Updated: 17 February 2021

Dr. Andrea Costantini holds an MD, specializing in Clinical Pharmacology. Before working with PMI, Dr. Costantini spent more than 15 years in the pharmaceutical industry.  Her expertise includes respiratory medicine, mainly asthma and COPD, and clinical research.

 

Core Concepts line  
The totality of the available evidence today strongly indicates that switching to our heated tobacco system, although it is not risk free, is a much better alternative than continuing to smoke for those adult smokers who otherwise would keep smoking.

Dr. Andrea Costantini, Head of Regional Scientific Engagement Latin America & Canada

Below is the transcript of the video:

Hello, I’m Andrea Costantini, I’m a medical doctor specialized in clinical pharmacology and I work at PMI as Head of Scientific Engagement for the Latin America and Canada Region.

First of all, I would like to thank Mikael for taking us through the equation that explains how to improve public health and, as mentioned by him, my presentation will focus on the product risk reduction using the results of our tobacco heating system demonstrated by science.

When we look deeper at what science is needed to support reduced risk products, we have identified four important components:

1. Absence of combustion,

2. Reduced toxic emission,

3. Reduced exposure and

4. Reduced disease.

To begin, let’s look at absence of combustion.

Public health

Can scientifically substantiated smoke-free products positively contribute to public health?

Product acceptance and use

Product acceptance and use

Combustion only occurs when the three main elements are combined: fuel, heat, and oxygen. When even one element is removed, combustion cannot occur. Putting it in the context of cigarettes, and specifically cigarette combustion, the tobacco is the fuel. By combining it with oxygen and igniting the cigarette, it generates energy, smoke, and ash. Let’s look in detail at what happens at the lit end of the cigarette.

The tobacco ignites at temperatures above 400 °C, and it reaches temperatures above 800 °C during a puff, since oxygen is brought in to fuel the fire while inhaling.

When heating tobacco in the tobacco heating system, maximum temperature reached by the tobacco is below 350 °C. Its temperature decreases during every puff, contrary to what we have seen in cigarettes, since fresh, cool air is being drawn into it. Once the heating system is turned off, tobacco temperature immediately decreases as there is no heating source. Finally, we have evaluated the performance of our system in different atmospheres with and without oxygen.

We have found that the composition of the aerosol generated when it is operated in an atmosphere without oxygen is very similar to the one that is generated in the presence of it. All this is demonstrating that combustion does not occur in the tobacco heating system. Several internationally recognized experts in combustion have looked at the data and have confirmed the absence of combustion in our tobacco heating system.

Now let’s move to reduced toxic emissions. As tobacco temperature goes up, the generation of harmful and potentially harmful constituents, or HPHCs as we call them for short, increases. And they significantly go up once combustion begins in tobacco.

By eliminating the combustion in our system, the aerosol generated by heating the tobacco is fundamentally different to tobacco smoke. On average, it emits 90-95% less HPHCs compared to cigarette and no solid carbon-based nanoparticles. Several government authorities have tested the product independent of us, such us the U.S. Food and Drug Administration, the Japanese National Institute for Public Health, Public Health England amongst others, and they have verified that lower levels of HPHCs are emitted when heating tobacco instead of burning it.

But showing a reduce generation of toxic emissions is not enough. It is necessary to evaluate whether this reduced generation of HPHCs correlates to a reduce exposure in those adult smokers switching from smoking cigarettes to using heated tobacco products. At first sight, this seems straight forward: if there are less harmful compounds coming out of the heating tobacco system, why would not less toxicants enter the body?

But what we need to consider is that individuals use products differently. There are differences in how many times people use a product during the day, and on top, they can inhale shallow or deep, long or short among other variables.

We evaluated the exposure to several HPHCs in studies conducted in adult smokers not willing to quit. We divided smokers into three groups: the first one kept on smoking, the second stopped smoking for the duration of the study, and the third one switched to the tobacco heating system. Over a period of 90 days, we measured participant’s exposure to 15 selected harmful chemicals such as carbon monoxide, acrolein, and nitrosamines, among others.

As you can see in the following graphics, exposure to carbon monoxide and acrolein, for example, was significantly reduced in those subjects switching to heated tobacco (who are represented by the yellow lines) compared to those who kept smoking cigarettes (represented by red lines),

approaching to the values seen in those subjects who were in smoking abstinence (illustrated by green lines). The same findings were found for the 15 different HPHCs evaluated in this study. In all the cases, throughout the study the levels of exposure to the evaluated HPHCs in the subjects who switched to heated tobacco remained significantly below compared to those observed in smokers who continued smoking.

This study shows that switching completely to our heating tobacco system achieves almost 95% of the reduction in exposure that is achieved by smoking abstinence. Once again, several internationally recognized experts support our findings such us the U.S. Food and Drug Administration, the German Federal Institute for Risk Assessment, Public Health England among others.

And last, but not least, we evaluated the potential of switching to our heated tobacco system to reduce disease, which is the fourth component of the reduce risk term from the equation presented by Mikael.

Smoking-related diseases take a long time to develop, many variables are involved, and measuring any long-term effect will take decades. In the absence of long-term studies, we can still measure what happens along the disease pathway.

Toxicological assessment tells us about how much damage to the body of an organism the aerosol from heated tobacco may cause compared to cigarette smoke. And if that damage is likely to activate biological mechanisms, that may result in the onset of tobacco-related diseases.

Toxicity of heated tobacco aerosol exposure was evaluated in vitro studies: cytotoxicity and genotoxicity were significantly reduced compared to tobacco smoke and no mutagenicity was observed, showing that reduction in toxicity compare to cigarette smoke is in line with the 90-95% reduction in toxic emissions.

In vivo study conducted on Apoe-/- knock-out mice, a model that spontaneously develops atherosclerotic plaque and emphysema caused by its genetic alteration, showed that those individuals switched to heated tobacco (represented by yellow bars) reduced atherosclerotic plaque formation & emphysema development, compared to those exposed to tobacco smoke (illustrated by red bars). Also, the slow disease progression seen in those switched to heated tobacco aerosol approached the ones observed in those in smoking cessation (represented by green bars).

A clinical study conducted in 984 adult healthy smokers not willing to quit, who were randomly assigned to one of two arms: one who kept smoking cigarettes and another one who switched to heated tobacco. It showed favorable changes in those smokers who switched regarding the biomarkers of potential harm evaluated, which are linked to smoking related diseases, compared to those who continued smoking. Biomarkers of potential harms included were early signs of an increased risk of developing cardiovascular disease, cancer, or COPD.

Finally, we keep evaluating the risk profile of our heated tobacco product once it is commercialized. The first market where our product was launched in 2014 and where we have the broader experience in commercialization is Japan. In our first exploration of real-world data, looking at hospital records in that country, it was noticed that hospitalizations rate due to COPD exacerbations remained stable from year 2010 to 2016, and the same tendency was expected for the following years. However, after heated tobacco products became available, it could be observed a decline in the hospitalizations rate due to COPD exacerbations. Although smoking status is not well captured in hospital records, we see encouraging trends related to smoking-related diseases in our ecological study of hospitalizations in Japan. None the less, it has to be highlighted that to draw any conclusion or to establish a causal relationship, more research is needed.

Once again, several international regulatory bodies, such as the U.S. FDA, support that disease data take times, but more data across multiple lines of evidence are encouraging and warrant further research.

The totality of the available evidence today strongly indicates that switching to our heated tobacco system, although it is not risk free, is a much better alternative than continuing to smoke for those adult smokers who otherwise would keep smoking. For this to translate into a benefit for public health, we need to maximize the number of smokers who do not quit switching instead of continuing to smoke. And we must minimize unintended consequences of introducing an alternative, such as initiation or relapse.

In the next presentation, my colleague Steve will run you through our findings regarding product acceptance and use.

Thank you for joining us today and I'm looking forward to answering any questions you may have in our Q&A session.

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