What is heat-not-burn?

The Science Behind Heat-Not-Burn

Philip Morris International has completed a broad range of laboratory and clinical studies on Tobacco Heating System (THS), a heat-not-burn tobacco product, as recommended by FDA’s Guidance. PMI filed an application with FDA in December 2016 seeking FDA review of the science presented herein and authorization to market THS in the U.S. as a Modified Risk Tobacco Product.

THS: Results Summary
Laboratory Studies

The levels of harmful or potentially harmful constituents (HPHCs) required to be reported to FDA were measured in the aerosol generated by THS and are over 90% lower, on average, than those in cigarette smoke from a 3R4F reference cigarette.1 Similarly, the levels of chemicals classified by the International Agency for Research on Cancer (IARC) as Group 1 carcinogens are reduced on average by more than 95% compared to a reference cigarette.

The table comparing the levels of HPHCs found in the aerosol of THS with the levels found in smoke from a reference cigarette based on analyses performed by Labstat International ULC, an independent contract research organization, is available here.

Table comparing the levels of HPHCs found in the aerosol of THS with the levels found in smoke

Toxicological studies conducted in laboratory models indicate that THS aerosol has the potential to be significantly less toxic than cigarette smoke. For example, in a long-term in vivo study designed to mimic the effect of switching from cigarette smoke to THS aerosol, the exposure to THS aerosol led to significantly reduced exposure to the HPHCs tested, as well as impact on biological mechanisms and disease endpoints associated with chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD).2

Disease Endpoint for COPD and CVD

Clinical Studies

Three-­month clinical trials recently carried out in the U.S. and Japan showed that smokers who switched to THS inhaled reduced levels of 15 harmful chemicals compared to smokers who continued to smoke. The reduction in exposure to HPHCs measured in smokers who switched to THS approached the effect observed in smokers who quit smoking for the duration of the study.

Overall, product satisfaction and measured nicotine uptake were comparable to a cigarette, indicating that THS may be a viable alternative for adult smokers. The chart below shows the results for four primary biomarkers of exposure to HPHCs.

 Chart on Primary Biomarkers of Exposure to HPHCs - Carbon Monoxide
 Chart on Primary Biomarkers of Exposure to HPHCs - Benzene
 Chart on Primary Biomarkers of Exposure to HPHCs - Acrolein
 Chart on Primary Biomarkers of Exposure to HPHCs - Butadine
Legend for Chart on Four Primary Biomarkers of Exposure to HPHCs.

The following chart shows the reduction in fifteen biomarkers of exposure to HPHCs:

Reduction in Biomarkers of Exposure After Switching for 3 Months

ClinicalTrials.gov Identifier: NCT01989156 | Results from a clinical trial conducted in the U.S. showing four biomarkers of exposure to HPHCs for adult smokers who continued to smoke, quit smoking, and switched to THS over a 5-day period in confinement followed by 85 days in an ambulatory setting.

Learn more about PMI’s clinical assessment program here.

Perception and Behavior Assessment

Premarket assessments show negligible interest in THS among adult never-smokers and former smokers. The assessments also showed substantial potential for full switching among adult smokers.

In one study conducted in the U.S., which tested a claim that switching completely from conventional cigarettes to THS can reduce the risks of tobacco-related diseases, 0% of never-smokers aged 18-­25 said they intended to use THS, while up to 39% of adult smokers stated a high intention to use the product.

Overall, premarket perception and behavior studies conducted in the U.S. consistently demonstrated that a significant percentage of adult smokers – between 20% and 39% – intended to use THS. This depended on the type of tested materials (i.e., information brochure, product packaging, or direct mail communication) and modified risk messages (e.g., a message that the product presents less risks of harm than continued smoking, a message that the product significantly reduces the exposure to harmful and potentially harmful chemicals). On the contrary, young adults (from legal smoking age, but minimum age of 18, to 25) who have never smoked showed virtually no interest in using THS. The data shows a range of interest between 0% and 1.1% within this sensitive section of the population, which should not be attracted to these types of products.

Premarket data is corroborated by the real-life results: In Japan, over 70% of users of THS (marketed outside the United States as IQOS) have fully switched to it as of December 2016. An additional 8% use THS predominantly (i.e., smokers who replaced 70-95% of their cigarette consumption with THS). In Italy, Switzerland, Russia, Portugal, and Romania, a full or predominant switching rate exceeded 60% among THS users. PMI estimates that over 1.5 million adult smokers have quit smoking and use THS exclusively.

The chart showing conversion rate in different countries:

Exclusive and Predominant User Share in Different Countries

Further, initial cross-­sectional population studies conducted in Japan and Italy suggest that THS generated negligible rates of initiation among adult never-smokers and relapse among adult former smokers (around 1%).

Learn more about PMI’s perception and behavior assessment here.

PMI is committed to transparent sharing of its candidate reduced risk product science for unbiased verification by qualified scientists. PMI’s clinical studies are registered on the U.S. National Institutes of Health website ClinicalTrials.gov. The results of PMI’s research are published in peer-reviewed publications: Since 2011, PMI has published over 160 peer-reviewed scientific articles and book chapters describing its approaches, methods and product assessment studies. PMI encourages other researchers to advance scientific and medical knowledge of products with reduced risk potential or verify PMI’s data through programs such as Investigator Initiated Studies or SBV Improver.

1. Average yield reductions of an investigational variant of THS compared to the 3R4F reference cigarette, calculated as an average of the reductions of individual HPHCs, which could be reliably quantified in the study. Aerosol was collected with Intense Health Canada’s Smoking Regime. All yields were taken on a mass-per-stick basis. Reduction calculations exclude nicotine.

2. Phillips et al., An 8-Month Systems Toxicology Inhalation/Cessation Study in Apoe-/- Mice to Investigate Cardiovascular and Respiratory Exposure Effects of a Candidate Modified Risk Tobacco Product, THS 2.2, Compared with Conventional Cigarettes. Toxicological Sciences 2016, 149(2):411-432. doi: 10.1093/toxsci/kfv243.

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