Pipeline and Commercial Insight: Nicotine Dependence - Chantix issues overshadow vaccine potential

Published by: Datamonitor

Published: Mar. 23, 2009 - 159 Pages

Table of Contents

ABOUT DATAMONITOR HEALTHCARE

About the Central Nervous System pharmaceutical analysis team

CHAPTER 1 EXECUTIVE SUMMARY

Scope of the analysis

Datamonitor insight into the nicotine dependence market

Key metrics

Related reports

CHAPTER 2 PATIENT POTENTIAL

Definition of nicotine dependence

The DSM-IV provides the most widely used definition of nicotine dependence

Diagnostic assessment tool characterizes level of dependence

Prevalence of tobacco smoking

Global number of smokers is expected to rise to 1.7 billion by 2025

Male smokers far outnumber their female counterparts in both developed and developing nations

Approximately 150 million people in the seven major markets are estimated to be current tobacco smokers

Prevalence of smoking in the US and UK has decreased steadily over the past decade

Smoking is less stigmatized in Germany and as a result rates have not fallen to the same extent as in the US and UK

Japanese men account for the highest seven major market smoking rate as antismoking legislations remain only loosely imposed

Smoking rates in developing nations are generally much higher than in developed countries

Significant smoking populations in BRIC nations represent substantial future market opportunity

GlaxoSmithKline targets multiple nicotine replacement therapy launches in emerging markets

Brazil - inspiring the world to quit smoking with shocking visual messages

Russia - female smoking rate rises but the government is now taking steps to combat smoking culture

India - smoking ban finally imposed in 2008 in a critical move to get the nation's estimated 120 million smokers to quit

China - accounts for almost one third of the world's entire smoking population

Global tobacco epidemic accounts for 5.4 million deaths annually

The World Health Organization's MPOWER policies are critical to helping reduce future tobacco-related illness and deaths in developing nations

The World Health Organization Framework Convention on Tobacco Control developed to counter the global tobacco epidemic

Epidemiology of nicotine dependence

Use of different criteria and methodologies limits study consistency

Risk factors for nicotine dependence

Genetic factors - susceptibility genes could lead to more tailored treatment

Psychiatric disorders increase likelihood of nicotine dependence and low quit rate success

Patient dynamics

Quit rate success is low with few individuals seeking help from their primary care physician or local services

UK quit rate dynamics - nicotine replacement therapies are used by the majority but National Health Service Stop Smoking Services rarely are

US quit rate dynamics - quit success rate stalls with more dependent smokers now remaining

French quit rate dynamics - historically, physicians have rarely motivated smokers to quit

Unmet needs in nicotine dependence

Reduction in relapse rate remains the primary clinical unmet need

Focusing on relapse prevention would be consistent with the chronic nature of nicotine dependence

Counseling platforms are essential to break the psychological dependence

Treatment duration is often too short for some patients

Chantix has demonstrated continuous abstinence through 24 weeks of treatment

Extended use of bupropion has been shown to delay relapse after smoking cessation

Need to increase presentation rates

Too few smokers accept that they would benefit from visiting a clinician in order to aid quitting

Lack of reimbursement and/or high cost of products is often a deterrent to quitting smoking

Medicaid coverage of recommended smoking cessation treatments has improved but is still not broad enough in many US states

Smoking cessation aids are sparsely covered by health insurance in Germany

Safety of smoking cessation therapies

Further research is required in specific patient populations for all smoking cessation therapies

Nicotine replacement therapies pose little risk to patients with cardiovascular diseases

Safety profiles of varenicline and bupropion have hindered their uptake

Nicotine replacement therapy options are still not broad enough

Products suffer from much slower onset of action compared to cigarettes

Rapid-acting gum or an improved nasal spray would be well-received by prescribers

CHAPTER 3 MARKET OVERVIEW

Market definition for this report

Treatment of nicotine dependence

Behavioral therapy

Telephone counseling - free expert advice anytime, anywhere

Internet-based programs - free information and extensive resources

Individual or group counseling programs - participants can share tips and advice

Nicotine replacement therapies

Nicotine patch (NicoDerm CQ, Nicorette, Habitrol/Nicotinell, Nicopatch)

Nicotine gum (Nicorette, NiQuitin, Nicotinell, Nicogum)

Nicotine lozenge (NiQuitin, Nicotinell, Nicopass)

Nicotine nasal spray and inhaler (Nicotrol/ Nicorette)

Approved non-nicotine containing medications

Bupropion (Zyban, Wellbutrin)

Varenicline (Chantix, Pfizer)

Clinical practice treatment guidelines

US Department of Health and Human Services

Ten key guideline recommendations call on all healthcare disciplines to work together

National Institute for Health and Clinical Excellence (NICE) published guidance

Recommendations aim to reduce health inequalities across social groups

Current market assessment

Prescription market sales dynamics

Rapid expansion of the prescription nicotine dependence market halts as market stabilizes out at $1.35 billion in 2008

The US remains the largest prescription nicotine dependence market despite a decline in 2008

Over-the-counter market sales dynamics

Over-the-counter nicotine dependence market value exceeds that of the prescription-derived market

Japanese and German over-the-counter nicotine dependence markets far exceed the prescription markets in each country

Future market assessment

The nicotine dependence market is forecast to grow strongly from 2009 to total over $3.82 billion in 2018

Three distinct phases will determine the prescription nicotine dependence market dynamics over the next 10 years

Key events in the forecast period - launch of two nicotine vaccines

Chantix (varenicline, Pfizer) - key marketed brand overview

Drug overview

Novel smoking cessation therapy launched in the US and UK during 2006

Combination of agonist and antagonist effects in smoking cessation

The UK's National Institute for Health and Clinical Excellence was quick to recognize Chantix's cost-effectiveness

'GETQUIT Support Plan' aims to improve compliance

Additional studies resulted in Japanese approval

Brand dynamics

Pfizer updates Chantix label to warn of risk for increased suicidal ideation

US sales negatively impacted by January 2008 label update

Tortoise and hare direct-to-consumer advertising campaign relaunched in September 2008

Expert opinion

Opinion leaders remain unanimously positive over Chantix's safety profile

Improved follow-up will be essential to re-establish brand confidence

Post-marketing studies in a range of patient subgroups will help to establish the truth behind the safety warnings

Real-world data analysis shows effectiveness of Chantix when combined with behavioral counseling

Forecasts to 2018

Base seven major market forecast - Chantix sales rebound in coming years

Scenario forecast in the US - Safety fears continue to hamper Chantix sales

Drug assessment

Chantix remains the most attractive approved nicotine dependence therapy

Clinical trial data - studies showed 44% of Chantix users remained abstinent during weeks 9-12 of treatment

Large Phase II study showed impressive continuous abstinence rates through 12 weeks

Phase III comparative trials demonstrated superior efficacy of Chantix versus bupropion and placebo

Post-treatment follow-up exhibited long-term abstinence of Chantix-treated patients

CHAPTER 4 PIPELINE OVERVIEW AND R&D DYNAMICS

Pipeline overview

Few companies appear willing to seize the opportunity in the vast nicotine dependence market

Vaccine products remain a key focus in the nicotine dependence pipeline

Four nicotine vaccines are now in clinical trials to treat nicotine dependence

A vaccine for the treatment of nicotine dependence would present many commercial advantages over current approaches

Nicotine vaccines have the potential for prophylactic use

Relapse prevention as a conceivable target indication for pipeline agents

Greatest promise for a nicotine vaccine may not be in smoking cessation but as a relapse-prevention tool

Market potential for a relapse prevention therapy will depend on patient perception

Discontinued or on-hold projects

Sanofi-Aventis - three late-stage development discontinuations scupper plans to expand into nicotine dependence market

Dianicline - project terminated as not adequately differentiated from Chantix

Surinabant - development discontinuation announced in October 2008

Rimonabant - FDA non-approvable letter for smoking cessation in February 2006

Nalmefene (Somaxon) - development program 'on hold' following unsuccessful Phase II/III study in pathological gambling

Positive Phase II results for the opioid antagonist in smoking cessation

Clinical trial design in nicotine dependence

Recommended measures to assess efficacy

Primary endpoint should measure abstinence out to at least 1 year after drug treatment

Secondary endpoints should include shorter abstinence measures and place an importance on assessments of withdrawal symptoms

Patient populations

Inclusion criteria require participants to smoke 10 or more cigarettes per day

Opinion leaders recommend inclusion of more heterogeneous participant samples

Relapse prevention study designs

Clinical trials incorporate two phases and a long-term follow-up to assess continued abstinence

CHAPTER 5 LATE-STAGE DRUG ANALYSIS AND FORECASTS

Key late-stage pipeline summary

Comparative forecasts

Comparative drug assessment

NicVAX (Nabi Biopharmaceuticals)

Drug overview

Fast Track status and agreed Special Protocol Assessment yet development partner remains elusive

Forecasts to 2017

NicVAX forecast to become the first vaccine approved for nicotine dependence

Development partner is essential for NicVAX to realize its market potential

Datamonitor drug assessment summary

Clinical positioning makes NicVAX an attractive licensing proposition

Marketing factors

Commercialization partner imperative for Nabi to compete effectively with Novartis and Cytos

As the first nicotine vaccine NicVAX will generate strong interest among physicians, patients and the general public

Patient potential

Individual variability in immunological response is a limiting factor

Satisfaction of unmet needs

Therapeutic response comparable to Chantix despite no use of behavioral counseling

Although an injection, convenient dosing regimen will increase compliance

Long-term presence of antibodies should reduce relapse rate

Favorable side-effect profile anticipated as NicVAX does not work centrally

Clinical trial data

Positive Phase II immunogenicity study results show increased antibody response with a more regular dosing schedule

One-year Phase IIb proof-of-concept study provides foundations for larger Phase III program

NIC-002 (Novartis and Cytos Biotechnology)

Drug overview

Secure Novartis licensing agreement offsets trailing development status compared to NicVAX

Forecasts to 2017

NIC-002 launch expected to trail NicVAX by a year

Datamonitor drug assessment summary

Novartis's CNS and vaccine experience greatly improves NIC-002's commercial attractiveness

Marketing factors

Novartis's marketing and sales experience bodes well for the launch of NIC-002

Second-to-market vaccine for nicotine dependence

Patient potential

Varied immunological response will restrict patient potential

Satisfaction of unmet needs

Impressive continuous abstinence only shown in high antibody level responders

Convenient dosing regimen will increase compliance

Long-term irreversibility of NIC-002 will reduce relapse rate

Favorable side-effect profile shown with new formulation

Clinical trial data

New Phase II study designed to assess efficacy of high nicotine antibody titers

Dose, regimen and formulation optimization studies essential to produce the best possible product for late-stage trials

Positive Phase II study results obtained through reanalysis of high antibody level responders

Unforecasted pipeline drugs

TA-NIC (Celtic Pharma)

'Rapid' enrollment completed in Phase IIb smoking cessation trial of TA-NIC

Celtic plans to outlicense TA-NIC after Phase IIb trial

GW-468816 (GlaxoSmithKline)

Product initially entered Phase II trials for smoking cessation over 5 years ago

Preclinical studies suggest NMDA receptor antagonists may have a potential role in nicotine dependence

Ongoing Phase II study assesses prevention of relapse in recently quit female smokers

EVT-302 (Evotec)

Exploratory Phase II craving study results announced in September 2008

Proof-of-concept Phase II quit-rate study initiated in September 2008

Studies of selegiline support hypothesis for using monoamine oxidase B inhibitors as smoking cessation therapy

Niccine (Independent Pharmaceutica AB)

Intramuscular vaccine primarily targeting the prevention of smoking relapse

Nicotine carrier protein selected to maximize the selectivity of the generated antibodies

Enrollment completed in relapse-prevention Phase II Scandinavian trial

ARD1600 (Aradigm)

Inhaled nicotine product to address acute craving for cigarettes

Phase I data show rapid achievement of comparative blood nicotine levels

Nicotine MDTS (Acrux)

Transdermal spray formulation of nicotine designed to combat the irritation often experienced with patches

QuitPak/INT003 (Cary Pharmaceuticals and IntelGenx)

Combination of mecamylamine and bupropion to work in synergy for overall smoking cessation goal

Phase I pharmacokinetic study shows sustained-release QuitPak is suitable for once-daily dosing

BIBLIOGRAPHY

Journal papers, books, and conference abstracts

Websites

Datamonitor reports

APPENDIX A

Data definitions, limitations and assumptions

Standard units

Japanese market data

Estimated 2008 sales revenue

Derivation of sales forecasts and pricing trends

Methodology

Indication-specific sales calculations

Forecast sanity checking - parallel patient population dynamics assessment

APPENDIX B

Contributing experts

About Datamonitor

About Datamonitor Healthcare

About the Disease analysis team

Disclaimer

List of Tables

Table 1: DSM-IV criteria for nicotine dependence

Table 2: Fagerström Test for Nicotine Dependence

Table 3: Adult prevalence of tobacco smoking (%) across the seven major markets as reported by the World Health Organization, 2008

Table 4: Current tobacco smoking prevalence in the seven major markets, 2008

Table 5: Adult prevalence of tobacco smoking (%) in Brazil, Russia, India and China, 2001-06

Table 6: Results of epidemiology studies of nicotine dependence across the seven major markets

Table 7: Key nicotine replacement therapies, 2008

Table 8: Prescription sales and growth dynamics of the key nicotine dependence products in the seven major markets, 2004-07

Table 9: Datamonitor's estimated launch dates for prescription nicotine dependence products across the US, 5EU and Japan, 2009-2018

Table 10: Chantix: key facts, 2009

Table 11: Percentage of continuous abstinence from cigarette smoking at weeks 9-12 across three key clinical trials

Table 12: Percentage of continuous abstinence from cigarette smoking at weeks 9-52 across three key clinical trials

Table 13: R&D pipeline in nicotine dependence, February 2009

Table 14: Discontinued or on-hold nicotine dependence projects, February 2009

Table 15: Forecasted late-stage pipeline nicotine dependence developments, 2008

Table 16: Key factors impacting on the revenues of NicVAX, 2009-2018

Table 17: 12-month continuous abstinence results from NicVAX Phase IIb study

Table 18: Key factors impacting on the revenues of NIC-002, 2009-2018

Table 19: Continuous abstinence levels with NIC-002 at 6 and 12 months after start of treatment

Table 20: Datamonitor drug assessment parameters for nicotine dependence products, 2009

Table 21: Parallel forecast patient population dynamics assessment for the US prescription nicotine dependence market, 2007-2018

List of Figures

Figure 1: Historical (2007-08) and forecast (2009-2018) prescription-based nicotine dependence sales revenue ($) for key marketed and pipeline products across the seven major markets

Figure 2: Prevalence of current tobacco use in adults in top-27 countries

Figure 3: Adult prevalence of current tobacco smoking (%) across the seven major markets as reported by the World Health Organization, 2008

Figure 4: Prevalence of current smoking among adults aged 18 years and over in the US, 1997-June 2008

Figure 5: Prevalence of current smoking among adults aged 16 years and over in the UK by gender, 1998-2006

Figure 6: People setting a quit date through the National Health Service by pharmacotherapy received in England, 2007-08

Figure 7: Percentage of successful quitters by type of pharmacotherapy received in England through the National Health Service, 2007-08

Figure 8: Unmet needs in the treatment of nicotine dependence, 2009

Figure 9: Maintenance of abstinence with Chantix (varenicline, Pfizer) in a 52-week clinical trial

Figure 10: Plasma nicotine levels (nicotine replacement therapies and cigarette) over 30 minutes

Figure 11: Seven major market prescription nicotine dependence market value ($m) by molecule, 2004-08

Figure 12: Prescription nicotine dependence market value ($m) by country in the seven major markets, 2004-08

Figure 13: Sales revenue of over-the-counter nicotine replacement therapies across the seven major markets ($m), 2004-08

Figure 14: Regional sales of the nicotine dependence market split by prescription and over-the-counter revenues across the seven major markets ($m), 2007

Figure 15: Prescription nicotine dependence market sales forecast ($ billion) by seven major market region, 2007-2018

Figure 16: Mechanism of action of varenicline (Chantix, Pfizer)

Figure 17: Major events in the marketed lifecycle of Chantix (varenicline, Pfizer), 2006-09

Figure 18: Chantix (varenicline) quarterly US and international sales ($m) dynamics, Q3 2006-Q4 2008

Figure 19: Datamonitor's sales forecast ($m) of Chantix (varenicline, Pfizer) across the seven major markets, 2007-2018

Figure 20: Sales ($m) forecast dynamics of the two scenarios regarding Chantix's (varenicline, Pfizer) future in the US, 2007-2018

Figure 21: Sales ($m) forecast dynamics of the US prescription nicotine dependence market according to two scenarios for Chantix's (varenicline, Pfizer) future, 2007-2018

Figure 22: Datamonitor's drug assessment summary for Chantix in the nicotine dependence market in the seven major markets, 2009

Figure 23: Smoking relapse prevention study designs

Figure 24: Datamonitor's competitive positioning analysis of pipeline products in development for nicotine dependence in the seven major markets over the forecast period, 2009-2018

Figure 25: Datamonitor's sales forecast ($m) for NicVAX (Nabi) for nicotine dependence across the seven major markets, 2009-2018

Figure 26: Datamonitor's drug assessment summary for NicVAX in the nicotine dependence market, 2009

Figure 27: NicVAX Phase IIb proof-of-concept trial design

Figure 28: Datamonitor's sales forecast ($m) for NIC-002 (Novartis and Cytos) for nicotine dependence across the seven major markets, 2009-2018

Figure 29: Datamonitor's drug assessment summary for NIC-002 in the nicotine dependence market, 2009

Figure 30: Datamonitor's nicotine dependence market forecast sanity check methodology

Abstract

• Patient potential analysis across the seven major markets, Brazil, Russia, India, and China as well as assessment of clinical unmet needs.
• Analysis of the prescription and over-the-counter pharmaceutical markets for anti-smoking products from 20042008 in the seven major regions.
• Case study review of Chantix including historic sales data analysis, opinion leader view on its safety and prospects, with scenario forecasts to 2018.
• In depth pipeline analysis, with detailed profiles of late-stage nicotine vaccines that feed into a region-specific market projection to 2018.

• Appreciate the nicotine dependence patient potential and where future geographical market opportunities exist.
• Benchmark key late-stage pipeline nicotine dependence projects against current market leading brands, supported by insight from key opinion leaders.
• Quantify the future market landscape with sales forecasts of marketed, generics, and key late-stage pipeline drugs to 2018 in the US, 5EU and Japan.

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