What's Next In Smoking Cessation Therapies: A Q&A With Qnovia CEO Brian Quigley And Advisor Mitch Zeller
A Q&A with Qnovia CEO Brian Quigley and Qnovia Advisor Mitch Zeller
While anecdotal evidence might suggest far fewer people are smoking cigarettes, the fact remains that many people still smoke. And what’s more, they struggle with quitting. More than two-thirds of smokers intend to quit, but less than one in 10 is successful.
One suggested jumpstart to a new wave of smoking cessation therapies is more encouragement from the FDA. In April, a panel of public health experts published an article in The New England Journal of Medicine imploring FDA to do more. And in what felt like an immediate answer to the call was a statement by FDA Commissioner Dr. Robert Califf affirming as much and the issuance of a final guidance on nicotine replacement therapies (NRTs).
For its part, Qnovia is already on the path to commercializing the first-ever inhaled prescription smoking cessation therapy, RespirRX. To discuss the immediate public health need and the future of NRTs, we held a Q&A with Qnovia CEO Brian Quigley and Qnovia advisor and former director of the FDA’s Center for Tobacco Products Mitch Zeller.
Nicotine replacement therapies include over-the-counter skin patches, chewing gum, and lozenges; prescription nicotine sprays and inhalers; and prescription tablets that do not contain nicotine. But you contend that these options, some of them long-standing, aren’t all that successful. What is the likelihood someone will quit smoking with any one of these, and why isn’t that an acceptable outcome?
ZELLER: There are multiple reasons why existing NRT products do not do all that well in the real world and ultimately lead to cessation rates much lower than in the experimental clinical trial setting. Those who quit without assistance of NRTs have exceptionally low success rates of 3-7% and present a high level of relapse. Those who quit using currently available NRTs don’t fare much better, because outside of tightly controlled clinical trials, long-term cessation rates are only marginally higher than those reported with placebos — in the 3-8% range.1,2,3
One key limitation of these products as used by consumers is the nicotine delivery. Oral and dermal delivery of nicotine can take over 30 minutes. By contrast, a cigarette delivers nicotine to the brain in less than 10 seconds. Another reason for the relative lack of success of existing NRTs in the real world relates to inadequate patient compliance, either not taking the products long enough or not taking enough of the product.
In a recent interview with CNBC, FDA Commissioner Dr. Robert Califf also noted the need for new tobacco cessation products — which “the industry is not really producing.” Why do think that is?
ZELLER: Part of the explanation is the chicken and egg dynamic in play here. Industry is not looking for any sort of guarantee of marketing authorization from the FDA. But drug delivery via inhalation raises some unique safety issues and industry needs to know that FDA is open to considering applications for products employing this innovative technology. So far, there has not been much signal-sending from the agency.
Califf also advocated for incentives to help drive NRT development, much like those used to advance cures for cancer and rare diseases. What could an incentive program for NRTs look like, and what would be the anticipated outcome?
ZELLER: For any incentive, whether financial or process related, the goal needs to be designed to have more commercial entities pursue drug approval for cessation therapies that work. Generally, the process is viewed as expensive and complex, and since smoking is an age-old problem, many companies are directing R&D resources into new therapeutic areas. Incentives could take the form of guidance to clarify key scientific questions from sponsors or creating unique accelerated pathways that are indication specific. Many things can be done without sacrificing the FDA’s safety and efficacy standards while accelerating the access to new therapies.
Aside from incentives, why is finding more successful treatments for smoking cessation so crucial to public health?
ZELLER: Tobacco use remains the leading cause of preventable disease and death in the United States. This remains the state of play despite the historically low cigarette smoking rates we currently see for adults and youth. There is really a desperate need for new and innovative treatments for tobacco cessation. Oral and dermal NRT products simply do not deliver enough nicotine fast enough to help large numbers of smokers successfully quit. With FDA getting closer to banning menthol in cigarettes and advancing a policy to limit nicotine levels in cigarettes, there will likely be millions of smokers with a newfound interest in quitting. What tools will they and their doctors have to give them the best chance of succeeding?
As we’ve mentioned, NRTs come in various dosage forms — but there are currently no prescribed inhalants. However, you serve on the advisory board at Qnovia, a pharma company developing an inhalation device for smoking cessation called RespiRx. What is advantageous about the inhalant approach, as opposed to the others?
ZELLER: Qnovia is using a mesh nebulizer to deliver inhaled nicotine to the lungs. This could be a breakthrough as it will come much closer to duplicating the pharmacokinetic profile for nicotine delivery from a combustible cigarette. But, of course, there is no tobacco in the Qnovia product, and their technology does not even require the nicotine to be heated. So, there is going to be a very strong safety profile coupled with rapid delivery of medicinal nicotine. This could be a treatment specialist’s dream.
Though the field for NRTs might be stark now, what do you see for this part of the industry in the coming years?
ZELLER: I am excited from a public health perspective at the potential for an inhaled medicinal nicotine therapy to be a true breakthrough in tobacco cessation. We have been fighting a 21st century public health problem with extremely limited 20th century tools. Companies like Qnovia, that are ready, willing, and able to engage with drug regulators, answer their questions, and do the science, are poised to help us address what sadly remains the leading cause of completely preventable disease and death worldwide.
At what stage is Qnovia’s RespiRx in the FDA approval process, and when do you anticipate in-human clinical trials?
QUIGLEY: Qnovia completed its pre-IND and has executed all the safety studies outlined with FDA. The company is currently advancing to an IND submission later this year and will begin human clinical trials in the U.S. immediately following the IND opening from FDA.
According to a 2020 Surgeon General’s report, 68% of adult smokers said they wanted to quit smoking. Yet, of those who tried, only 7.5% succeeded. Understanding the desire exists, what is your expectation of patient recruitment and enrollment when it comes time for Phase 1 trials?
QUIGLEY: Qnovia has clear agreement with FDA on the population and powering of its clinical plan from Phase 1 through Phase 3. The Phase 1 PK study is a relatively small study, and recruitment and enrollment will be fairly straightforward.
And knowing the FDA’s commitment to diverse patient populations in clinical research, what measures will Qnovia take to ensure it’s meeting FDA requirements and reaching its target patient population?
QUIGLEY: The larger Phase 2 and 3 studies will be enrolling patients in the hundreds. It is of particular importance that study subjects reflect the population of patients across all socioeconomic metrics. Qnovia uses leading CROs to conduct our studies and is confident it can achieve this goal.
References:
- Rigotti, Nancy A. (Oct 17, 2012). “Strategies to help a smoker who is struggling to quit”. JAMA. 308 (15): 1573–1580
- Kotz, D., Brown, J., and West, R. ‘Real-world’ effectiveness of smoking cessation treatments: a population study. Addiction. 2014; 109: 491–499
- Quitlines and nicotine replacement for smoking cessation: do we need to change policy? Pierce JP, Cummins SE, White a.MM, Humphrey A, Messer K. Annu Rev Public Health. 2012 Apr;33:341-56. doi:10.1146/annurev-publhealth-031811-b.124624. Epub 2012 Jan 3. Review.
About The Experts:
Brian Quigley is the CEO of Qnovia, Inc., a California venture-backed health technology company focused on commercializing proprietary inhalation device technologies to improve patient outcomes. Qnovia’s Respira is currently engaged with FDA CEDR to pursue a combination product authorization as the first inhalable prescription smoking cessation therapy.
Brian has 25 years of marketing, regulatory, operations, and general management experience for public companies, private equity-backed businesses, and venture-backed businesses. He developed a focus on inhalation devices through his time in tobacco, which gave him an understanding of the risks of tobacco use, the opportunity to reduce risks for smokers, and the current generation of technologies.
Prior to Qnovia, Brian spent 16 years at Altria Group, with seven years as president & CEO for Altria’s Smokeless and Innovative Products/Vapor Businesses. Brian has also been an active venture investor in both the cannabis and alcohol spaces, and he sits on the boards of Mustgrow Biologics and Belle Isle Craft Spirits. He lives in Richmond, VA, with his wife Amy and three sons.
Mitch Zeller, J.D. — now a Qnovia advisor — retired in April 2022 as the director of the FDA's Center for Tobacco Products. Zeller led FDA's efforts to use the tools of product regulation to reduce disease and death from tobacco use and bring previously unavailable information about its dangers to light.
In 1993, Zeller joined the staff of then-FDA Commissioner Dr. David Kessler, M.D. What began as a two-week assignment by Kessler in 1994 to examine the practices of the tobacco industry led to his serving as associate commissioner and director of FDA's first Office of Tobacco Programs. Zeller also served as an official U.S. delegate to the World Health Organization (WHO) Working Group for the Framework Convention on Tobacco Control.
In 2000, Zeller left the FDA to continue his work for tobacco control as executive vice president of the American Legacy Foundation. In 2002, Zeller joined Pinney Associates where, as senior vice president, he provided strategic planning and communications advice on domestic and global public health policy issues involving the treatment of tobacco dependence and the regulation of tobacco products and pharmaceuticals. He left Pinney Associates in 2013 upon his return to the FDA as center director.