Achieve Life Sciences, Inc. (NASDAQ:ACHV) has been busy since its previous quarterly update, adding new board members and executives and completing the long-term portion of its ORCA OL study which will generate critical safety data to be used in the new drug application (NDA) for smoking cessation. The R&D team held the end of Phase II (EoP2) meeting with the FDA to finalize the study design for the pivotal vaping trial. Management has shared its recent accomplishments at investor events including the Jefferies London Healthcare conference in November and the Piper Sandler Healthcare conference in December in New York. Management also participated in one-on-one meetings during the JP Morgan Healthcare Conference in San Francisco in January.
ORCA-OL Safety Trial
Achieve began 2025 with good news announcing that 300 participants had completed six months of treatment in the Ongoing Research of Cytisinicline for Addiction Program, Open Label (ORCA-OL) trial. The Data Safety Monitoring Committee (DSMC) identified no safety concerns as of this milestone allowing registrational filing with the FDA. Reaching this juncture places Achieve on track to submit its new drug application (NDA) to the FDA in 2Q:25.
ORCA-OL Background
After a launch in May 2024, the ORCA-OL trial began with rapid enrollment, high screening success rates and a single digit dropout rate. More than 650 subjects were enrolled with about two thirds already completing six or twelve weeks of treatment in previous ORCA trials when they started ORCA-OL. 29 sites actively enrolled for the trial with the objective of obtaining six months of safety data from 300 of these individuals in support of the anticipated filing of the NDA in 1H:25. On October 10th, Achieve completed enrollment with 479 participants. The company also passed its first Data Safety Monitoring Committee (DSMC) review for the trial, which concluded that there were no safety concerns.
The ORCA OL trial arose from the FDA’s desire for additional long-term cytisinicline exposure data to adequately assess safety risk. Despite an initial anticipated treatment duration of six to twelve weeks, cytisinicline could be used for chronic, repeat or intermittent use if a patient relapses. With this possibility guiding its interactions with drug sponsors, the FDA and Achieve reached an agreement that a single, open-label study evaluating long-term safety exposure of cytisinicline will meet the safety requirement. Details of the arrangement were provided in a February 29th press release and are described further below.
The completed study will include safety data on at least 300 subjects that have received cumulative cytisinicline treatment for six months. After the 300 subjects complete six months of treatment, Achieve expects a three-month turnaround to collect the data, analyze it and incorporate the safety data into the safety summary document for the new drug application (NDA). This suggests an NDA submission in the May timeframe. Generally, it takes about one year from NDA submission to receive a response from the FDA. While the FDA is reviewing the package, Achieve will submit the final 100 patients with one year of data (we estimate) somewhere around November 2025.
Vaping Indication
Last year, Achieve requested a Type B end of Phase II (EoP2) meeting with the FDA where the two parties began discussions for designing a pivotal trial in the vaping indication. The meeting has been held and Achieve obtained FDA agreement on the proposed single Phase III study design for cytisinicline treatment in vaping cessation. The agreement further outlined the additional requirements for submitting a supplemental new drug application (sNDA) to expand cytisinicline for the treatment for vaping cessation.
The EoP2 meeting solidified the proposed Phase III study design, including the inclusion/exclusion criteria, primary and secondary efficacy objectives, definition of vaping abstinence with biochemical verification, and other overall study assessments. The FDA agreed that one well-controlled Phase III trial (ORCA-V2), in addition to Achieve’s completed Phase 2 ORCA-V1 trial, would be acceptable for a vaping cessation indication as an sNDA. Additionally, the FDA agreed that the company’s safety exposure data from the ongoing ORCA-OL study would be adequate for the vaping cessation label expansion.
Vaping Trial Design:
Study population will be adults dependent on nicotine e-cigarettes and who have failed previous attempts to stop;
3 mg of cytisinicline will be dose 3x per day for 12 weeks vs. placebo in 800 vapers but not smokers with each group receiving behavioral support;
The primary endpoint is abstinence for the last four weeks of treatment and the secondary endpoint is continuous vaping cessation for weeks 9 to 24;
Safety, adherence to study treatment, and other patient-reported outcomes on vaping urges and craving symptoms will also be measured.
Last July, Achieve announced that the FDA had granted Breakthrough Therapy status for cytisinicline for the treatment of e-cigarette or vaping nicotine dependence. The designation is designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that they may demonstrate substantial improvement over available therapy on a clinically significant endpoint. The status provides for expedited development where Achieve can receive intensive guidance on drug development, have close contact with the senior managers and review staff at the agency, participate in rolling review and potentially be eligible for priority review, which can shave some time off of the approval process.
Management expects to leverage this expedited status to obtain a label that allows for adolescent use as this demographic uses vaping products at a much higher rate than older individuals. Additionally, in the December press release, it reiterated its 3Q:25 target for starting the single required Phase III vaping trial.
New Faces at Achieve
In early December, Achieve appointed Mark Oki as Chief Financial Officer who will take the financial reins of the company as it moves towards regulatory submission and commercialization of cytisinicline. He will be responsible for the company's financial strategy and operations, including accounting, investor relations, information technology, legal and other key administrative functions. Mark has a long history as CFO, serving in this role at Aytu BioPharma, Vivus and Alexza Pharmaceuticals during his executive career. Starting at Deloitte & Touche, Mark Oki offers over 25 years of professional experience. He is an alumnus of San Jose State University with a business administration degree in accounting.
Achieve also adds to its board, appointing two experienced healthcare executives who replaced a previous director, Dr. Vaughn Himes. Dr. Himes, who had previously served at Seagen, retired. The January 10th announcement introduced Kristen B. Slaoui, Ph.D. and Nancy R. Phelan to investors and stakeholders.
Dr. Kristen Slaoui, has served as the Chief Corporate Development Officer at Galderma, a leading global dermatology company, since 2020, and serves on the board of directors of Kinaset Therapeutics and the board of advisors of Advancing Innovation in Dermatology. She has led the effort to complete a number of significant transactions, including the 2021 acquisition of Alastin Skincare. Prior to joining Galderma, Dr. Slaoui spent 20 years at GSK, contributing to groundbreaking pulmonary disease research and the development of several approved medicines and held various roles of increasing seniority in Business Development teams, executing over $30 billion in deals, including major acquisitions like Stiefel Laboratories and Tesaro. She holds a B.S. in biology and classical studies from Gettysburg College, a Ph.D. in physiology from The Johns Hopkins University Bloomberg School of Public Health and completed a post-doctoral fellowship in pharmacology at the University of Washington School of Medicine.
Nancy R. Phelan, brings over 25 years of executive leadership in the biopharma and service industries. Nancy serves as Senior Vice President at Trinity Life Sciences and on the boards of directors of Medexus Pharmaceuticals and FemmePharma. At Trinity Life Sciences, Nancy has launched and heads a new Center of Excellence dedicated to data and analytics driven digital transformation and innovative customer engagement solutions with a focus on cutting-edge technology and AI. Nancy’s extensive pharmaceutical business model transformation and customer engagement commercialization expertise spans prescription and over-the-counter drugs. Prior to Trinity Life Sciences, Nancy was a Senior Vice President, Omnichannel Activation at Indegene and also held leadership roles at global pharmaceutical companies Novartis, Bristol Myers Squibb and Pfizer. Throughout her career, Nancy has led commercialization strategies and launches which have generated significant revenue growth and market expansion. She has received many industry awards including MM+M Woman of Distinction, DTC Hall of Fame, PM 360 ELITE Digital Crusader, Working Mother Cover Mom and Pharmaceutical Executive 40 under 40. Ms. Phelan holds a B.A. with Honors in history from Franklin & Marshall College.
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