Below is the transcript of the video:
Hello, my name is Christelle Haziza. I'm the Global Head of Clinical Research and Execution at Philip Morris. I'm very happy today to present you the approach we have used to assess tobacco harm reduction associated with THS use.
To date, there is no consensus on how to assess tobacco harm reduction in absence of large epidemiological data. The Institute of Medicines consider biomarkers of potential harm to be appropriate for estimating reduced risk for alternative products to cigarettes. Biomarkers are a measurement of an effect of exposure. They also include biological effects, alterations in morphology, structure, or function; clinical symptoms consistent with harm; and they can also include pre-clinical changes.
Today, I will present you our approach to assess tobacco harm reduction associated with THS, the tobacco heating system, based on biomarkers. In that context, multiple questions should be addressed, such as, what is the adherence to the new product under related exposure? How is the response to the biomarker in comparison to smoking cessation? What is the biomarker response in dual users?
To answer these questions, we designed an exposure response study that consisted in fact of two studies: one over six months and its six month extension. The study randomized a healthy smoker to continuing cigarettes or switching to the tobacco heating system. To compare the effect of tobacco heating system (THS) to that of cessation, we designed in parallel a smoking cessation study of one year. A set of biomarkers reported in the epidemiological studies to be sensitive to smoking cessation are linked to multiple aspects of pathogenesis related to CVD, COPD, and cancer was a priori selected and you can see it on the right graph.
These biomarkers were measured in the clinical studies at similar time points. When we look at the product use pattern, approximately 56% of subjects used more than 70% of THS over one year based on self-reporting. They smoke on average two cigarettes per day. We observed in 37 of dual users who smoke on average 9 cigarettes per day, the overall tobacco consumption did not increase from baseline. Looking at exposure to toxicants, the reduction in exposure was more pronounced in THS users than in dual users. Throughout the study, the biomarker response to THS followed the same direction as smoking cessation. The favorable effect was maintained over one year.
In the six-month study, we noted differences between THS use and cigarettes, which were statistically significant for five of them, as illustrated on the graph by the asterisk. Because of the limited accuracy of self-reporting, we analyzed the data according to quartiles of exposure to combustible cigarettes in THS users. We use CEMA as a biomarker of exposure to acrylonitrile. CEMA is a good marker to detect use of combustible tobacco products such as cigarettes. When looking at the magnitude of a favorable effect of THS per quartile of CEMA concentration, we observed that the lower the exposure to CEMA was, the higher the favorable effect was on biomarkers except for HDL.
Then, to contextualize our results, we compare the biomarker response to THS to that of smoking cessation, using the result of our smoking cessation study. THS users from the exposure response study were matched against quitters from the smoking cessation study at six months by propensity score analysis. The results are presented in the slide. Based on the self-reporting, the left graph, 50% of the effect of smoking cessation was observed for four of the biomarkers with THS use. Then in THS users, we analyzed the data excluding subjects who had the highest intensity of cigarette smoking by applying a cutoff CEMA concentration. Doing so, more than 67% of the effect of smoking cessation was observed for seven biomarkers with THS use.
The best option to reduce the risk for every smoker is definitively to quit. In the absence of epidemiological data, biomarker response provides relevant insight for evaluating tobacco harm reduction when evaluating alternative product such as THS. But it has to be evaluated in the context of smoking cessation. Dual users have less pronounced favorable effects, both in terms of exposure on biomarkers of potential harm than predominant switchers. Exclusion of the highest intensity of cigarette consumption in THS users by chemical verification showed that favorable response to THS corresponded to more than 67% of that of smoking cessation for seven of the biomarkers. Although addictive and not risk free, THS has the potential to reduce harm, as demonstrated by the totality of the robust scientific data available to date on THS.
Thank you so much for your attention.
Important: This presentation is for the purpose of publishing and disseminating scientific information about Philip Morris international’s efforts to develop and assess products that have the potential to reduce individual risk and population harm associated with tobacco use. This presentation is for audiences of scientists, public health and regulatory communities, and other stakeholders with an interest in tobacco policy. The purpose is not advertising or marketing. It is not intended for use by consumers.
Nothing in this presentation should be construed as making any representation, express or implied that the FDA has approved or has otherwise endorsed IQOS.