Technical Insights: Pharmaceutical Management of Obesity
Pharmaceutical Management of Obesity (Technical Insights) D2A1-TI March 2011
Table of Contents <ul><li>1. Executive Summary 1. Research Scope and Methodology 1. Research Scope and Segmentation 2. Research Methodology 2. Research Overview 1. Introduction to Obesity and Anti-Obesity Drugs 2. Key Findings and Analyst Insights 2. Technology Snapshot and Impact Analysis 1. Technology Snapshot 1. Anti-Obesity Drugs Classified on the Mode of Action 2. Value Chain for Anti-Obesity Drugs 2. Assessment of Factors Influencing Adoption of Anti-Obesity Drugs 1. Market Impact of Key Drivers 2. Impact of Key Challenges and Restraints 3. Regulatory Scenario 3. Diffusion of Innovations and Opportunity Evaluation 1. Diffusion of Innovation 1. Adoption of Anti-Obesity Drugs--North America 2. Adoption of Anti-Obesity Drugs--Europe and Asia Pacific 3. Overview of Partnerships and Alliances in the Industry 2. Opportunity Evaluation 1. Opportunity Strategy Evaluation of Anti-Obesity Drugs 2. Roadmap--Emerging Areas to Focus 4. Key Patents and Contacts 1. Key Patents 1. Issued Patents 2. Applied Patents 2. Contacts 1. Corporate Contacts 2. Academic Contacts </li></ul>
Key Findings <ul><ul><li>The number of FDA approved drugs is minimal only Alli (OTC), Xenical (prescription drug), and this market has witnessed a number of recent rejections by the FDA (for example, Contrave, Lorcaserin, Qnexa, and so on). Many drugs have been pulled off the market in the US and Europe, but generic versions are still used in many unregulated markets in Asian countries. </li></ul></ul><ul><ul><li>Inspite of many failures, companies are actively working on developing obesity drugs and a number of drug candidates in the pipeline (more than 30)--in early and late developmental stages. Other strategies, such as immunotherapy is also being developed, but currently in a nascent stage, </li></ul></ul><ul><ul><li>Many strategic alliances and partnerships has occurred in the last two to three years between companies and academia to advance obesity treatment by discovering new targets, unraveling metabolic networks, and furthering candidates in the later phases of development. </li></ul></ul><ul><ul><li>Safer alternatives, which are peripherally acting and have the same efficacy as surgical procedures are being developed, for example, polymer hydrogels, antisense drugs, nutraceuticals, targeted delivery, and so on. Pharmaceutical majors as well as SMEs developing innovative products in this area and the most innovative products are coming out of start-ups. </li></ul></ul><ul><ul><li>Heavy federal funding as well as VC funding in both EU and the US for obesity research and drug development has been observed in the last couple of years. </li></ul></ul><ul><ul><li>Funding in the APAC region is considerably lesser and though developments in APAC region is less in number, it is catching up with some research organizations working on high potential technology platforms. </li></ul></ul>
<ul><li>USA tops the obesity list with more than 30% of the population being obese and more than 70% overweight </li></ul><ul><li>Obesity rates in the UK are the highest in Europe and have increased significantly over the past few years. More than 20% of the population are now obese and the costs to the UK economy exceed £3 billion per year. </li></ul><ul><li>Obesity rates in Japan and Korea are among the lowest in the OECD, but have been increasing steadily. </li></ul><ul><li>India and China also have a small percentage of obese individuals, but considering the population, its is a potential market. China has more than 670 obese individuals. </li></ul><ul><li>More than half (60%) of Australian adults are either overweight or obese (Australian Bureau of Statistics) </li></ul><ul><li>Growing economies and changing lifestyle in the APAC region will eventually turn this region to be a hub for anti obesity products. </li></ul>Prevalence of Obesity in USA Source: Frost & Sullivan, 2011 Global Incidence of Obesity
Source: Frost & Sullivan, 2011 Anti-Obesity Drugs--Pipeline Mechanism of Action Company Details/Benefit of Product Phase of Development Appetite Suppressants/Satiety Inducers Neurosearch Tesofensine; centrally acting compound targeting multiple receptors in the brain- dopamine and serotonin, noradrenaline reuptake. No major benefits over other centrally acting drugs. Targeting three neuroatransmitters makes it little more effective than single receptor targeting drugs though; side effects are quite evident from trials Phase 2b 7TM Pharma Peripherally acting cannabinoid receptor antagonist(TM38837); Potentially safe when compared to centrally acting cannabinoid receptor antagonists which have serious neuropsychaitric efffects. Phase 2 Gelesis Inc Polymer hydrogel Attiva,which swells up in the GI tract and should have a quicker time to market compared to other drugs; safer alternative compared to other drugs acting via metabolic pathways Phase 1 Fat Absorption Inhibitors Alizyme Cetilistat is a lipase inhibitor, with a similar mode of action to Roche's anti-obesity medication orlistat (Xenical®) which received regulatory approval in 1997. Phase 3 Surface Logix Inc. SLX-4090; Enterocyte Specific Microsomal Triglyceride Transfer Protein Inhibitor. It blocking the chylomicrons in enterocytes, thereby reducing the uptake of triglycerides and cholesterol into systemic circulation. No systemic exposure or liver toxicity; inhibition is only in the gut. Phase 2b
Source: Frost & Sullivan, 2011 Anti-Obesity Drugs--Pipeline Mechanism of Action Company Details/Benefit of Product Phase of Development Fat Metabolism Enhancers Zafgen ZGN 433 ; Molecules directly target adipose tissue and fat metabolism. The lead compound is a methionine aminopeptidase 2 inhibitor, for treatment of severe obesity. Safety has been demonstrated in Phase1b studies. Efficacy is very high- almost matching that of surgical bariatric procedures Phase 2a (To be started later this year) Isis Pharmaceuticals Antisense compound targeting liver and fat tissue FGFR4(Fibroblast growth factor receptor). Targeted approach for fat burning and improving overall lipid metabolism. Combination therapy with appetite suppressors has shown positive results in animal models. IND Enabling Studies Avaxia Biologics Orally active antibodies for inhibition of sugar transporters in the GI tract. It is targeted against diabetes and obesity. No systemic exposure, not metabolized by gut enzymes. Sustained results with minimal immunogenicity. Preclinical Fat Mobilizers Ablaris Therapeutics The technology uses compounds to target blood vessels supplying to the white adipose tissue. The blood vessels targeting platform is broad and could lead to a large number of potential compounds, hence Ablaris is expected to have great flexibility in follow-on drug candidates. The compounds are administered via simple subcutaneous injection. Phase 1 (shortly)
Drivers Drivers Denotes Long term Impact Denotes Current Impact Increased incidence and awareness Number of companies working on different treatment approaches; Promising Pipeline Increase in partnerships and collaborations (both research and development phases) Source: Frost & Sullivan . 2011 Market Impact of Key Drivers Increase in Obesity Incidence Globally (Adult and Childhood Obesity) and Increase in Awareness; Market Impact: Short Term-High; Long Term-Very High Increases in obesity awareness and the risks of associated co-morbidities are making people opt for obesity therapies and treatment. People are not considering fat reduction for aesthetic and cosmetic reasons alone, but more for the serious health hazards it poses. Number of Companies Working on Different Treatment Approaches--Promising Pipeline; Market Impact: Short Term-Medium; Long Term-High Inspite of a number of failures and product recalls, there is still a good number of companies working on obesity drugs based on new targets and acting via peripheral mechanisms. More than 30 drugs are in Phase 1/2 development and approaches, such as vaccination, oral antibodies, and gene therapy are being developed as alternative, promising strategies. Combination therapies, which include two or more pharmacological agents and target multiple receptors and pathways can bring about a reduction in obesity more efficaciously. Increase in Partnerships and Collaborations (Both Research and Development Phases); Market Impact: Short Term-High; Long Term-High Alliances, partnerships, and collaborations between industry and academia for technology transfer, between large pharmaceutical companies, and small- and medium-sized innovative drug developers for development are many in number and sets the stage for further increases in investment and successful development of novel anti-obesity drugs.
Challenges and Restraints Competition from medical devices and surgical and cosmetic procedures Reimbursement issues Lack of efficacy coupled with serious side effects(High risk benefit ratio) Number of product withdrawals Strict regulatory norms Lack of multipronged targeting approach Impact of Key Challenges and Restraints Competition from Medical Devices and Surgical and Cosmetic Procedures; Short Term- Medium; Long Term- High Many devices and surgical procedures provide more sustained and effective results when compared to obesity drugs and many cosmetic procedures are preferred by patients due to compliance, overall costs, and safety issues. Lack of Efficacy/Serious Side Effects Sometimes Override the Positive Effects of the Drug; Short term- High; Long Term- Medium Most of the anti-obesity agents have modest efficacy in terms of weight loss and sustenance. Although some medications have been shown to significantly promote weight loss, their value lies in their ability to inhibit weight regain. Serious cardiovascular and neuro-psychiatric side effects are common with most of the centrally acting drugs and the weight loss caused by them is not significant when compared to the side effects. Reimbursement Issues; Short Term- Medium; Long term- Medium The poor reimbursement policies for obesity drugs has greatly limited its market potential. In most countries , OTC drugs are not reimbursed while only prescription drugs are. In many others obesity drugs are not even considered as a category for reimbursement. Lack of Multipronged Targeting Approach; Short term- Medium; Long Term- Low The obesity metabolic circuitry is complex and it is important to identify and target multiple targets involved with obesity rather than targeting one alone. It is important to target both the biological aspects as well as the psychological aspects of weight gain. Strict Regulatory Norms (Standards set by FDA and EMA); Short term- High; Long Term- Medium Sicne obesity drugs are considered more of a preventive therapy, it is very important for the drugs to have a low risk benefit ratio to be approved by regulatory agencies. Only two FDA approved drugs, Xenical (Roche) and Alli (GSK) are currently in the market. Many others, which were expected to enter the market by 2011 were rejected by the FDA panel. Number of Product Withdrawals; Short term- Medium; Long Term- Low The number of approved drugs for obesity has been steadily dropping and the number of drugs in the market currently is less than the number in 2005. The drugs sirbutramine, rimonabant sold under the names Meridia(Abbott), Accomplia (Sanofi Aventis) were pulled off the market in 2009 in the US, Europe, and most Asian countries. Both the drugs have serious side effects, which outweigh the positive effects of the drug.
Obesity Management Obesity Vaccine: Vaccination can provide a completely different paradigm of treating obesity and can be safer and produce more sustainable results compared to drugs and other procedures (Braasch Biotech developing a second generation Somatostatin vaccine). Gene Therapy- T his area has not seen too much of development, however it is of high interest and value as Obesity is a multigene disorder and development of gene therapy can provide a long term solution. Use of off label drugs for Obesity- Drugs used in the treatment of diabetes and many other diseases which have common pathways as that of obesity can be used as a potential treatment for obesity. These drugs have already undergone safety an efficacy trials and getting them approved for obesity treatment if relatively easier than working on new molecules. Peripherally Acting Drugs- Most of the currently used drugs act on the central nervous system and have serious cardiovascular and neuron side effects. Companies are trying to focus on peripherally acting drugs which are selective and specific and act only on the receptors on liver, gut and fat tissue without any effect on the heart and other central organs. Short-Term Long-Term Medium-Term Hormone mimetics and peptide drugs: Shift from small molecule drugs to peptides and hormones which are more biologically relevant and have a better mode of action. Nutraceuticals and Functional Foods: Better awareness and understanding of preventive healthcare has led to a market flooded with a n umber of herbal, nutraceutical and functional food based products. Eg, Dietary fibers, protein drinks, herbs (guggula) and so on. Source: Frost & Sullivan, 2011 Emerging Areas of Focus- Roadmap
Analyst Insights <ul><ul><li>APAC with its increasing prevalence in obesity and improvements in economy is a promising market and also a hub for contract research and manufacturing for obesity drugs. </li></ul></ul><ul><ul><li>Improving collaboration with academia and pharmaceutical/biotech companies globally will reinforce innovation in obesity drug development. </li></ul></ul><ul><ul><li>An increase in funding to develop new approaches to obesity treatment, such as gene therapy, immunotherapy, and so on, is likely to be seen in the near future. Companies are likely to invest in development of new drug targets and methods and concentrate on safer alternatives. Focus on development of new molecules, which act peripherally without having a negative effect on the central nervous system as well as cardiovascular system is likely to be a successful approach. </li></ul></ul><ul><ul><li>Companies should be on the lookout for potential markets and collaborate to develop on the marketing and distribution channels to gain worldwide acceptance for their drugs. </li></ul></ul><ul><ul><li>Clinical trial models to ensure better efficacy and less number of product failures need to be implemented. Pharmaceutical companies should focus on well defined clinical parameters and end points. </li></ul></ul><ul><li>With changes in regulations pertaining to nutraceutical and herbal formulations, it should become a more regulated market, which will make it more stringent and provide less competition to drugs than what is seen currently. </li></ul>