1 / 48

Drug Developments in 2010

Drug Developments in 2010. Implications for the Pharmacy Purchaser Kevin Hoehn PharmD MBA Faxton-St. Luke’s Healthcare Utica NY.

leanna
Download Presentation

Drug Developments in 2010

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Drug Developments in 2010 Implications for the Pharmacy Purchaser Kevin Hoehn PharmD MBA Faxton-St. Luke’s Healthcare Utica NY

  2. Annual Growth in Drug Expenditures 1998-2009Diamond=total expenditures Squares=expenditures for nonfederal hospitals triangles=expenditures for clinicsAJHP Vol 67, 2010 e4 Figure 1

  3. Total Numbers of Drug Shortages and Shortages Involving Injectable Drugs in the United States 2005-2009 NEJM June 16 2010 (ahead of print) Jensen V and Rappaport B 2010; 2010:1056

  4. Drug Development Process • It takes 12 years on average for an experimental drug to travel from laboratory to medicine cabinet • Only five in 5,000 compounds that enter preclinical testing make it to human testing • One of these five tested in humans is approved

  5. Preclinical Testing • A pharmaceutical company conducts laboratory and animal studies to show biological activity of the compound against the targeted disease, and the compound is evaluated for safety. These tests take approximately three and one-half years.

  6. IND versus NDA • Investigational New Drug Application (IND) • After preclinical testing, the company files an IND with the FDA to begin to test the drug in people • Shows results of previous experiments, chemical structure of the compound; how thought to work in the body; toxic effects found in the animal studies • Reviewed and approved by the Institutional Review Board. Progress reports on clinical trials must be submitted at least annually to the FDA

  7. IND versus NDA • New Drug Application (NDA) • After completing all phases of clinical trials, the company analyzes the data and files an NDA with the FDA if the data successfully demonstrates safety and effectiveness • Must contain all of the scientific information that the company has gathered • Typically run 100,000 pages or more • The average NDA review time for new molecular entities approved in 1992 was 29.9 months

  8. Clinical Trial Phase I • These tests take about a year and involve about 20 to 80 normal, healthy volunteers. The tests study a drug's safety profile, including the safe dosage range. The studies also determine how a drug is absorbed, distributed, metabolized and excreted, as well as the duration of its action.

  9. Clinical Trial Phase II • In this phase, controlled studies of approximately 100 to 300 volunteer patients (people with the disease) assess the drug's effectiveness and takes about two years.

  10. Clinical Trial Phase III • This phase lasts approximately three years and usually involves 1,000 to 3,000 patients in clinics and hospitals. Physicians monitor patients closely to determine efficacy and identify adverse reactions.

  11. Approval • Once the FDA approves the NDA, the new medicine becomes available for physicians to prescribe. • The company must continue to submit periodic reports to the FDA, including any cases of adverse reactions and appropriate quality-control records. • For some medicines, the FDA requires additional studies (Phase IV) to evaluate long-term effects.

  12. Clinical Trials Preclinical Phase I Phase II Phase III FDA Phase IV Testing Years Test Population Purpose Success Rate 3.5 1 2 3 2.5 Lab and 20-80 healthy 100-300 patient 1000-3000 animal studies volunteers volunteers patient volunteers Assess safety Determine Evaluate Verify effectiveness Review Additional and biological safety and effectiveness, monitor adverse process / post marketing activity dosage look for side reactions from Approval testing required effects long term use by FDA 5000 1 .compds Only 5 enter trials approved evaluated File IND at FDA File NDA at FDA

  13. Cardiovascular

  14. Cardiovascular • Ticagrelor (Brilinta®) • Astra Zeneca • Pre-registration: Launch 2010 • Dabigatran (Pradaxa®) • Boehringer Ingelheim • Phase III • Rivaroxaban (Xarelto®) • Bayer/Johnson & Johnson • Phase III: Launch 2010 • Fewer heart attacks and lower death rate than Plavix arm in 18,000 patients • Rapid onset, reversible anti-platelet • Does not require hepatic activation • Twice daily oral dosage Direct Thrombin Inhibitor • Rapid onset, lower risk of bleeding vs. warfarin • Once daily, no monitoring Factor Xa Inhibitor • Currently approved for prevention of post surgical VTE in Canada and Britain Once daily, no monitoring

  15. Biotransformation and Mode of Action of Clopidogrel, Prasugrel, and TicagrelorN Engl J Med 361:1108, September 10, 2009 Editorial

  16. Cardiovascular • Ticagrelor (Brilinta®) • Astra Zeneca • Pre-registration: Launch 2010 • Dabigatran (Pradaxa®) • Boehringer Ingelheim • Phase III • Rivaroxaban (Xarelto®) • Bayer/Johnson & Johnson • Phase III: Launch 2010 • Fewer heart attacks and lower death rate than Plavix arm in 18,000 patients • Rapid onset, reversible anti-platelet • Does not require hepatic activation • Twice daily oral dosage Direct Thrombin Inhibitor • Rapid onset, lower risk of bleeding vs. warfarin • Once daily, no monitoring Factor Xa Inhibitor • Currently approved for prevention of post surgical VTE in Canada and Britain Once daily, no monitoring

  17. Cardiovascular • PHASE III Factor Xa Inhibitors • Apixaban • Pfizer/Bristol Myers Squibb • Edoxaban • Daiichi Sankyo • PHASE II • Betrixaban • Merck/Portola • Elingrel • Novarits/Portola • Single doses cause fewer adverse bleeding events Factor Xa Inhibitor Adenosine Diphosphate Receptor Antagonist

  18. Cardiovascular • Rosuvastatin/Fenobiric Acid (Certriad®) • Astra Zeneca/Abbott • Darapladib • GlaxoSmithKline • SCH-530348 • Shering Plough Lipoprotein Associated Phospholipase A2 Inhibitor (lp-PLA2) Thrombin Receptor (PAR-1) antagonist

  19. Pulmonary Arterial Hypertension • Treprostinil • United Therapeutics • Phase III • Sitaxsentan (Thelin®) • Pfizer • Phase III • Oral form of injectable Remodulin® • Sustained Release Endothelin-A Antagonist

  20. Multiple Sclerosis

  21. Multiple Sclerosis • Pegylated Interferon beta 1-a (Avonex®) • Biogen Idec • Phase III: Launch 2011 • Cladribine • EMD Serono/Merck • Pre-registration • Longer lasting drug to be self administered subcutaneously every other week • New formulation of anti-leukemia injectable Leustatin® • Reduced relapse rates • Short treatment course of 8-20 days per year

  22. Multiple Sclerosis • Dalfampridine-ER (Ampyra®) • Acorda/Elan • Released January 2010 • FTY-720 (Fingolimod) • Novartis/Mitubishi Tanabe • Phase III • FDA panel supports June 2010 • Adjunct treatment to improve walking speed (not a disease modifying agent) Sphingosine 1-Phosphate Receptor Modulator • Makes T cells unresponsive to stimuli leading to destruction of myelin

  23. Alzheimer’s Disease

  24. Alzheimer’s Disease • Bapineuzumab • Wyeth/Elan • Phase III • Solanezumab • Lilly • Dimebon • Pfizer • LY450139 • Lilly Beta-Amyloid Antibody • Binds to and removes accumulation of beta-amyloid in the brain • Binds soluble beta-amyloid outside of the brain • Lower risk for toxic events • Inhibits cell death, stimulates neurite growth • Old OTC Russian antihistamine Gamma Secretase Inhibitor • Inhibits beta-amyloid producing enzyme

  25. Chemotherapy

  26. Monoclonal Antibodies

  27. Oncology • Denosumab (Prolia®) • Amgen • On market June 2010 • Sipuleucel-T (Provenge®) • Dendreon/Kirin • Pre-registration: Launch 2010 • Ipilimumab • Medarex/BMS • Phase III: Launch 2010 Anti-Osteoporosis Monoclonal Antibody • Treat bone metastases related to cancer Prostate Cancer Vaccine Blocks effects of negative T-cell regulator CTLA-4 • Targets malignant melanoma, lung cancer, lymphoma, and prostate cancer

  28. Oncology • Abiraterone • Cougar Biotechnology/J&J • Phase II/III: Launch 2012 • Enzastaurin • Eli Lilly • Phase III: Launch 2014 • PHASE II • Tremelimumab - Medarex/Pfizer • BSI-201 - BiPar/Sanofi-Aventis • Anti-tumor effect in refractory or resistant prostate cancer • Inhibits an enzyme necessary for testosterone production anywhere in the body Phosphatidylinositol 3-Kinase (PI3K) Inhibitor • Results in apoptotic cell death • Testing in non-Hodgkin’s lymphoma • Testing in prostate and bladder cancers Poly(ADPribiose) inhibitor • Testing in triple-negative breast cancer

  29. Pain Pathways

  30. Pain Management Deter Diversion • Oxycodone SR (Remoxy®) • King/Pain Therapeutics • Phase III • Oxycodone-IR/Niacin (Acurox®) • King/Acura • Phase III • Hydromorphone ER (Exalgo®) • CominatoRx/Coridien/Neuromed • Phase III • ORADUR-based • High viscosity base, when crushed with water forms thick gel (cannot inject or snort) • Niacin induced side effects when taken too often • OROS osmotic pill pump for controlled release

  31. Pain Management • Duloxetine (Cymbalta®) • Lilly • Phase III • Nitraproxen (Naproxcinod®) • NicOx • Phase III • Naproxen-EC/Esomeprazole-IR (Vimovo®) • AstraZeneca/POZEN • Phase III • Resubmitted for treatment of chronic pain indication • COX Inhibiting Nitric Oxide Donator • Relieve osteoarthritis with fewer GI and cardiovascular side effects • For patients at risk of NSAID related GI ulcers

  32. Anesthesia • Sugammedex (Bridion®) • Organon/Merck/Schering-Plough • Phase III Timely reversal of relaxant binding agents. Eight-nine times faster than neostigmine.

  33. Asthma/ COPD

  34. ONCE DAILY Asthma/COPD • Aclidinium/Formoterol • Forest/Almirall • Phase II • QVA149 (Indacaterol/Glycopyrrolate) • Novartis/Soesei • Phase II • QMF149 (Indacaterol/Mometasone) • Novartis • Phase II LAMA/LABA combo LABA/LAMA combo LABA/ICS combo LAMA: long acting muscarinic antagonist LABA: long acting beta antagonist ICS: inhaled corticosteroid

  35. Asthma/COPD • BI-1744-CL/Tiotropium • Boehringer-Ingelheim • Phase II • GW-642444/Fluticasone • GSK/Theravance • Phase III • Roflumilast (Daxas®) • Forest/Nycomed • Pre-registration: Launch 2010 in EU LABA/LAMA combo LABA/ICS combo Phosphodiesterase-4 (PDE-4) Inhibitor • GI side effects and weight loss • Oral dosage form

  36. Asthma/COPD • Mometasone/Formoterol (Dulera®) • Merck • Approved June 2010 • Indacaterol • Novartis • Phase III • Fluticasone/Salmeterol (Advair®) • GlaxoSmithKline • Phase III ICS/LABA combo BID dosing for asthma in ages 12+ Ultra-LABA monotherapy for COPD ICS/LABA combo Once daily dosing

  37. Weight Loss Management • Phentermine-CR/Topiramate (Qnexa®) • Vivus • Phase III: Launch in 2010 • Lorcaserin • Arena • Phase III • Bupropion-SR/Naltrexone-SR (Contrave®) • OrexigenTM Therapeutics • Phase III • Showed 10% weight loss in a large portion of patients and significantly reduced the HbA1C Selective Serotonin (5HT-2C) Agonist • No valvulopathy, depression or suicidal ideations

  38. Diabetes

  39. Diabetes • Dapagliflozin • BMS/AstraZeneca • Phase III: Launch in 2011 • Liraglutide (Victoza®) • Novo Nordisk • Launched January 2010 Sodium Glucose Transporter Protein (SGLT2) Inhibitor • Leads to increased excretion of glucose in the urine • Side effects of UTI and genital infection Glucagon-like Peptide-1 Analogue (GLP-1) • Daily subcutaneous injection • Approved in UK, Germany, Denmark, EU

  40. Diabetes • Teplizumab • Lilly/Macrogenics • Phase III • Inhaled Insulin (Afresa®) • MannKind • Phase III • Oral Insulin • Novo Nordisk • Phase II Anti-CD3 Monoclonal Antibody • Treatment of Type-1 Diabetes • Ultra rapid acting insulin for treatment of Type-1 and Type-2 Diabetes • First oral, pill form of insulin

  41. Rheumatoid Arthritis

  42. Rheumatoid Arthritis/Gout • CP690550 • Pfizer • Phase III: Launch in 2013 • Canakinumab (Ilaris®) • Novartis • Phase II/III Janus kinase-3 (JAK-3) Inhibitor • Inhibits passage of cytokines across cell membrane • Oral agent for rheumatoid arthritis • Currently indicated for cryopyrin associated periodic syndromes, testing in rheumatoid arthritis and gout

  43. Hepatitis C • PHASE III: Launch in 2012 • Telapravir • Vertex/J&J/Mitsubishi Tanabe • Boceprevir • Schering-Plough • PHASE II • R-7128 • Roche/Pharmasset • Filibuvir • Pfizer • Both attack the same HCV protease enzyme, but are based on different peptide chains With the decrease in the incidence of new cases of HCV in the US, firms may pull the plug if the market diminishes

  44. Anti-MRSA Anti-Infectives • Dalbavancin • Pfizer • Phase III • Ceftaroline fosamil • Takedea/Forest Labs • Phase III • Ceftobiprole • Phase III Glycopeptide • For MRSA related skin infections • Once-a-week IV dosing Cephalosporin • Kills gram positive bacteria like MRSA but also gram negative organisms • Pro-drug to increase its water solubility

  45. Conclusions • Very long, difficult process to bring a drug to market • No guarantees • No “blockbusters”

More Related