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1ONCOLOGY INDUSTRY ANALYSIS 1. 1Key trends and characteristics of Cytostatic industry ???high growth rate ??? higher propotion of the global pharma market in the years to come ???one of the fastest growing and most profitable therapeutic areas of the next few decades ???shift from accute cancer treatment to chronic disease management and prevention ???more and more biotech companies enter the market ??? connections with pharma to help through the maze of regulatory processes and clinical development ???patient advocacy programs . 2Opportunities of L therapeutic class to pharma companies ???large unmet medical needs – o5 mil new cases every year, second leading causes of dead oaccording to WHO 10 mil cases in 2000 and expected to grow to 14,7 mil within next 20 years ???low volume, high price ???small marketing resources (hospitals, tenders) ???significant off-label usage ???favoruable reimbursment environment ??? global healthcare expenditure for cancer exceed $110 bn 1. 3Oncology industry
The attraction of the cancer market to the pharmaceutical and biotechnology industry is as follows by Global Equity Research (Cancer, New Frontiers, UBS Warburg, October 2001): ? large unmet medical need ?low volume, high price ?small marketing resource ?small R&D expenditure ?significant off-label usage ?favourable reimbursement environment Global healthcare expenditures for cancer exceed $110 billion annually (for that round about 16 % get on anticancer pharmaceuticals), and every major pharma company is wing for position in that lucrative market, according to a eport by C. J. Sylvester, analyst for UBS Warburg. With the growth rate of over-65 populations outpacing other demographics, the ontology market can only escalate, especially as industry shifts focus from acute-care to chronic- disease management. Cancer will be the most critical and costly healthcare-management issue of the future, making the oncology market one of the fastest growing and most profitable therapeutic areas of the next few decades. It will also be one of the most challenging.
That challenge will come from a fundamental paradigm shift–from acute cancer treatment to chronic disease management and even prevention. Commercially, tomorrow’s global oncology leaders will not only look for ways to make current acute therapies better for patients, but they will also improve outcomes by targeting disease sites and holding cancer at bay at much earlier stages. That paradigm shift is also seen in the plethora of new pipeline products that are expected to be marketed in the next three to five years.
And, as more and more biotech companies enter the market, the fight to gain patient share will grow more intense. Key european trends Presumption: ?EU market integration, quicker launching new products into market ? Slower transition to “market driven” healthcare ?Growing HDP, low inflation ?Price influenced by regulation rules, generics and parallel sales ? Low advanced “consumable” approach to the healthcare 1. 3. 1. 1. 1Generic share and opportunity in cancer therapies The generic cancer market is small, both in terms of absolute size and penetration, compared to other therapeutic fields.
The principal reason for that are the limited number of cancer drugs that are off-patent, and combinations of other factors (e. g. difficulty in manufacturing) which constitute effective barriers to entry for generic companies with little experience in the cancer market. In most countries the cytotoxic and hormonal treatment segments contain a significant proportion of off-patent drugs mainly due to increased use of older drugs in combination therapies and the fact that new drugs offered only incremental improvements in effectiveness.
Furthermore, cytotoxic drugs are both difficult and expensive to produce. As a result there are relatively few companies marketing generic cytotoxic injectables compared to other therapeutic fields; the numbers of manufacturers is smaller still. Injactable cancer generics Two factors imply any company wishing to enter this market ???Expertise and investment in equipment are essential ???Wide portfolio of cancer drugs The generic injectables market has all the features of a niche market and is, therefore relatively insignificant in commercial terms.
As a result of nature of the market, prices of generic cancer drugs have not fallen to the same extent as those in other therapeutic fields. There is a little to indicate that this situation will change significantly over the next few years. Future development of the cancer generic market Dependent on several factors: ???an overall increase in the number of cancer patients ???launch of new products ???drugs coming off patent ???new regulation and policies introduced Taking all of this factors into account, the cancer generic market will continue to grow, both in terms of volume as well as in value.
CEE Products key drivers L01L02 199920022007199920022007 VinorelbineVinorelbineVinorelbineGoserelinGoserelinGoserelin CarboplatinDocetaxelDocetaxelMegestrolMegestrolAnastrozol PaclitaxelIrinotecanPaclitaxelLetrozolAnastrozolMegestrol DocetaxelPaclitaxelNCEAnastrozolLetrozolLetrozol Irinotecan NilutamidNilutamidNilutamid DoxorubicinNCE 1. 4Trends in Ca treatment ???New drug delivery systems in “old” drugs liposomes (doxorubicin, cytarabine), cyclodextrines inclusions (paclitaxel, cyclosporine), biopolymeric carriers (goserelin, leuprorelin, cisplatin), transdermal patches (fluorouracil, pain killers), Monoclonal antibodies ???Vaccines ???Gene therapy 1. 5Existing technologies ??? liquid injections ??? aqueous and non-aqueous solutions ??? freeze-dried injections ??? tablets ??? uncoated and coated (sugar /film coating aqueous solutions) ??? capsules ??? hard / soft ??? suspensions ??? solutions for local treatment ??? ointments 1. 6Future of existing technologies -improvement connected to safety handling during administration with cytostatic ( Monovial??, “Ready to use” injections, “double chamber” injections) -bi-layer tablets (mixing of two drugs with different release and pharmacological profiles) . 7The Future of Cancer Therapy – Cancer is a growing health problem not only for the US but also for other industrialised countries – increase in life expectancy around the world, coupled with growing urbanisation, industrialisation and changes in diets and lifestyles are leading to substantial increases in cancer rates globally – According WHO- 10 million cancers cases occurred around the world in 2000 and is expected to grow to 14,7 million cases within next 20 years In the next decade, clinical success will be built on recent scientific success – Cancer prevention, in the long term, will be achieved as pharmacogenomics, improved delivery systems, and new gene therapies converge in the next decade – In the near term, combination therapies will be the key to improved outcomes in cancer treatment – The decade promises significant strides in the development of targeted cancer therapeutics – As cancer therapy continues to evolve, pressure on the health care system and insurers is increasing in many question ( eg. ho will pay for these new therapeutics ) – Current technological advances are occurring within an environment increasingly pressured to respond to the growing number of elderly patients in the face of limited government and commercial funds – Despite the small overall percentage of the cost contribution of pharmaceuticals – ( about 10% of the total health care dollar ) – pharmaceuticals are often blamed for rising Health Care costs.
Health Care spending on pharmaceuticals is expected to rise to 15 – 20% by 2010 – The need for pharmacoeconomic studies will increase due to the resistance inherent among providers to accept new therapies only if they are proven to be both effective and cost – savings – With consumers feeling entitled to the best new treatments available, considerable pressure will be exerted by the public to adopt these therapies – It may be that customers will be willing to pay more for treatments that really work – to pay for quality – The risk to the health system and pharma companies providing new therapies will be legislation – Should governments decide to intervene in the treatment – selection process, whether motivated by ethics or cost – savings, access to good treatments could become curtailed more than 300 companies are reported to have approximately 1, 250 aggregate cancer drugs under development world wide ( gro of it in the in USA ) – 90% newly diagnosed cancers are solid tumors – Chemotherapy, surgery and radiotherapy most common forms of cancer treatment ( 800, 000 patients are on chemotherapy in US every year ) Cancer prevention – pharmacogenomics, improved delivery systems, and new gene therapies – raising outpatient and home treatments – $ 16Bn world wide anticancer market – will rise to $ 65bn until 2005 ( with new therapies ) – Screening the general population for cancer – genetic typing – future terapies – specifically designed for a particular patient The main activities in cancer – screening programme – register of cancer – cancer controls – Legislation – cancer patients assotiacions
Health Care will be deinstitunalised moving away from hospitals toward offices and home care – Health care is also beginning to be more uniform with the standardisation of data, diagnosis and treatments with clinical protocols, best practiceguidelines, and outcome – based decisions – biomedical advances will help more state -of-art health care beyond the traditional palliative drug treatment paradigm toward identifying and attaching the underlying mechanism of disease – customised care ( genetic and environmental origins of disease ) – gene therapies, cell based therapies, protein antibody drugs, site – selective targeting – from treatment towards prevention 1. 8Conclusions, Suggestions, Decision Making Background OpportunityNote, Suggested action, KSF Risks Generic applications/operations will be supported better by pharmaceutical legislation world-wide (“Bolar” provisions to come in the EU, filing during protection possible).
Note: Generic companies can save up to 2(3) years of the time to market. Compromise between innovative and generic companies will exists and will be balanced according to political situation. Suggested action: To utilise European resources in development process (political reason for introduction of “Bolar” provisions). To time submissions well. KSF: Fast and successful development processEconomic stagnation or down-turn anywhere may destabilise the EC and influence the mentioned balance. European resources, we “should” use, will be probably more expensive than the world average with variable quality. Any delay in the development process may have serious consequences.
Development resources should be optimised. Development process have to be started as early as possible to minimise chance to be late on the EC market. Harmonisation of legislation internationally (ICH) will continue. WHO will introduce common standards into developing countries. Note: Harmonised requirements minimise duplication of development work. It saves time and money. Common standards make penetration easier. Industry is a part of ICH process and can influence future trends. Suggested action: To be a part of ICH process. To file in countries where the harmonised legislation has been introduced (the same file to a country with removed barrier).
KSF: ICH adherenceHarmonised ICH guidelines are a matter of compromise, therefore we have to either influence process or monitor well to avoid too broad compromise to affect our interests badly. Countries may be keen on establishing extra barriers to “earn some money” from applicants. Any ICH non-compliance may have an impact. Harmonisation of legislation in Europe, an idea of a single market implemented even better and the single market biggerNote: Bigger market accessible by just one procedure. Regulatory requirements harmonised. CEE countries will turn to new EU members. Suggested action: To use MRP a much as possible. To utilise strong CEE position and turn it to a strong position in new member states. KSF: High MRP activity. Close co-operation with CEE regulatory agencies during harmonisation process. 0 new candidates have not agreed detailed approach to harmonisation of the content of dossiers of already registered products. The requirements may vary considerably requiring even more capacity and resources. It is absolutely necessary to reserve enough development capacity to assure that data can be generated either beforehand or on-request. MRP in new members may be very difficult to finalise effectively. Better definition of “public health concern”Note: Vague definition widely used by Member states to prevent direct mutual recognition. Better definition will result into less regulatory work dedicated to each member state and quicker approval. Suggested action: To time MRP well. KSF: Good dossiers. Proper selection of reference member state.
Even CTD-dossier on a very high level allows a big flexibility in rising “a public health concern” by Member states. A barrier, probably limited, will still exist. Selection of RMS will be critical to have well respected fist approval. CTD has been accepted. Will become obligatory on July 1, 2003Note: Harmonised requirements minimise multiplication of work. Suggested action: Information technology tools should be amended (Documentum) KSF: CDT implemented fully before the deadline expires. Sufficient investment into software and education is necessary. Any delay will mean serious barrier to file in any “regulated” market. Fast-track procedures and conditional approvals on Community level to be introduced for products of significant therapeutical interest.
Note: Has to do with better public health statement of the EU. Suggested action: To have product of that nature and use the procedures. KSF: Products allowed entering the procedures. An option for NCEs. Significant therapeutical interest has to demonstrated and that is not always possible at the time of the first submission. A big opportunity for competitors in the same therapeutical areas. Shortening of procedures planned. MRP facilitation planned. Note: Has to do with better public health statement of the EU. Suggested action: To use MRP facilitation measures. KSF: EU network present and developed. Better network is a considerable competitive advantage.
Mutual recognition of GMP audits planned. Note: FDA “extras” will be more difficult to impose into Europe. Suggested action: Proper audition strategy. To strengthen QA/QC position in the company. KSF: GMP adherence. Any “major” GMP, GLP or GCP non-compliance may have even catastrophic consequences. ThreatNote, Suggested action, KSFRisks Harmonisation of dossiers with the EU innovatorNote: Requirement has not been clearly defined yet. They will be highly probably country specific to a great extend. Suggested action: To monitor development of that. To reserve development capacity for products that have already been approved or are being approved. KSF: Proper monitoring.
Availability of resources. 10 new candidates have not agreed detailed approach to harmonisation of the content of dossiers of already registered products. The requirements may vary considerably requiring even more capacity and resources. It is absolutely necessary to reserve enough development capacity to assure that data can be generated either beforehand or on-request. Very extensive pharmacovigilance system (PS) replaces renewalsNote: Very costly (field force) and extremely time consuming to establish that. Suggested action: To establish world-wide PS. KSF: Early start, enough resources, robustness The system will be very probably inspected in the future.
Any major non-compliance may compromise existing marketing authorisations not only in the EC but also in the US as well. Availability of resources and co-operation of all representative offices are critical. Manufacturing sites of active substances and critical excipients will start to be inspected on regular basis by European bodiesNote: Some sites may not pass that successfully. Suggested action: To perform customer audits at the most important existing suppliers and to impose corrective actions, if needed. To select future suppliers strictly according to GMP level. To use PhEur certification procedure. KSF: GMP adherence. If only one supplier existed and it had failed to pass inspection whole logistic chain would collapse.
The risk should be splitted between more suppliers and we must perform customer audits at “critical” sites. QA/QC, purchasing, development and regulatory capacity needed. Good Clinical Practice directive to be implemented by 2004Note: Has to do with programme statement of EP. Suggested action: To implement that. KSF: GCP adherence. Only bioequivalence studies are performed now. Suitable certified CRO has to be hired. PMS studies (phase IV) will have to be a part of PS in the future. This function has to be established. FDA specific requirements Note: A kind of barrier. Suggested action: To introduce critical ones before FDA audit. KSF: FDA-GMP adherence. The risk is the they will continue to exist and even grow.