Thirty-first Session of WHO South-East Asia Advisory Committee on Health Research, 21-23 July 2009, Kathmandu, Nepal AgendaAgenda 3.1.33.1.3 FollowFollow upup ActionsActions ofof 30th30th SEASEA--ACHR:ACHR: PromotionPromotion ofof ResearchResearch andand DevelopmentDevelopment onon DrugsDrugs andand VaccinesVaccines N.K. Ganguly Distinguished Biotechnology Fellow & Advisor Translational Health Science and Technology Institute National Institute of Immunology New Delhi OutlineOutline ofof TalkTalk zExisting facilities & strengths zChallenges zThe way forward Thailand Indonesia R&D Facilities for Drugs & Vaccines in SEAR Korea Bangladesh India DrugsDrugs && VaccinesVaccines :: R&DR&D FacilitiesFacilities z Thailand z US Military HIV Research Program z Vaccine Trial Center z Mahidol University z Indonesia z Bio Farma z South Korea z The International Vaccine Institute z LG Life Sciences Ltd. z Crucell / Berna Biotech Korea Corp. z India z Various organizations MajorMajor R&DR&D FacilitiesFacilities :: IndiaIndia z Public Sector z Private Sector z Indian z Serum Institute of Immunologicals Ltd. India Ltd. z Panacea Biotech z Bharat Ltd. Immunologicals & z Bharat Biotech Biologicals Corp. International Ltd. Ltd. z Biological E. Ltd. z Central Drug z Shantha Research Institute Biotechnics Ltd. z Haffkine Bio- z Zydus Cadila Pharmaceutical z Cipla Corp. Ltd. z Ranbaxy Anti-tuberculosis drugs Anti-diabetic Anti-malarial agents drugs Anti-cancer Anti-HIV drugs drugs Anti- Cholesterol- Dyslipidemic lowering drugs agents Oseltamivir INDIND moleculesmolecules inin clinicalclinical trialstrials inin IndiaIndia Organizations IND molecules CDRI, Lucknow Anti-hyperglycaemic agent DRDO, New Delhi Adjuvant in the radiotherapy of cerebral glioma patients Ranbaxy, New Delhi For treatment of overactive bladder and urinary incontinence Ranbaxy, New Delhi Anti-microbial agent Ranbaxy, New Delhi For treatment of benign prostatic hyperplasia Wockhardt Ltd., Mumbai Antibacterial agent Dr.Reddy’s Lab., Hyderabad Anticancer agent Lupin Ltd, Mumbai Nasal formulation for migraine Lupin Ltd., Mumbai Herbal preparation for psoriasis Lupin Ltd., Mumbai Anti-tuberculosis agent Sun Pharma, Baroda Anti-histaminic agent Malladi, Chennai Thrombolytic agent Dr.Reddy’s Lab., Hyderabad Dyslipidemic agent Zydus Cadila, Ahmedabad Dyslipidemic agent Drugs Testing Educational & Research Medical Colleges Laboratories Institutes & Hospitals Bio-Safety Transgenic Level 2, 3, 4 Animal Facilities Facility Human CROs Resource Clinical National Trial Ethical / Centres Regulatory Guidelines Indian Pharma National Animal Toxicology Research Industry Resource Facility Centres TopTop tenten pharmaceuticalpharmaceutical companiescompanies inin IndiaIndia :: revenuerevenue growthgrowth raterate inin 20072007 Company Revenue growth Ranbaxy INR 42 billion Dr. Reddy’s Laboratories INR 42 billion Cipla INR 38 billion Sun Pharma Industries INR 25 billion Lupin Labs INR 22 billion Aurobindo Pharma INR 21 billion Glaxo Smith Kline Pharma INR 18 billion Cadila Health Care INR 17 billion Aventis Pharma INR 10 billion Ipca Laboratories INR 10 billion WHOWHO prequalifiedprequalified drugsdrugs fromfrom thethe SEARSEAR z 87% of drugs manufactured in the SEAR that attain WHO prequalification are manufactured in India. z HIV / AIDS Drugs (single & combo) : 93 z Tuberculosis Drugs (single & combo) : 17 z Anti-Malarial Drugs (single & combo) : 5 ChallengesChallenges z Slowdown in pharmaceutical innovation after 2000. z Escalating costs and prolonged time taken to develop new drugs. z Stringent regulatory focus on drug safety. z A single drug development process takes over USD 1.2 billion investment. z A single vaccine development process takes over USD 0.5 billion investment. DrugDrug developmentdevelopment pathwaypathway Phase III Phase I 250-4000 more varied patient groups 20-50 healthy volunteers to – to determine short-term safety and gather preliminary data efficacy Animal Phase II experiments for ADME-TOX 150-350 subjects Phase IV studies, with disease – to carcinogenicity, determine safety Post-approval mutagenicity / and dosage studies to teratogenicity recommendations determine specific safety issues Preclinical Phase IV : Post development Phase I Phase II Phase III marketing surveillance Single drug : USD 1.2 billion investment !!! Registration Development Post Registration VaccineVaccine developmentdevelopment pathwaypathway Laboratory Technology GMP grade development transfer material Preclinical toxicity USD 0.5 billion !!! Phase I trial No Go Phase II trial No Go Phase III trial No Go Production No Go Post-marketing surveillance further adds to the cost ! Access Treatment costs Drug financing CHALLENGES Public funding Antimicrobial Global trade resistance TheThe WayWay ForwardForward NeglectedNeglected DiseasesDiseases :: AA HighHigh PriorityPriority forfor thethe SEARSEAR z Drugs for Neglected Diseases Initiative (DNDi) set up in 2003 to tackle specifically the issue of neglected diseases. z Scientific Advisory Group on Tropical Diseases was established by WHO. z Focus on drug development efforts for : z Soil transmitted Helminthiasis z Leishmaniasis – Drawbacks of Miltefosine. Need for cheaper AmBisome z Need for more antimalarials PromotingPromoting R&DR&D inin DrugsDrugs :: RoleRole ofof CollaborativeCollaborative NetworksNetworks z DNDi : Anti-leishmania combos (DNDi & ICMR collaboration) z Ambisome + Paramomycin Amphotericin B z Ambisome + Miltefosin Vs z Paramomycin + Miltefosin deoxycholate (the standard) Complete report will be available in 2010 z Stop TB partnership : Established in 2000 to realize the goal of eliminating TB – vision for a TB free world. z TB Alliance : Development of new affordable TB drugs for short treatment time, activity against MDR-TB, compatibility with HIV anti-retrovirals. Mainly funded by B&M Gates Foundation, Govts of USA, UK and the Netherlands. TacklingTackling AntibioticAntibiotic ResistanceResistance :: RISHIRISHI ChembiotekChembiotek ClininventClininvent DrugDrug DiscoveryDiscovery InitiativeInitiative z Application of genomics technologies to develop new antimicrobial compounds against essential proteins in bacteria. z Targeting 6 essential enzymes involved in bacterial cell wall synthesis. z Novel way of tackling multi-drug resistant bacterial infections since it will be extremely difficult for bacteria to develop resistance to critical house-keeping proteins. PromotingPromoting moremore clinicalclinical trialstrials inin thethe SEARSEAR The SEAR countries are conducive for clinical trials… z Low cost for clinical trial implementation. z Genetically diverse population. z Faster regulatory approvals. z Presence of pharmaceutical know-how and well trained technical personnel. z High quality clinical trial set-up. z More clinical trials translates into more opportunities for manufacture of generic drugs. PromotingPromoting ManufactureManufacture andand UptakeUptake ofof GenericGeneric DrugsDrugs An important way of reducing cost and increasing access to life-saving drugs. z Generic versions of drugs are 30-80% cheaper than the branded product. z Generic versions can be manufactured legally when the drug is off-patent. z Generic versions can be produced as “approved generics” with license from the manufacturer of the parent drug. z Generic versions can be legally manufactured in countries that take part in clinical trials of the original drug. PromotingPromoting BiosimilarsBiosimilars z OverOver 60%60% ofof thethe toptop playersplayers inin thethe globalglobal biosimilarsbiosimilars marketmarket areare basedbased inin thethe SEAR.SEAR. z TopTop companiescompanies workingworking onon BiosimilarsBiosimilars –– Biocon,Biocon, Bioton,Bioton, EmcureEmcure (Gennova),(Gennova), Hospira,Hospira, Intas,Intas, BioBio Farma,Farma, LGLG LifeLife Sciences,Sciences, NovartisNovartis (Sandoz),(Sandoz), Ranbaxy,Ranbaxy, Teva,Teva, andand Wockhardt.Wockhardt. z ElaximElaxim (Tenecteplase)(Tenecteplase) andand erythropoietin,erythropoietin, manufacturedmanufactured byby Gennova,Gennova, havehave beenbeen approvedapproved byby thethe USFDA.USFDA. Source : Business Insights, May 2009 RecombinantRecombinant therapeutictherapeutic drugsdrugs approvedapproved forfor marketingmarketing inin IndiaIndia Molecules Therapeutic applications Hepatitis B vaccine (r- HBsAg based) Immunization against Hepatitis B virus Erythropoietin Treatment of anemia Interferon alpha 2B Treatment of leukemia, Hepatitis B and Hepatitis C Epidermal Growth factor (EGF) Organ morphogenesis and mitogenesis Streptokinase Dissolution of clot in acute myocardial infarction Human insulin Treatment of diabetes GM-CSF; G-CSF Treatment of chemotherapy induced neutropenia; treatment of neutropenia Interferon alpha 2A Chronic myeloid leukemia Human growth hormone Treatment of dwarfism in children Nimotuzumab Treatment of breast cancer Rituximab Treating non-Hodgkin’s lymphoma & arthritis. Tissue Plasminogen Activator Dissolution of clot in acute myocardial infarction Blood factor VIII Treatment of hemophilia type A Follicle stimulating hormone Treatment of reproductive disorders Teriparatide (Forteo) Parathyroid hormone for treating osteoporosis Drerecogin alpha (Xigris) Burns and severe sepsis Platelet Derived Growth Factor (PDGF) Receptor antagonist in certain types of cancer Interleukin 2; interleukin 11 Treatment of renal cell carcinoma; treatment of thrombocytopenia Blood factor VII (Eptacogalpha) To control bleeding in hemophilia patients Interferon gamma To treat chronic granulomatous disease