The Mesh of the Generics and the Potential of Emerging Therapies in the Smoking Cessation Market

Smoking is the leading preventable cause of death in the world. However, prior to 1900, tobacco smoking was an uncommon sight. It was not until the 20th century that smoking cigarettes became a routine or more precisely a popular trend among youths and adults. What helped in booming its adoption were effective advertising campaigns, standard cigarettes-making machines that would yield perfectly rolled cigarettes, and introduction of safety matches that contributed to the magnificent success of the tobacco industry. According to the CDC, in 2018, tobacco companies spent over USD 9 Billion in just promoting and marketing their cigars and cigarettes in the US. This means that the companies generating revenue out of their tobacco products are affluent enough to collectively spend USD 1 million every hour on advertising their products. 

From non-existent to a routine, then a trend, and over the time cigarette smoking became nothing but a nuisance that the whole world is fighting. However, it seems the mass-campaigns led by international organizations and non-profit organizations managed to evoke awareness among people. As per the recent WHO’s report (2000-25 third edition), overall global tobacco consumption sagged from 1.397 billion in 2000 to 1.337 billion in 2018. That is, approximately 60 million people steered away from tobacco use altogether. 

According to Creamer MR, Wang TW, Babb S, et al.,  approximately 55.1% of adult smokers that would be around 21.5 million people had attempted to quit smoking in 2017. However, around 7.5% of adult smokers (2.9 million) only managed to quit smoking successfully. So, what made it so hard? Nicotine. 

It is no rocket science, the nicotine, which is an active ingredient in tobacco, is a determinant of addiction. Thus, when a smoker decides to quit, s/he experiences withdrawal symptoms. Withdrawal symptoms range from craving due to nicotine-addiction, irritability, anxiety, difficulty concentrating, restlessness, decreased heart rate, and increased appetite or weight gain to more severe ones such as dysphoria, impatience, and insomnia. Fortunately, there exists FDA-approved therapies and drugs that double the success rates of quitting. 

Smoking Cessation: What are the drugs available in the market?

Quitting smoking is an arduous, exhausting process. However, it is possible. There are effective therapies and treatments that help to cease the use of tobacco. The USFDA’s Center for Drug Evaluation and Research regulates and ensures the safety and effectiveness of these products. Smoking Cessation treatment options involve both behavioral therapies as well as medications. There are 89 distinct products and services available today for Smoking Cessation, alongside 12 smoking alternatives that are not specifically indicated for cessation. Some of these approved products contain nicotine as an active ingredient, while others do not. 

FDA-approved pharmacotherapies includes Nicotine replacement therapy (NRT), which helps people quitting smoking to accustom themselves to specific amounts of nicotine via transdermal patch, gum, nasal spray, oral inhaler, and lozenges. The method helps people wean themselves into a routine which greatly works by gradually reducing the amount of nicotine. These are available as both over the counter and by prescription therapies.

Coming to the products FDA-approved, commercially available in the Smoking Cessation therapeutic market are Chantix (varenicline tartrate) and Zyban (buproprion hydrochloride). Both are available in tablet form and by prescription only. Chantix is also available in the EU and Japanese Smoking Cessation market. Whereas, Zyban is available in the EU and not in Japan. While Chantix works by acting on the active sites nicotine effects in the brain, thereby, shielding the so-called euphoric effects of nicotine, the exact mechanism of action of Zyban remains unclear; however, it can be more or less similar in lines of noradrenergic and/or dopaminergic mechanisms. Moreover, the generic drugs of Zyban are also approved, while for Chantix, its patent is soon going to expire in 2021 in the EU and in 2022 in Japan.

Generics in the Market

Whenever the branded drugs go off-the-market, it paves the way for the entry of generics in the market. Generic medications are the same as the original branded ones, but cheaper. In the Smoking Cessation market as well, there stands the generic of Zyban, that entered the market in 2006. 

However, the story of the generics of Zyban is a bit complicated. Here the generics in question are of the world’s leading developer of generics, Teva (and produced by Impax Pharmaceuticals). Two doses, bupropion XL 15 mg and bupropion XL 300 were approved. Since the higher dose was associated with the risks of seizures, the FDA granted a waiver in its testing. Rather, the bioequivalence studies were performed using the 150 mg strength; and the data was extrapolated to the higher dose. 

However, after their approval, the complaints of patients taking the generic higher dose having faced headache, GI disorder, fatigue and anxiety started to surface. Thus, finally, the USFDA announced the incoherency of the 300mg dose to deliver the key ingredient, thereby, its ineffectiveness in 2012. The good news—their 150mg dosage is still approved, which is pretty much clean in its records. 

Interestingly enough, there are other higher doses of generics of Zyban available in the Smoking Cessation market as well by Anchen, Actavis, Watson, and Mylan. The regulatory agency believed the results would be unique to Impax/Teva’s version, however, in a recent report, versions of Actavis, Inc., Mylan Inc., and Par Pharmaceutical came out to be therapeutically equivalent, while Watson’s version flopped. 

Smoking Cessation Emerging Therapies 

Besides the availability of pharmacological therapies, including branded as well as generics, non-pharmacological therapies such as individual or group counseling, and support to help smokers quit also appear to be effective. E-cigarettes are also a recently emerged trend in the Smoking Cessation market; however, their effectiveness and the severity of addiction remains debatable. 

Further, there are several unmet needs in the market ranging from the availability of only a few or limited non-nicotine therapies to a lack of societal and family support. Moreover, after on treatment regimen and quitting for weeks, or even months or years, there are cases of relapse. Nevertheless, many pharma and biotech companies worldwide are diligently working toward the development of novel treatment therapies with a considerable amount of success over the years. Key players, such as Axsome Therapeutics, Achieve Life Sciences, Chronic Airway Therapeutics, and several others are developing therapies for the treatment and trying to strengthen the girth of the Smoking Cessation market. Identification of new drug targets shall help the launch of novel therapies. DelveInsight estimates looking at the ongoing clinical activity, and an influx of pharma players to devote themselves to develop effective, non-nicotine therapies and also for relapsed cases, that the Smoking Cessation market size is expected to soar at a steady CAGR of 5.24% during the study period 2017-30 in the 7MM (the US, EU5 (the UK, Germany, Italy, France and Spain) and Japan). The emergence of potential pipeline therapies AXS-05 (Axsome Therapeutics), Cytisinicline (Axsome Therapeutics), Nadolol (INV102) (Chronic Airway Therapeutics), NFL-101 (Smoke Free Therapeutics/ NFL Biosciences SAS), and Liraglutide (Novo Nordisk) is expected to ease the global tobacco burden.  

AXS-05 is a novel, oral, investigational NMDA receptor antagonist with multimodal activity, and is in clinical development for major depressive disorder (MDD), Alzheimer’s disease (AD) agitation, and smoking cessation. The drug has shown a 25% greater reduction in average cigarettes per day for AXS-05 versus bupropion. Similarly, NFL-101, a patented, botanical drug candidate, aims at increasing the odds of quitting for smokers willing to quit. While Cytisinicline (also known as cytisine)—an established smoking cessation treatment—is an oral, plant-based alkaloid with a high binding affinity to the nicotinic acetylcholine receptor. Nadolol is used for the treatment of high blood pressure, migraine headaches, and chest pain. Thus, the Smoking Cessation pipeline paints an encouraging picture of the market landscape in the coming next decade. However, DelveInsight expects some hurdles making the growth pace a bit coarse. Strict pricing, reimbursement policies, as well as the arrival of the generics, are among the constraints that shall make the flow of the Smoking Cessation market size growth turbulent. Overall, the market growth is going to traverse steadily in the coming decade if everything goes as planned.