Achieve Life Sciences Reaches Agreement with the FDA on Long-Term Cytisinicline Exposure Data Requirements for NDA Submission

Rhea-AI Summary

Achieve Life Sciences, Inc. announces FDA agreement on long-term safety data requirements for cytisinicline NDA submission, plans to initiate open-label exposure trial in Q2’24. Achieve also secures $124.2 million financing, including milestone-driven warrants.

Insights

Pharmaceutical Industry Analyst

The agreement between Achieve Life Sciences and the FDA regarding the long-term exposure data for cytisinicline is a strategic milestone for the company. The FDA's support for an NDA submission based on the Phase 3 trials indicates a positive regulatory environment for Achieve. The requirement for long-term safety data aligns with the FDA's stance on smoking cessation drugs, which are often used repeatedly or intermittently. The decision to conduct a single open-label study to fulfill this requirement is cost-effective and efficient, leveraging previous trial participants to expedite data collection.

The financial implications of the $124.2 million financing and the milestone-driven warrants are significant, providing the company with the capital necessary to continue its clinical development and potentially bring cytisinicline to market. The non-binding agreement with Silicon Valley Bank for the loan maturity extension offers additional financial flexibility. These financial arrangements suggest investor confidence in Achieve's pipeline and the potential market for smoking and vaping cessation treatments.

Healthcare Regulatory Expert

The FDA's guidance on the need for long-term safety data for cytisinicline reflects the agency's rigorous standards for chronic use medications. The agreement on a single open-label study is a testament to the constructive dialogue between Achieve and the FDA, which bodes well for future interactions during the NDA review process. The focus on safety beyond 12 weeks is crucial, considering the chronic nature of smoking addiction and the likelihood of relapse requiring repeated treatments. A robust safety profile will be essential for cytisinicline's market success and acceptance by healthcare providers.

From a regulatory perspective, the planned submission of safety data from subjects treated for up to one year is a proactive approach that may streamline the approval process. If the data supports the safety and efficacy of cytisinicline, it could lead to a label expansion for vaping cessation, addressing a growing public health concern. This expansion could significantly broaden the drug's target population and usage scenarios, enhancing its commercial potential.

Medical Research Analyst

The initiation of the ORCA-OL open-label exposure trial is a critical step in assessing the long-term safety of cytisinicline, which is necessary for chronic treatments like smoking cessation aids. The recruitment of over 1,700 subjects from previous trials demonstrates Achieve's ability to leverage existing data and participant pools to streamline research. This approach not only accelerates data collection but also ensures a more comprehensive safety profile by observing subjects who have varying durations of drug exposure.

The potential label expansion for vaping cessation mentioned by Achieve's President & Chief Medical Officer underscores the drug's versatility and could address a significant unmet need in nicotine dependence treatments. The long-term impact of such an expansion on public health could be substantial, given the rising prevalence of vaping, particularly among younger demographics. The success of the ORCA-OL study will be pivotal in determining the future clinical and commercial trajectory of cytisinicline.

Open-label exposure trial expected to initiate in Q2’24 with NDA filing anticipated in 1H 2025

SEATTLE and VANCOUVER, British Columbia, Feb. 29, 2024 (GLOBE NEWSWIRE) -- Achieve Life Sciences, Inc. (Nasdaq: ACHV), a late-stage pharmaceutical company committed to the global development and commercialization of cytisinicline for smoking cessation and nicotine dependence, today announced that it has reached agreement with the U.S. Food and Drug Administration (FDA) on the adequacy and timing of long-term cytisinicline exposure data requirements for a New Drug Application (NDA).

During pre-NDA discussions held in the fourth quarter of 2023, the FDA expressed support for an NDA submission based on adequate data to assess for efficacy from the two completed randomized and controlled Phase 3 trials, ORCA-2 and ORCA-3. In addition, the FDA advised that long-term exposure data to assess for safety beyond 12 weeks would be needed to adequately evaluate safety risks given that the FDA views smoking cessation drugs as products for chronic, repeat, or intermittent use as patients may relapse and require subsequent courses of treatment over a lifetime.

Achieve and the FDA have reached agreement that a single, open-label study evaluating for long-term safety exposure of cytisinicline will be sufficient to complete the requirement and enable an NDA submission anticipated in the first half of 2025. Based on FDA agreement, Achieve's NDA submission will include safety data on at least 300 subjects who have received cumulative cytisinicline treatment for six months. Prior to potential approval, Achieve will provide the FDA with safety data from at least 100 subjects treated with cytisinicline for a cumulative duration of one year.

Achieve plans to initiate the “ORCA-OL” open label exposure trial in the second quarter of 2024, which will include investigators and sites who have participated in the ORCA clinical trial program (ORCA-2, ORCA-3, and ORCA-V1 studies). ORCA-OL will recruit from the more than 1,700 subjects who have participated in these prior trials, including more than 1,100 who have already received cytisinicline treatment for either 6 or 12-weeks. The required total cumulative exposure data for NDA submission and potential final approval will combine the previous subjects’ treatment received during their respective ORCA-2, ORCA-3, or ORCA-V1 study participation plus their exposure during the ORCA-OL study. This allows for faster collection of cumulative long-term exposure safety data for the NDA submission. Subjects in ORCA-OL will receive cytisinicline treatment for up to one year and will be monitored for safety.

“We anticipate that data from this long-term exposure study will support the expected use of cytisinicline by patients multiple times throughout their journey to nicotine abstinence,” commented Cindy Jacobs, Achieve’s President & Chief Medical Officer. “Additionally, we expect this safety data will be supportive of a future cytisinicline label expansion for vaping cessation.”

Achieve also announced an approximately $124.2 million financing, which includes $60 million upfront from the sale of common stock and up to an additional $64.2 million upon the exercise of milestone-driven warrants. The milestone-driven warrants will expire on the earlier of (i) three and one-half years following the date of issuance and (ii) 30 days following Achieve’s public disclosure of the acceptance of an NDA for cytisinicline by the FDA in a Day 74 Letter or equivalent correspondence. Achieve has also reached non-binding agreement with Silicon Valley Bank on an extension of the maturity date into December 2025 on its outstanding loan.

“We are pleased to now have clarity from the FDA and we are excited about the vote of confidence from leading life science investors who share our enthusiasm for cytisinicline’s potential,” said John Bencich, Achieve’s Chief Executive Officer. “As we continue our discussions with potential commercial partners, we are funded to conduct the ORCA-OL trial and complete the planned NDA submission, bringing us closer to our goal of helping the millions of people who struggle with nicotine dependence.”

Achieve expects that existing cash, cash equivalents and restricted cash, together with the net proceeds from the financing, will provide adequate funding through the anticipated NDA filing in the first half of 2025. If all of the milestone-driven warrants are exercised in full, Achieve expects to have runway into 2026 and through potential FDA approval.

About Achieve and Cytisinicline 
Achieve’s focus is to address the global smoking health and nicotine addiction epidemic through the development and commercialization of cytisinicline. There are an estimated 28 million adults in the United States alone 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 87% of lung cancer deaths, 61% of all pulmonary disease deaths, and 32% of all deaths from coronary heart disease are attributable to smoking and exposure to secondhand smoke.³

In addition, there are over 11 million adults in the United States who use e-cigarettes, also known as vaping.³  In 2023, approximately 2.1 million middle and high school students in the United States reported using e-cigarettes.⁴ Currently, there are no FDA-approved treatments indicated specifically as an aid to nicotine e-cigarette cessation. 

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 withdrawal 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. For more information on cytisinicline and Achieve visit www.achievelifesciences.com.

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, statements regarding the completion of the offering, the expected net proceeds of the offering, the intended use of the proceeds of the offering and the expected sufficiency of such proceeds to fund the development of cytisinicline through potential FDA approval, data results and commercialization activities, the potential market size for cytisinicline, the potential benefits, efficacy, safety and tolerability of cytisinicline, the ability to discover and develop new uses for cytisinicline, including but not limited to as an e-cigarette cessation product, and the development and effectiveness of new treatments. 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 of cytisinicline; the risk that cytisinicline will not receive regulatory approval or be successfully commercialized; the risk that new developments in the smoking cessation landscape 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 conditions, including inflation, rising interest rates, instability in the global banking sector, and public health crises, such as the COVID-19 pandemic 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.

Investor Relations Contact
Nicole Jones
achv@cg.capital
(404) 736-3838

Media Contact
Glenn Silver
Glenn.Silver@Finnpartners.com
(646) 871-8485

References
¹Cornelius ME, Loretan CG, Jamal A, et al. Tobacco Product Use Among Adults – United States, 2021. MMWR Morb Mortal Wkly Rep 2023;72:475–483.
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.
⁴Birdsey J, Cornelius M, Jamal A, et al. Tobacco Product Use Among U.S. Middle and High School Students — National Youth Tobacco Survey, 2023. MMWR Morb Mortal Wkly Rep 2023;72:1173–1182. 

FAQ

When is the open-label exposure trial expected to initiate for Achieve Life Sciences, Inc.?

The open-label exposure trial is expected to initiate in the second quarter of 2024.

What is the anticipated timing for the NDA filing for cytisinicline by Achieve Life Sciences, Inc.?

Achieve Life Sciences, Inc. anticipates filing the NDA in the first half of 2025.

What is the total cumulative exposure data requirement for the NDA submission by Achieve Life Sciences, Inc.?

Achieve Life Sciences, Inc. plans to include safety data on at least 300 subjects treated with cytisinicline for six months and at least 100 subjects treated for a cumulative duration of one year.

How much financing did Achieve Life Sciences, Inc. secure, and what does it include?

Achieve Life Sciences, Inc. secured approximately $124.2 million financing, including $60 million upfront from the sale of common stock and up to an additional $64.2 million upon the exercise of milestone-driven warrants.

What is the maturity date extension agreement achieved by Achieve Life Sciences, Inc.?

Achieve Life Sciences, Inc. reached a non-binding agreement with Silicon Valley Bank to extend the maturity date into December 2025 on its outstanding loan.