Q&A: Addressing lack of safe, effective smoking cessation therapies
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Key takeaways:
- For cigarette smokers who want to quit, nicotine replacement therapies have remained the same over recent years.
- Innovation is needed in this space to help those who have tried everything to quit.
Although a recent report from the CDC showed that cigarette smoking in 2021 is the lowest it has been since 1965, millions of people continue to smoke, with many struggling to quit with the current authorized treatments.
Individuals who want to quit smoking cigarettes may choose a reduced-risk product (e-cigarettes) or pharmacotherapy; however, more research is needed to understand how reduced-risk products may increase risk for cardiovascular and pulmonary events.
Further, there has been a lack of new nicotine replacement therapies developed and authorized.
To learn more about smoking cessation treatments, challenges smokers face when trying to quit and the role government has played in this space, Healio spoke with Brian Quigley, BA, CEO of Qnovia, and Jasjit S. Ahluwalia, MD, MPH, MS, chairman of the scientific advisory committee at Qnovia, as well as professor of behavioral and social sciences and internal medicine at Brown University’s School of Public Health and The Warren Alpert Medical School.
Healio: Could you explain the difference between reduced-risk products and pharmacotherapies for use in people who want to quit smoking?
Quigley: In the world of people trying to solve the problem of death and disease caused by combustible products, there are reduced-risk products — e-cigarettes — as well as pharmacotherapies that can be prescribed to help people quit. Both of these product categories play very different, but also complementary, roles in that fight to reduce smoking.
The usage of e-cigarettes is driven by smokers who know the harm of the product they are using and are looking for alternatives. In some cases, people are not quite ready to fully commit to quitting, so they are looking for alternatives.
In the U.S., approximately 20 million smokers each year will attempt to quit, and when you ask them how they plan to quit, the No. 1 way in 2023 is cold turkey because the existing pharmacotherapies (gums and patches) really aren’t effective in the real world.
Healio: According to data from the CDC , e-cigarette use rose from 2020 to 2021. What recent efforts have governments made to limit the use of e-cigarette devices?
Ahluwalia: Oddly enough, the No. 2 way people quit after cold turkey in the U.S. is no longer FDA-approved medications — it is e-cigarettes. This is true in the U.K. and a number of countries around the world, especially where they are not banned. About 30 countries have banned them outright, which I think was a bad idea. We know about the prohibition of alcohol; everything goes underground and leads to bad things happening, such as tainted and unregulated products. The federal government has generally failed at e-cigarette regulation, and the CDC came at it way too late.
Quigley: We are currently working on submitting comments to the U.S. Department of Health and Human Services — the leader of the agencies in the U.S. that are shaping policy — because they have a request for information on this framework for accelerating smoking cessation. In that plan, there was nothing about developing new pharmacotherapies to help smokers quit, and that’s a problem. Compare that with the U.K. and the Medicines and Healthcare products Regulatory Agency (MHRA), who have taken a much more progressive approach, have been very thoughtful and created new frameworks and regulatory pathways for not only products like ours, but even e-cigarettes to be designated as a medicine to help people quit. The MHRA is currently a shining example of a progressive, more balanced view even though they are now dealing with their own issues of disposable products.
Looking at what’s going on in the U.S., we think it’s critically important that these new therapies are developed. We think the FDA has an opportunity and responsibility to play a bigger role with industry.
Ahluwalia: The last smoking cessation therapy approved by the FDA on the CDER side was 22 years ago with Chantix (varenicline tartrate, Pfizer), hence the need for a new and safe product to fill in this void space.
Healio: What are some challenges cigarette users and e-cigarette users face when trying to quit?
Quigley: Individuals quitting cigarettes and e-cigarettes have a lot of the same issues. For cigarette users specifically, challenges include physiological addiction and behavioral components, such as hand-to-mouth motion, which are all wrapped around the experience. We’re trying to solve for a bundle that can be proven safe, effective and addresses, one, the physiological dependence to nicotine more effectively and, two, a form factor because we’re delivering that via inhalation.
In delivering drugs to the body, inhalation is a very effective way to get nicotine into the bloodstream. It’s why when someone smokes a cigarette, within seconds the nicotine spikes and the pharmacokinetic profile is a very steep, high curve. Because the existing pharmacotherapies — gums and patches — deliver the nicotine transdermally or transmucosally, they result in a very low level of nicotine.
We need to close the 20-plus-year gap of a lack of innovation in approved drugs that can be prescribed to help these individuals get there. Even though people talk all the time about how prevalence of combustible tobacco use is at an all-time low, the absolute number of smokers in the U.S. has been relatively flat for 15 years because the population keeps growing. People like to think that we’re winning the battle, but we’re making no progress at all. We need more innovations and therapies to help those who want to quit.
Ahluwalia: Every smoker is different. That’s why there’s no one panacea. We should have a nonjudgmental approach. Individuals who are smoking often are people who face challenges and issues in their lives. Behind everything, there’s a real human being. Physicians do not forget that, but policymakers and naysayers I feel sometimes do.
Healio: What product are you working on to overcome those challenges?
Quigley: At Qnovia we’re trying to learn a bit from what e-cigarettes have demonstrated, which is delivering nicotine via inhalation, but we’re using a technology that can achieve the standard of safety set by the Center for Drug Evaluation and Research (CDER); it utilizes a proprietary aerosol platform without the use of heat to deliver an aerosol in a particle size to get the nicotine deep in the lung, but it delivers the nicotine fast enough and at a high enough level to alleviate the withdrawal symptoms. To be approved by CDER, there is a very high bar and standard for safety and very strict standards for how the device performs repeatedly because you’re delivering a drug that has to be delivered precisely every single dose and function in a whole host of different environments.
We’re able to deliver that nicotine and a pharmacokinetic profile that is not as high as a cigarette but much closer to help that person get through their cravings. Additionally, the device itself is a smart device, so over the 12 weeks, it titrates their available nicotine doses, controls how much they can use it a day and forces them to get more confident in overcoming all of those barriers while still delivering some of the hand-to-mouth behavioral aspects so they can ultimately quit.
A major component in quitting is the mindset. One smoker can view switching to any e-cigarette completely as quitting smoking, and that may be sufficient, but it’s a very different mindset of a patient who says, ‘I no longer want to be addicted, use nicotine or smoke.’
Healio: What treatments are currently authorized for individuals who want to quit smoking cigarettes and/or e-cigarettes? Are there any additional products designed to help individuals quit pending authorization from the FDA or currently being tested?
Ahluwalia: For smokers, nicotine replacement therapies include nicotine gum, nicotine patches, nicotine lozenges and a nicotine inhaler. There are also prescription drugs that do not contain nicotine, such as bupropion (Zyban, GlaxoSmithKline), which was first found to be an antidepressant then discovered to work for smoking, and varenicline tartrate, an agonist and antagonist to the nicotine receptor.
On the e-cigarette side, there are around 20 products that have been authorized to be sold in the U.S. There are no menthol e-cigarettes that are authorized, but “nonflavored” tobacco/original/generic flavor is authorized.
Quigley: In terms of what’s coming, Achieve Life Sciences has announced phase 3 data for cytisinicline, but I think the short answer of what’s coming next is not enough. There needs to be more innovations because not one solution is going to work for everybody. We are about to submit our investigational new drug (IND) application, which will allow us to begin our human clinical study. There are also a few other companies behind us that have just completed their pre-IND.
Ahluwalia: Interestingly, there is a possible chance that semaglutide (Ozempic, Novo Nordisk) may benefit smokers because it works on the reward pathway. There is scientific interest and I suspect soon there will be clinical trials and further research in this space. Additionally, at The Johns Hopkins Center for Psychedelic & Consciousness Research, psilocybin has been shown to have short-term efficacy for smoking cessation, and an ongoing NIH-funded clinical trial is underway. The prevalence has gone down but you still have 40 million Americans using cigarettes in any given month. We need to keep pursuing every angle possible.
Quigley: Depending on the study you look at in the real world, the nicotine replacement therapy products are in the mid-single digits for efficacy, and relapse does occur. In essence, there are not enough new drugs in the pipeline. The good news is I think more and more people are going to be focused on it because it’s a massive public health opportunity and a massive financial opportunity. At the end of the day, we need therapies that can not only get approved but can also be used and effective at scale to really move the needle.
Ahluwalia: Nicotine delivery products, patches, gum, etc, are some of the cleanest drugs, so Qnovia’s job is to show that its product is not only efficacious but also safe. If that’s done, then it’s a clean drug, it’s just nicotine, so side effects should be low. Further, efficacy could be one of the highest in the CDER-approved drugs because the delivery platform, which is the pulmonary respiratory system. This is a very efficient way to get nicotine to reach the alveoli, then on to the central nervous system and ultimately bind to the nicotinic receptor before it gets metabolized by the liver.
Healio: Have there been any technological advancements in helping smokers quit?
Quigley: The lack of new therapy, drugs or pharmacotherapies to really help smokers has been filled by a lot of folks working on behavioral change management tools, online portals, and apps. People have also tried to create a system to reinforce the positive benefits of not smoking by looking at carbon monoxide levels because it is one of the very early biomarkers in breath to show that something is happening when we stop smoking.
In our initial application, we’re not including a behavioral app interface, but the device is Bluetooth enabled. Once we get approved, we'll come back with a supplemental to include that aspect because I think there are elements of data and information to the actual user to help support them in their journey. For now, the device has a screen and a user interface that shows users what day they are on the therapy, how many doses they have available and will give reinforcement messages.
Healio: Who should take charge in helping combat the harmful effects of smoking?
Quigley: Everybody knows smoking continues to be the leading cause of preventable death and disease in this country, but it seems like people have just kind of taken that as fact and that it can’t change. There is a shared responsibility to industry, not only to us, but to other companies to invest in this space. There is also responsibility to the FDA because we cannot be satisfied with the status quo that exists today.
We’re committed to helping the millions of people who feel left behind after trying to quit dozens of times. We need to have a product that doctors will prescribe and that will be broadly available to people of every different socioeconomic status. If we had a ticker counting how many people died from smoking like we did during the COVID-19 pandemic, I think a lot more people would be focused on it.
Ahluwalia: It’s really important that physicians be pragmatic and worry about the smoker and what’s best for the person who is addicted. If smokers can’t quit until new products are on the market, the surrogate goal can be reducing harm — not getting off all nicotine completely, but getting off combustible cigarettes.
Reference:
- Prescription NRT. Qnovia. https://www.qnovia.com/nrt/. Accessed July 21, 2023.