful commercialization of cytisinicline. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Achieve may not actually achieve its plans or product development goals in a timely manner, if at all, or otherwise carry out its intentions or meet its expectations or projections disclosed in these forward-looking statements. These statements are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements, including, among others, the risk that cytisinicline may not demonstrate the hypothesized or expected benefits; the risk that Achieve may not be able to obtain additional financing to fund the development and commercialization of cytisinicline; the risk that cytisinicline will not receive regulatory approval in a timely manner or at all, or be successfully commercialized; the risk that new developments in the smoking and vaping cessation landscapes require changes in business strategy or clinical development plans; the risk that Achieve’s intellectual property may not be adequately protected; general business and economic conditions; risks related to the impact on our business of macroeconomic and geopolitical conditions, including fluctuating inflation, interest and tariff rates, volatility in the debt and equity markets, actual or perceived instability in the global banking system, global health crises and pandemics and geopolitical conflict and the other factors described in the risk factors set forth in Achieve’s filings with the Securities and Exchange Commission from time to time, including Achieve’s Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q. Achieve undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable.
Achieve Contact
Nicole Jones
ir@achievelifesciences.com
425-686-1510
References
1VanFrank B, Malarcher A, Cornelius ME, Schecter A, Jamal A, Tynan M. Adult Smoking Cessation — United States, 2022. MMWR Morb Mortal Wkly Rep 2024;73:633–641.
2World Health Organization. WHO Report on the Global Tobacco Epidemic, 2019. Geneva: World Health Organization, 2017.
3U.S. Department of Health and Human Services. The Health Consequences of Smoking – 50 Years of Progress. A Report of the Surgeon General, 2014.
4Cornelius ME, Loretan CG, Jamal A, et al. Tobacco Product Use Among Adults – United States, 2021. MMWR Morb Mortal Wkly Rep 2023;72:475–483.
5Jamal A, Park-Lee E, Birdsey J, et al. Tobacco Product Use Among Middle and High School Students — National Youth Tobacco Survey, United States, 2024. MMWR Morb Mortal Wkly Rep 2024;73:917–924.
FAQ
What were the key findings of ACHV's ORCA-3 Phase 3 trial for cytisinicline?
When will Achieve Life Sciences submit the cytisinicline NDA to the FDA?
How many participants were involved in the ORCA-3 smoking cessation trial?
What distinguishes cytisinicline from current smoking cessation treatments?
