HEALTHCARE SECTOR SECONDARY RESEARCH SAMPLE REPORT Market Landscape Assessment: Epidemiology, Current Treatments and Unmet Needs, Clinical and Preclinical Pipeline, Review of Key Trials, Emerging Profile of New Therapies Dan Meichenbaum 415.828.5265 [email protected] Will Anlyan 347.334.2562 [email protected] 1 Introduction of services Market Research Intelligence: Make More Informed Investment and Management Decisions Dectiva specializes in delivering quantitative and qualitative market research data and analysis to leading investment and business decision makers. By providing access to a a global panel of survey and interview respondents, Dectiva empowers its clients with proprietary knowledge and timely insights in the life sciences industry. Dectiva serves institutional investment, venture capital, private equity, and corporate entities. Clients Use Dectiva's Primary Market Research Platform To: » » » » » » Survey targeted physician and patient groups to forecast demand and rate of adoption for new products Test new target product profiles to investigate strengths, weaknesses, opportunities, and positioning relative to the competitive set Identify unmet therapeutic needs and determine potential barriers to new product adoption Analyze existing target markets to understand usage rates of competing products where sales information is incomplete Collect early feedback from physicians, payers, and patients to inform new product design and development of target product profiles Evaluate key drivers of market share to guide product enhancements and post-marketing efforts Clients Use Dectiva's Secondary Market Research Services To Better Understand: » » » » » » Disease definition and epidemiology Current treatments, market size by number of patients and sales volume, and unmet therapeutic needs Clinical and preclinical pipelines Status and results of key trials Emerging profiles of competing new therapies Pricing, coverage, and reimbursement issues Clinical Trial Recruitment - Investigators and Patients: Leveraging our global network, Dectiva performs custom recruitment campaigns of clinical investigators and patients for enrollment in clinical trials. 2 Secondary Research Detailed Overview Secondary Research Market Landscape Assessment Extensive literature review: » Scientific publications » Trade journal and databases » Securities analyst reports » Government sponsored databases » Syndicated databases (based on client access) Ideal for companies/investors exploring: »New products in new areas »New applications for existing products Information distilled to deliver insights, as well as data Collect and analyze technical data on: »Disease classification info »Diagnostic algorithm »Epidemiology »Market drivers »Competitive intelligence (detailed pipeline and existing market overviews) Completed within 5-7 days Structured and customized reports to support business planning and investment decisions Completed within 3-5 days 3 Case Study - Overview SECTOR Life Sciences – Thrombocytopenia OBJECTIVES Opportunity assessment » Market size, growth » Current treatments » Unmet needs Competitive landscape analysis » Current treatments, advantages, limitations » Pipeline competitors, trial design and potential positioning Client Background Pharmaceutical client evaluating multiple opportunities for in-licensing Needed preliminary assessment of market attractiveness based on secondary data to prioritize different opportunities Next steps would be to conduct primary research to validate findings and to quantify value of specific asset opportunity Disease Area Thrombocytopenia Diverse patient population Minimal syndicated market data available 4 Case Study - Table of Contents Disease Definition and Epidemiology Current Treatments and Unmet Needs Clinical and Preclinical Pipeline Key Trials Conclusions Emerging Profile of New Therapies 5 Disease Definition: Diverse Causes • Thrombocytopenia is a reduction in platelets (<100,000 platelets/µL), which can lead to excessive bleeding. The condition is caused by: – Suppression of megakaryocytes (responsible for platelet production) in the bone marrow. – Immune disorders that produce antibodies that destroy platelets. – Medications that result in myelosuppression and/or immunological destruction of platelets. THROMBOCYTOPENIA CAUSES Platelet Production • Bone marrow diseases (leukemia, lymphoma, MDS, multiple myeloma) • Myelosuppressive therapies (e.g., chemotherapy, radiation) • Reduced thrombopoietin in the liver due to liver disease (chronic hepatitis C, cirrhosis, liver failure) • Systemic viral or bacterial infection – HIV, HCV, HCB – Dengue fever infects megakaryocytes • Sepsis • Vitamin B12 or folic acid deficiency • Numerous hereditary syndromes Platelet Destruction • Immune or idiopathic thrombocytopenic purpura (ITP) • Autoimmune disorders (e.g., lupus, rheumatoid arthritis) • Disseminated intravascular coagulopathy (DIC) associated with cancer, sepsis or infection • Medications: drug-antibody complexes bind and activate platelets – Heparin-induced thrombocytopenia is a rare, but serious example of this 6 Epidemiology: 200,000+ US Cases Per Year • • • Medication induced thrombocytopenia has increased with introduction of new therapies that cause hematological complications (e.g., antiinflammatories, cardiac & ulcer drugs, antibiotics). Reduced thrombopoietin production in the liver results in thrombocytopenia in patients with chronic HCV infection and liver disease. Other forms of thrombocytopenia are more rare; congenital thrombocytopenia, though quite varied, accounts for <X% of all cases. US INCIDENCE OF THROMBOCYTOPENIA Cause Comments Est. US 2008 Incidence Annual Growth ITP1 • Scientific references cite incidence of X/100,000 in adults and X/1MM in children • Non-scientific references cite X/1MM. XXXXX But may be as high as XXXXX +X% Chemotherapy induced thrombocytopenia2 • Based on Decision Resources estimates and projections XXXXX +X% Heparin induced thrombocytopenia (HIT)3 • XX% of patients treated with unfractionated heparin • XX% develop HIT with thrombosis • Estimates based only on cardiovascular patients XXXXX +X% Myelodysplatic syndromes (MDS)4 • MDS est 2008 incidence = XXXXX • Thrombocytopenia occurs in ~XX% of patients XXXXX +X% Chronic hepatitis C infection5 • XX M Americans chronically infected • XX% of chronic HCV patients affected XXXXX +X% HIV/AIDS6 • XXXXX diagnosed cases of AIDS in US in 200X • 1 yr incidence is XX% in patients with AIDS XXXXX +X% Source: 1. ITP: Frederiksen H, Schmidt K, 1999; 2. Decision Resources, 2007; 3. HIT: Ohman EM, et al, 2005; 4. MDS: Ma X, et al, 2007 (est. 2003 MDS incidence rate of 3.56/100,000 applied to 2008 US population); Hagop K, et al, 2007; 5. HCV: Armstrong GL, et al, 2006; ChongShan W, et al, 2004; 6. HIV: CDC, HIV/AIDS Surveillance Report, 2005; Moore R, www.hopkins-hivguide.org 7 Current Treatment Approach: Disrupt antibody-mediated destruction • • • ITP treatment guidelines established by American Society of Hematology (ASH) in 1996 are still in place today. Following acute situations, many patients experience spontaneous remission. Patients whose symptoms persist require further treatment; ~X% of patients become refractory. ITP TREATMENT APPROACH 1st Line Platelets >30,000/µL, asymptomatic or minor purpura Dx Platelets 20,00030,000/µL and/or significant mucous membrane bleeding 2nd Line / 3rd Line Observation Consider Splenectomy Platelets <30,000/µL after 4-6 weeks of treatment Cylcophosphamide / Chemo Comb. Drug Tx Glucocorticoids Rituximab Off-Label Other Experimental Tx Platelets <20,000/µL and/or significant mucous membrane bleeding Hospitalization & Drug Tx High dose IV glucocorticoids, IVIG, platelet transfusions Source: George JN, et al, “ITP: A Practice Guideline Developed by Explicit Methods for the American Society of Hematology,” Blood, 1996 8 Current Treatment Approaches: Treat Underlying Cause • In other forms of thrombocytopenia, physicians must assess underlying disease or risk-benefit of treatments causing reduced platelet levels. TREATMENT APPROACH FOR OTHER FORMS OF THROMBOCYTOPENIA Chemotherapy Induced Thrombocytopenia Platelet transfusion Neumega (oprelvekin, IL-11) Heparin Induced Thrombocytopenia Direct Thrombin Inhibitors (argatroban, lepirudin) Chronic Hepatitis C / Cirrhosis Interferon Therapy Liver Transplant HIV Antiretroviral Therapy (AZT, ART) 9 Current Treatments: Most Drugs are Immunomodulators Prednisone IV Gamma Globulin (IVIG) Rho(D) Immune Glubulin (Anti-D) Splenectomy Neumega (Oprelvekin) Rituximab MOA / Rationale • Prevents bleeding • Raises platelet count quickly • Interrupts antibody mediated platelet destruction • Approved for prevention of Rh immunization but also shown to interrupt platelet destruction • Spleen is site for antiplatelet antibody production and destruction of opsonized platelets • IL-11 enhances growth and maturation of IL-3 dependent megakaryocytic progenitors • Eliminate Blymphocytes needed for autoantibody production • May contribute to Fc receptor blockade Dosing / Admin • Begin 1mg/kg IV for 3 days; taper to <10-15 mg/d • 1g/kg/d IV for 2 d • 75µg/kg IM injection • Surgical procedure • 50µg/kg/d SC injection • 375mg/m2 four times at weekly intervals Duration of Therapy • 6 months • Can be intermittent for 18 months • Can be intermittent for 18 months • N/A • Given in 10 and 21 day courses • TBD Efficacy • Platelet recovery within 4 days vs 16 days in untreated • Platelet increase in 75% of pts within 3-4 weeks • 50% achieved normal levels • 68% response • Transiently increases platelet counts for 2-3 weeks • 75-85% of patients have initial response • 25-40% relapse within 5-10 years • 28-65% of patients did not require platelet transfusions, vs 7-41% in placebo arms • 40-46% CRs • 63% overall response • 2-48 months duration Safety • Adverse events associated with longterm steroid use (hyperglycemia, hypertension, weight gain, growth retardation) • 15-75% of patients have mild headache, backache, nausea, fever • Some risk of aseptic meningitis, alloimmune hemolysis • Risk of alloimmune hemolysis • Potential for renal failure • Risks of infection (lifelong use of antibiotics recommended by UK guidelines but not US) • Boxed warning for allergic reactions • Constitutional toxicities, peri-pheral edema • Low incidence of atrial arrhythmias and syncope • 22% mild/mod adverse events • 4% severe events Source: George JN, et al, 1996; Cines DB, et al, “Congenital and Acquired Thrombocytopenia, Hematology, 2004; Beardsley DS, “ITP in the 21st Century,” Hematology, 2006; Panzer S, “New Therapeutic Options for Adult Chronic ITP, Vox Sanguinis, 2008 10 Unmet Needs: Safer Treatments and Options for Refractory Cases • • Current treatment options present risks of significant side effects and efficacy typically achieve 70% response rates or less. Even splenectomy, considered a “cure” for ITP, has efficacy of up to XX% but XX% may relapse within 5-10 years. UNMET NEEDS Safer therapies for patients at risk of bleeding or overt bleeding tendency, to postpone splenectomy Drugs with more rapid onset of action Effective therapies for refractory patients Drugs for patients scheduled for minor or major surgery, who can not take steroids or IVIG Diagnostics to more quickly and effectively identify patients with ITP versus other conditions Source: Panzer S, 2008; Decision Resources, “Managing the Side Effects of Chemotherapy,” 2007 11 Clinical Pipeline: Focus is on TPO receptor • • • • • • Even when the cause of thrombocytopenia is platelet destruction, patients may also be subject to decreased platelet production due to: – Antiplatelet antibodies binding to megakaryocytes – Apoptosis of megakaryocytes – Low thrombopoietin (TPO) levels 1st generation TPO growth factors were recombinant megakaryocyte growth factors. These agents tended to be immunogenic and were discontinued. 2nd generation agents are TPO peptide and non-peptide mimetics and TPO agonist antibodies. All bind to TPO receptor but in different ways. Potential concerns with new TPO agents are thrombosis, development of cancer/leukemia, antibody production, marrow fibrosis and rebound effects when treatment is stopped. Of the 11 clinical and 8 preclinical compounds in development for thrombocytopenia, at least 6 target the TPO receptor. Two compounds are awaiting FDA approval: – Nplate (Romiplostim/AMG 531) and Promacta (Eltrombopag) – Both will receive fast track or priority review, with launch expected by 20XX 12 Clinical Pipeline: Two Near-Term Entrants; Very Crowded Post-20XX Discontinued Discontinued Mechanism of Action TPO Receptor MOA2 MOA3 MOA4 13 Clinical Pipeline Source: Panzer S, 2008; ADIS R&D Insight; Amgen Press Release Jan 31, 2008 14 Clinical Pipeline Source: Panzer S, 2008; ADIS R&D Insight; GSK Press Release Dec 10, 2007 15 Clinical Pipeline • • Three additional TPO agonists are in clinical development – the XXX compounds are follow-up candidates to Promacta. Immunomodulators have also generated interest. CD20 antibodies affect the immune system’s ability to make autoantibodies. Drug Developer XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX XXXXX MOA Phase Indication ROA Thrombopoietin receptor agonist Thrombopoietin receptor agonist Syk tyrosine kinase inhibitor CD20 antigen antagonist CD20 antigen antagonist Platelet activating factor agonist CD16 antigen antagonist Anti-RhD immunoglobulin antagonist Thrombopoietin receptor agonist X ITP Oral X ITP Oral X ITP Oral X ITP IV X ITP IV X ITP IV X ITP IV X ITP IV X Thrombocytopenia Oral Source: ADIS R&D Insight; IDDB3 16 Preclinical Pipeline • Several companies have active research programs targeting thrombocytopenia, but very little data are available to assess activity. Drug Developer MOA Phase Indication ROA XXXXX XXXXX IL-1 agonists X Thrombocytopenia Injectable XXXXX XXXXX X TTP Injectable XXXXX XXXXX X XXXXX X Chemo-induced thrombocytopenia Thrombocytopenia Injectable XXXXX XXXXX XXXXX X Thrombocytopenia Injectable XXXXX XXXXX X ITP IV XXXXX XXXXX X ITP Injectable XXXXX XXXXX ADAM protein stimulants Thrombopoietin receptor agonist VPAC1 receptor antagonist LG543 growth factor agonist Anti-RhD immunoglobulin antagonist Staphylococcal protein A down regulates human B-lymphocyte and macrophage activation Platelet activating factor agonist X Thrombocytopenia IV IV Source: ADIS R&D Insight; IDDB3 17 Key Trials Overview • • • Most pipeline competitors have focused on ITP as their lead indication for registration. – GSK fielded two phase III studies (up to 200 subjects) and Amgen’s phase III had 210 subjects. – Most trials involve patients who are relapsed after at least one standard therapy or are refractory. Thrombocytopenia related to hepatitis C or chronic liver disease is another area of investment, where trial sizes are much larger (up to 750 patients). – HCV related studies aim to address thrombocytopenia such that patients can initiate and/or stay on antiviral therapy. Other thrombocytopenia studies in late phases address MDS and chemotherapy patients. 18 Key Trials: Promacta (Eltrombopag) in ITP Compound Cancer Sponsor Phase Patients Promacta ITP GSK III 200 Promacta ITP GSK III 189 Promacta ITP GSK II 99 Design Primary Endpoints EXTEND: Open-label, dose-adjustment, Safety and extension to evaluate safety and efficacy of tolerability, clinical eltrombopag for treatment of subjects with ITP lab tests, ocular previously enrolled in an eltrombopag trial. exams and Study allows individualized dose and schedule frequency of all for each subject. Ability to reduce the dose of AEs concomitant ITP medications in the presence of eltrombopag, while maintaining platelet counts = 50,000/microL will be investigated. RAISE: Randomized, double-blind, placebo- Pts w/ platelet counts between controlled study, to evaluate efficacy, safety 50,000/uL and and tolerability of eltrombopag, initially administered as 50 mg oral tablets once daily 400,000/uL during for six months in adult subjects with previously the 6 month treated chronic ITP. Subjects randomized 2:1, treatment period eltrombopag to placebo, and will be stratified based upon splenectomy status, use of ITP medication at baseline and baseline platelet count less than or equal to 15,000/µL. Randomized, double blind trial to assess Pts achieving efficacy, safety, tolerability in adults with platelet counts refractory, chronic ITP. Entry platelet counts =50,000/microL <30,000/microL for 6 mos who have failed at after 42 days of least one treatment; also included pts receiving treatment chronic maintenance steroids. Secondary Timing Endpoints Proportion of Start Jun 2006; patients achieving end Jul 2010 target platelet counts and duration of count elevation; signs and symptoms of ITP; QOL Duration of count Start Nov 2006; elevation; end Jul 2008 frequency of AEs; need for rescue treatment or ITP med; ITP symptoms; safety & tolerability Safety & tolerability; PK; PD; ITP symptoms, QOL Start Apr 2005; complete Source: ClinicalTrials.gov 19 Key Trials: Promacta (Eltrombopag) in HCV-related Thrombocytopenia Compound Cancer Sponsor Phase Patients Promacta HCV GSK III 750 Promacta HCV GSK III 500 Design Primary Secondary Timing Endpoints Endpoints Randomized, placebo controlled study in pts w/ SVR rate defined Pts with a shift in Start Oct 2007; chronic HCV to assess ability of eltrombopag to as percentage of platelet count from end Aug 2011 maintain a platelet count sufficient to facilitate subjects with non- <75,000/µL to initiation of antiviral therapy (Peg IFN alfadetectable HCV- >/=90,000/µL; 2a+ribavirin), to minimize antiviral therapy dose RNA at 24 weeks AEs, laboratory reductions and to avoid permanent post-completion of abnormalities, discontinuation of antiviral therapy. The clinical the planned ocular benefit of eltrombopag will be measured by the treatment period examinations, 12proportion of subjects who are able to achieve (i.e., Week 48 for lead ECGs a Sustained Virological Response (SVR). genotype 2/3 or Entry platelet count of <75,000/microL. Week 72 for nongenotype 2/3) Randomized, double blind trial to assess Need for platelet Bleeding; AEs, lab Start May 2008 platelet elevation to reduce need for platelet transfusion prior abnormalities, transfusions in chronic liver disease patients to, during and up ocular exams, with thrombocytopenia undergoing elective to seven days ECGmb invasive procedures; includes patients with following elective HCV, HBV, HIV, non-alcoholic steatohepatitis, invasive NASH. Patients with model of end stage liver procedures disease score (MELD) of 24 or less; entry platelet count <50,000/microL Source: ClinicalTrials.gov 20 Key Trials: Promacta (Eltrombopag) in HCV and Chemo-related Thrombocytopenia Compound Cancer Sponsor Phase Patients Promacta HCV GSK II 422 Promacta CIT GSK II 183 Design Primary Endpoints Randomized, double blind dose ranging study Pts shifting from (30, 50, 75 QD for 12 weeks) in chronic HCV baseline counts to related thrombocytopenia who are potential 100,000/microL candidates for antiviral therapy. after 4 weeks Secondary Endpoints Mean increase in platelet counts; safety & tolerability; population PK; PD; effect of antiviral outcome measures Randomized, double blind dose ranging study Change in Safety & to assess efficacy, safety, PK in patients baseline platelet tolerability; PD; receiving multiple cycles of chemo. Included count from 1st day platelet count pts with advanced solid tumors scheduled to of 2nd cycle to change; dose receive 1st line carboplatin/paclitaxel; subjects lowest count intensity of had no history of platelet or bleeding disorders. observed in the carbo/paclitaxel cycle Timing Start Feb 2005; complete Start Apr 2005; end Feb 2007 Source: ClinicalTrials.gov 21 Key Trials: Nplate (Romiplostim) in ITP Compound Cancer Sponsor Phase Patients Nplate ITP Nplate ITP Design Amgen II 100 Open label study in refractory ITP patients. Entry platelet count <=20,000/microL; failed at least 3 conventional treatments; on anticoagulant medication if pt has AF history. Amgen III 210 3b, randomized, SOC-controlled, open-label, 52-week treatment study to compare AMG 531 to medical SOC for ITP, with a 6-month Safety Follow-up. Non-splenectomized subjects who are 18 years or older, are diagnosed with ITP according to the American Society of Hematology (ASH) guidelines, and who have received at least 1 prior therapy for ITP will be eligible to screen for this study. Eligible subjects will be randomized to AMG 531 or medical SOC for ITP if their platelet count is < 50,000 or their platelet count falls to < 50,000 during or after a clinically-indicated taper or discontinuation of current ITP therapy. After the completion or discontinuation of the study treatment period, any subject who does not transfer in to another AMG 531 study will complete a 6-month Safety Follow-up period. Primary Secondary Endpoints Endpoints AEs; clinically Platelet response; significant transfusions changes in lab values and incidence of antibody formation Number of pts Time to undergoing splenectomy; splenectomy; platelet response; number of change in ITP treatment failures patient reported outcomes Timing Start Feb 2005; end Dec 2010 Start Nov 2006; end Jan 2010 Source: ClinicalTrials.gov 22 Key Trials: Nplate (Romiplostim) in MDS Compound Cancer Sponsor Phase Patients Nplate MDS Amgen II 240 Nplate MDS Amgen N/A 200 Design Primary Endpoints Randomized, double blind, placebo controlled Efficacy study evaluating efficacy and safety of treatment of thrombocytopenia in pts w/ low or intermediate-1 risk MDS. Starting dose of 750mcg up to 1000mcg or reduced to min of 250 mcg. Open label extension study to evaluate safety AEs of long term dosing in MDS. Patients with IPSS low or intermediate-1 risk MDS. Secondary Timing Endpoints Number of platelet Start May 2008; transfusions, end Jan 2011 bleeding events; platelet hematological improvement; overall survival; disease progression to AML; neutralizing antibodies versus drug; all AEs Platelet response; Start Jun 2007; transfusions; end Sep 2010 bleeding events Source: ClinicalTrials.gov 23 Key Trials: Nplate (Romiplostim) in MDSKey Trials: Other Phase II Compounds Compound Cancer Sponsor Phase Patients XXXXX ITP XXXXX II 106 XXXXX ITP XXXXX II 65 XXXXX ITP XXXXX II 24 XXXXX ITP XXXXX II 66 Design Primary Endpoints Open label, single arm study will evaluate the Overall response efficacy and safety of rituximab monotherapy in rate patients with refractory, relapsing or chronic idiopathic thrombocytopenic purpura (ITP). Patients will receive infusions of 1000mg i.v. on days 1 and 15. The anticipated time on study treatment is 3-12 months. Secondary Timing Endpoints Time to CR and Start May 2007; PR; duration of end Nov 2009 response and time to new therapy; AEs; hematological toxicity; infections; infusion reactions Double-blind, randomized, placebo-controlled, Platelet response PK; PK/PD dose-ranging, parallel-group study will assess relationship the efficacy, safety and tolerability. Once daily oral doses of 2.5, 5, 10, 20 mg or placebo for 28 days. Patients are refractory or relapsed after at least one prior therapy; entry platelet counts <50,000/mm3. Randomized, double blind placebo controlled Platelet counts Start Mar 2008; end May 2009 study in ITP with open label extension. Patients dosed 7.5 mg/day for 6 weeks. Includes patients with platelet counts <50,000/microL who have been treated with at least 1 ITP therapy. Phase I/II, non-randomized, open label dose Start Nov 2007 comparison study. Includes adults with chronic IPT that have failed at least one therapy. Entry platelet counts <30,000/microL and platelet levels <150,000/microL for >6 mos. Drug dosed twice, two weeks apart. Source: ClinicalTrials.gov 24 Conclusions Populations are small to moderate • • • • More than 200,000 patients in the US experience thrombocytopenia. Drug-induced thrombocytopenia (heparin, chemo or other drugs) are most common. Thrombocytopenia resulting from compromised liver function (chronic HCV infection and cirrhosis) is also a significant contributor to incidence. Estimates of ITP incidence span a large range (XXXX-XXXX/year), but condition is still considered rare. – – Small population allows for orphan designation and fast track or priority review Unmet need qualifies for fast tract or priority review Competition is poised to intensify • Treatment aims to address the underlying cause of thrombocytopenia (e.g., withdrawal of myelosuppressive therapy; antiviral therapy, liver transplant etc.). • In ITP, most treatments are immunomodulators targeting production or interaction of autoantibodies targeting platelets (e.g., IVIG, anti-D, rituximab). • New TPO mimetics are poised to enter the market in 20XX. – Amgen and GSK will specifically address thrombopoiesis with new oral and injectable therapies which have reported high (>75%) response rates in restoring platelets to safe levels. – Both will significantly change competitive landscape with investments in advertising, promotion and sales to create share of voice. 25 Conclusions Clinical pipeline is limited • • Only 11 compounds have entered the clinic and 8 appear to be in preclinical development. Several are focused on the TPO receptor, while others are immunomodulators or other MOAs. – TPO agents hold the most promise at this time, with Amgen and GSK in the lead. Clinical trials focus on ITP, but also HCV • Most competitors have focused on ITP as their lead indication for registration, due to potential for fast track or priority review. – Phase II and III studies require 100-200 patients • Companies have also fielded several studies in patients with chronic HCV infection and liver disease and Amgen has a large trial in MDS. – Phase III studies with HCV patients are larger (~500-750 patients) • Amgen, GSK and others are looking at chemotherapy induced thrombocytopenia, but investigation appears to be in phase II to date. • Based on additional safety studies being fielded, long-term use and safety are significant concerns. Specific studies are evaluating ocular effects. 26 Emerging Profile New agents must be effective, with relatively low toxicity Emerging Profile based on Clinical Pipeline MOA • Target TPO receptor or autoantibody activity Indication(s) • ITP (lead) • Thrombocytopenia related to chronic HCV or liver disease • Chemotherapy-induced thrombocytopenia (CIT) ROA and Dosing • Oral or subcutaneous dosing • QD Efficacy • 75-90% response, measured by achievement of platelet counts ≥50,000/µL • Duration of response ≥15 weeks • Reduced need for platelet infusions Safety • • • • Well tolerated; similar to placebo Mild headaches and fatigue Rare grade 3 or 4 toxicities (e.g., bleeding / thrombosis) Ocular effects TBD 27 Key References • • • • • • • • • • • • • Armstrong GL, et al, “Prevalence of Hepatitis C Virus Infection in the United States, 1999-2002,” Ann Intern Med, 2006 Beardsley DS, “ITP in the 21st Century,” Hematology, 2006 CDC, HIV/AIDS Surveillance Report, 2005 Chong-Shan W, et al, “Strong Association of Hepatitis C Virus Infection and Thrombocytopenia,” Clinical Infectious Diseases, 2004 Cines DB, et al, “Congenital and Acquired Thrombocytopenia, Hematology, 2004 Frederiksen H, Schmidt K, “Incidence of Idiopathic Thrombocytopenic Purpura in Adults Increases with Age,” Blood, 1999 Decision Resources, “Managing the Side Effects of Chemotherapy,” 2007 George JN, et al, “ITP: A Practice Guideline Developed by Explicit Methods for the American Society of Hematology,” Blood, 1996 Hagop K, et al, “Incidence and Impact of Thrombocytopenia in Myelodysplastic Syndromes,” Cancer, 2007 Ma X, et al, “Myelodysplastic Syndromes: Incidence and Survival in the US,” Cancer, 2007 Moore R, www.hopkins-hivguide.org Ohman EM, et al, “Identification, Diagnosis and Treatment of HIT and Thrombosis (CATCH Registry),” J Thromb Thrombolysis, 2005 Panzer S, “New Therapeutic Options for Adult Chronic ITP, Vox Sanguinis, 2008 28 Dan Meichenbaum 415.828.5265 [email protected] Will Anlyan 347.334.2562 [email protected] www.dectiva.com Follow us on Twitter! @Dectiva 29