Hi, I’m Ian Fearon I’m the Director of WhatIF? Consulting Limited and Chief Scientific Officer with McKinney Regulatory Science Advisors. What I’m going talk about in this presentation are medicinal electronic cigarettes, or e-cigarettes, and how I believe that providing an electronic cigarette on prescription to help smokers stop smoking is a great unmet public health need, which can really help in the battle against the death and disease caused by combustible cigarette smoking.
There are four main themes of this presentation
- I’m going to talk about the unmet need and how big is that unmet need.
- I’m going to talk about what is contributing to the problem, what’s adding to it.
- I will then speak about if, from a manufacturers perspective, if you want to help meet the unmet medical need for electronic cigarettes, how might you go about doing it.
- Finally, I’ll briefly touch on who will benefit from a medicinal e-cigarette and how will they benefit.
Before I go through the presentation, first some disclosures: Through whatIF? Consulting and McKinney Regulatory Science Advisors, I provide scientific and regulatory advice and support to e-cigarette manufacturers and also to drug companies. I’m also a Scientific Advisory Board member with QNovia, a drug company who developed an inhaled nicotine therapeutic, for which they’re attempting to obtain a medicinal license as a nicotine replacement therapy. Anything I do say in this presentation all my own views and considerations.
What is the unmet need and how big is that unmet need?
In the United states, over 28 million people still smoke combustible cigarettes. In the United Kingdom, 6.4 million people still smoke cigarettes. Around the world, 1.1 billion people all current cigarette smokers, and of course, each one of these cigarette smokers is placing themselves at increased risk of heart disease, lung disease, and cancer due to cigarette smoking habit.
The New Approaches conference, which this presentation was made, in September of this year lasted for about 11 hours and in those 11 hours, an astonishing 602 American citizens who were cigarette smokers will have died due to their cigarette smoking habit. Around the world, it is predicted that in this century, unless the status quo is changed and we do something to help smokers stop smoking, then a billion smokers will lose their lives around the world.
E-cigarettes vs current prescription medicine
So what is contributing to the problem? What this graph shows, is if you gave 100 smokers each of the products listed along the bottom, to help them stop smoking and ask them to use it and to stop smoking, how many of them will actually succeed? If you took the 100 smokers and ask them to quit, but didn’t get them any support, approximately three of them will be able to stop smoking. While nicotine gum is twice as effective as quitting cold turkey, it’s still not very good and helps approximately 7% of smokers to stop smoking. Even the best therapeutic aid to stopping smoking dramatically only helps approximately one in five smokers to stop smoking.
It’s important that you place these data in the context of other drugs which are available to treat human disease. Now on the right hand side are the top three prescription drugs in the United States and if we take the middle one amoxicillin, which is an antibiotic used to treat lung infections in cigarette smokers, if you gave 100 cigarette smokers with a lung infection amoxicillin, over 90% of them would have that infection cleared up.
So when you relate the efficacy of these prescription medicines to licensed medicinal products to help people quit smoking, the medicinal products, or the NRT products, just aren’t very good. What’s also surprising is that the middle bar that just appeared here, the 38% bar, this is the efficacy of Juul in helping people quit smoking. If you gave 100 smokers a Juul e-cigarette and ask them to stop smoking, data has shown that 38% of them six months later completely quit smoking. What this really demonstrates is that an e-cigarettes are good at helping people quit smoking, and they’re potentially way better than the current prescription medicines that are given to smokers each and every day around the world.
Misinformation around e-cigarettes
The other thing that’s contributing to the problem is misinformation. Recent data from the ASH survey in the United Kingdom showed that 40% of smokers wrongly believe that using electronic cigarette is equally or more harmful than cigarette smoking.
On the way to the New Approaches Conference, I was in Germany also attending a conference. I’m leaving the hotel early on Friday morning, there’s a 24 year old cigarette smoker from Norway I asked him as he was puffing around his cigarette whether he ever thought about using an electronic cigarette as a less harmful means of getting the nicotine that he craved? His response was “no e-cigarettes are way, way, way more harmful than cigarette smoking” and it’s an anecdote, but it’s another example of how people wrongly believe that e-cigarettes are harmful and this prevents switching to them and prevents them giving up smoking combustible cigarettes.
Why are there no prescription electronic cigarettes currently available to doctors to prescribe?
The reality is that some e-cigarettes, or e-cigarette like products, have received prescription licenses in the United Kingdom. The voke inhaler, which isn’t a classic electronic cigarette, it’s a gas-powered nicotine inhaler, and the e-voke ciga-lite electronic cigarette, received authorizations from the MHRA about 10 years ago, but neither of them made it to market and neither of them have ever been prescribed by a physician.
Companies have tried, or are trying, in the United States to get the electronic cigarette license or prescription medicine. Hail therapeutics have tried, but due to various problems they’ve now pivoted into the UK pathway instead, and QNovia with their Respirorics product are trying to get medicinal approval in the United States, as well as in the United Kingdom. As of right now, there are no electronic cigarettes currently prescribed by physicians to help smokers stop smoking, despite the fact that they will likely help smokers stop smoking.
If you are a manufacturer and you want to help meet the unmet medical need of a prescription e-cigarette, how might you go about it?
The reality is you can get a prescription license for an e-cigarette pretty much anywhere in the world, but the two countries with the best articulated pathways are the United Kingdom and the United States and so I’m just going to focus on these two countries.
Manufacturers in the United Kingdom
Starting with the United Kingdom, you have to fully characterize the emissions from your electronic cigarette, but your benchmark or your comparator is cigarette smoke. The MHRA is a very pragmatic regulator and understands that the emissions from your e-cigarettes should be compared to the thing that cigarette smokers are inhaling each and every day. Therefore, you benchmark against cigarette smoke.
In the UK, you have to do toxicology studies, you don’t need to do animal experiments. You can use a desk based risk assessment, a computer assessment approach and support the output from that desk based risk-assessment with in-vitro toxicological studies as appropriate. In terms of clinical trials, you only need to conduct one clinical trial in the United Kingdom and your efficacy measure is nicotine delivery. What the MHRA really want to see, is that your e-cigarette delivers nicotine to a greater degree than a comparator currently licensed product, such as the nicotine inhaler, but doesn’t deliver nicotine to a greater degree than combustible cigarettes.
Manufacturers in the United States
In the United States, you still have to fully characterize the emissions from your electronic cigarette, but your benchmark in the United States is not cigarette smoke, it’s fresh air, and this could be problematic. For example, if your e-cigarette heat say solution containing PG and BG, you might generate trace levels of aldehydes and of course those trace levels of aldehydes will be greater than levels of aldehydes in fresh air, and this means that you then have some explaining to do to FDA in order to justify the safety of your e-cigarette product before they will grant you a license.
In the US, you do have to do significant numbers of costly and time consuming animal experiments in numerous species of animals and for time periods of up to two years in time. And you have to assess reproductive toxicity, general toxicity, carcinogenicity, etc. in these animal studies and as I say these are expensive and these are time consuming.
The efficacy measure in the United states is also very, very different. You still have to do a nicotine delivery study looking at how much nicotine smokers get from your electronic cigarette, but your efficacy measure is not nicotine delivery, your efficacy measure is helping smokers quit. You have to run a smoking cessation trial and similar to the animal studies smoking cessation trials are expensive and they’re time consuming, and you might have for example to recruit 1000 smokers and follow them for up to a year to see whether your product is helping quit smoking or not.
What do you need to optimize if you’re designing medicinal e-cigarettes?
Well, you got to think about abuse liability. Nicotone delivery, for example, does your product deliver enough nicotine that smokers find satisfying? Does it reduce cravings and withdrawal symptoms? Does it deliver too much nicotine so that the regulator won’t authorize it? Does it create positive subjective effects, so do smokers find it satisfying, do they like using it, are they likely to use it in the future to help them to stop smoking, so you have to think about abuse liability.
You have to think about flavors, and these are a good thing in the prescription model. We know that adult smokers like flavors and they help them stop smoking, and of course you’re not going to create a youth use issue due to the restrictive access to prescription electronic cigarettes.
You need to think about other ingredients as each and every ingredient in your liquid has to be safe and you need to demonstrate that to the regulator. And what I tell the companies I consult for is that simplicity is key. The more compounds and chemicals ingredients you have in your e- cigarette liquid, the more data you can have to generate to demonstrate to the regulator that use of your e-cigarette is safe.
Finally, you’re going to have to think about delivered dose uniformity. What regulators need assuring is that your product delivers a uniform dose of nicotine regardless of where your product is in its lifetime. So, for example, if your e-cigarettes battery is completely full and your e-cigarette battery is half empty, does it still deliver the same amount of nicotine per dose and each time somebody puffs on it. Or when you’re e-liquid cartridge is full and when your e-liquid cartridge is half empty, does your product still deliver the same dose of nicotine?
So you really have to think about this, and I always encourage manufacturers to do this right at the very start of their design process, because if you do discover that you have a delivered dose uniformity issue after you’ve conducted your scientific experiments, your toxicology studies, or all your clinical study, you’ll have to redo those experiments which should tweak your device to meet the delivered dose uniformity guidelines.
What else might you have to think about? Well you have to think about terminology, and although these may just seem like words, they define how your product and your company will be treated by the regulator. The nicotine in your electronic cigarettes a drug and must meet drug purity standards. You e-cigarette a medical device and must meet medical device standards and it will be called a nicotine inhaler. You have to think carefully about uniform nicotine delivery, and I talked about this on the previous slide, but you really have to make sure early on in the design process that delivery of nicotine from your device is uniform and that your product meets delivered dose uniformity standards.
You have to think about the manufacturing processes and ensure you’re manufacturing meets the fairly stringent medical manufacturing standards that regulators require. You need to think about how you’re going to get doctors to prescribe your electronic cigarette once it’s been authorized and the medical science liaison people that you’re going to get to walk into doctor’s offices to convince them to prescribe your electronic cigarette.
You need to think about pharmacovigilance, post-market surveillance, and how you’re going to assess what your product is marketed and that it continues to be safe in the hands of the people that are using it, and to make sure that you have in place safety reporting system both for physicians and for the users of your product.
You’re going to have to think about what to call your product, particularly if your product is already a consumer product because you can’t have a consumer electronic cigarette and a prescription electronic cigarette with the same name. Similarly you’ll have to talk and think about cross compatibility, if you have for example a pod based electronic cigarette you’re cannot have a prescription pod which fits into a consumer device and vice versa, so these are just some of the things that you’ll have to think about during the lifetime of your medicinal licensing project.
You also have to think about the regulator and how you interact with them. In my experience regulators are armed and highly dangerous, but they do want to help you get to where you want to go, to help you cross the road. But you do have to listen to them and anything they do say you should follow their advice as strictly as you can ,and they will help you get to where you want to go.
Who will benefit from prescription e-cigarettes?
I talked earlier on about the misperceptions of vaping that exists at the moment and those misperceptions are growing. I think though that once an electronic cigarette receives a prescription license, that will fix some of the poor messaging that people are hearing about electronic cigarettes and will improve their beliefs among the general public and among smokers and vapers, are a much less harmful alternative to cigarette smoking, and can help them stop smoking. So there will be some kind of Halo effect on the whole e-cigarette category once a manufacturer, or several manufacturers, obtain prescription licenses for e-cigarettes.
The company itself will benefit. These data are from Bloomberg and they predicted that the nicotine replacement therapy market will grow to over $100 billion market globally in the next five years or so. That’s a huge market and don’t forget that market is one which provides products to smokers actually work, and if your product does work and it does deliver nicotine and it does help smokers stop smoking, doctors are going to prefer to describe your product to the nictoine patches and gums and pharmaceutical products that currently exist. You will gain a significant proportion of that $100 billion market.
Fnally, and most importantly in my mind, are the cigarette smokers and their families. Each and every day thousands of people across the world die due to combustible cigarettes smoking this impacts them and this impacts their families to reduce degree there are massive benefits to improving the lives of smokers and their families by providing them with better products to help them quit smoking.
Summary
- Prescription electronic cigarettes is a huge, and currently unmet public health need.
- There will be a significant financial benefit to manufacturers.
- The UK licensing pathway is significantly easier to navigate, although there may be lower cost/less time involved and UK licensing application, this is significantly offset by the smaller market size in the UK compared with the United States.
- There were many technical and scientific challenges to obtaining a prescription license for an e-cigarette. These challenges are difficult but they’re not insurmountable and for each and every aspect of your licensing process you need to seek expert advice including advice from the agencies, the regulators themselves including the FDA and the MHRA.
- Going fast will slow down. This is not an easy process, and it’s like running with a parachute the faster you run the harder it becomes, so you have to be methodical think about your application think about what you need to do and go slowly and you will get to the end of the licensing process.
Thank you for listening. If you have any questions or anything we’ve said in this presentation, please do reach out to me through WhatIF? Consulting or McKinney Regulatory Science Advisors. We’d love to answer any questions you have and support you moving forward if you’re interested in obtaining a prescription license for an electronic cigarette.
About Ian Fearon
Ian is a Clinical R&D expert and scientist who’s spent 16 years in tobacco harm reduction providing end-to-end support developing and implementing pre-clinical and clinical research programs for tobacco regulatory submissions in the EU and US. Ian is also a technical writer and subject matter expert in all tobacco harm reduction areas.