Abstract
As part of emerging tobacco harm reduction strategies, modified risk tobacco products (MRTP) are being developed to offer alternatives that have the potential to reduce the individual risk and population harm compared with smoking cigarettes for adult smokers who want to continue using tobacco and nicotine products. MRTPs are defined as any tobacco products that are distributed for use to reduce harm or the risk of tobacco-related disease associated with commercially marketed tobacco products. One such candidate MRTP is the Tobacco Heating System (THS) 2.2, which does not burn tobacco but instead heats it, thus producing significantly reduced levels of harmful and potentially harmful constituents compared with cigarettes. The clinical assessment of candidate MRTPs requires the development of exposure-response markers to distinguish current smokers from either nonsmokers or former smokers with high specificity and sensitivity. Toward this end, a whole blood-derived gene signature was previously developed and reported. Four randomized, controlled, open-label, three-arm parallel group reduced exposure clinical studies have been conducted with subjects randomized to three arms: switching from cigarettes to THS 2.2, continuous use of cigarettes, or smoking abstinence. These clinical studies had an investigational period of 5 days in confinement, which was followed by an 85-day ambulatory period in two studies. Here we tested the previously developed blood-derived signature on the samples derived from those clinical studies. We showed that in all four studies, the signature scores were reduced consistently in subjects who either stopped smoking or switched to THS 2.2 compared with subjects who continued smoking cigarettes.
Highlights
Cigarette smoking is one of the leading causes of preventable human morbidity and mortality, causing serious diseases such as cardiovascular diseases, chronic obstructive pulmonary disease (COPD), and lung cancer
Exposure to nicotine and subjective effects related to smoking were assessed, and safety was monitored. These studies, conducted in Europe (ZRHR-REXC-03-EU) and Japan (ZRHR-REXC-04-JP), were registered on clinicaltrials.gov with the numbers NCT01959932 and NCT01970982, respectively. These studies demonstrated that the exposure to 15 harmful and potentially harmful constituents (HPHC) (Table 1) was significantly reduced upon switching from cigarette smoking to Tobacco Heating System (THS) 2.2 use, and that these reductions were of a similar magnitude than those observed in study participants who abstained from smoking for the duration of the study (Haziza et al, 2016a,b)
No serious adverse events related to THS 2.2 arms were reported and overall, the incidence of adverse events was comparable in the THS 2.2 and CC arms
Summary
Cigarette smoking is one of the leading causes of preventable human morbidity and mortality, causing serious diseases such as cardiovascular diseases, chronic obstructive pulmonary disease (COPD), and lung cancer. As noted by McNeil, “Since nicotine itself is not a highly hazardous drug, encouraging smokers to obtain nicotine from sources that do not involve tobacco combustion is a potential means to reduce the morbidity and mortality they sustain, without the need to overcome their addiction to nicotine” (McNeil, 2012). This new approach complements those aimed at reducing smoking prevalence and aims to provide smokers who do not quit with novel tobacco or nicotine-containing products that are substantially less toxic than cigarettes. The United States Family Smoking Prevention and Tobacco Control Act embraces the concept of THR and defines a modified risk tobacco product (MRTP) as any tobacco product that is sold or distributed for use to reduce harm or the risk of tobacco related disease associated with commercially marketed tobacco products (Luke et al, 2011)
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