Disease State Primer: Ovarian Cancer

Transcription

1 Q Update Disease State Primer: Ovarian Cancer

2 Table of Contents I. Introduction Who is Lumleian and what is a disease state primer? What is our perspective on ovarian cancer? II. III. IV. Disease Overview and Care Paradigm What is ovarian cancer? Epidemiology by geography and risk factors Presentation, diagnosis, classification Current care paradigm and clinical evidence Emerging care paradigm Clinical Development Pipeline Clinical development pipeline mapping Traditional chemotherapies Anti-Angiogenesis agents Kinase Inhibitors Folate Receptor Targeting Agents Ovarian Cancer Vaccines Commercial Landscape Estimated use in ovarian cancer of branded therapies Global, US, EU, Japan market size and growth by brand Wall Street consensus forecasts for pipeline assets US growth decomposition: Rx volume, pricing, product mix US promotional spending, marketing mix and brand messaging V. Appendix Table of Acronyms More about Lumleian Slide Number

3 Executive Summary: Ovarian cancer refers to a malignant growth that arises in the ovaries, most often in the epithelial layer; this malignancy commonly goes undiagnosed until later stages, resulting in aggressive chemotherapeutic treatment and a high mortality rate. Disease Overview and Care Paradigm Clinical Development Pipeline Commercial Landscape Ovarian cancer is an aggressive gynecologic cancer with a high mortality rate, and an overall 5-year survival rate of 45%; ~15K patients die annually in the US from ovarian cancer Due to the lack of early-stage symptoms and a corresponding delay in diagnosis, ovarian cancer is the fifth most common cause of cancer death in women All ovarian cancer patients undergo the same surgical procedure, which involves the removal of the uterus, ovaries, and fallopian tubes Ovarian cancer is a highly chemo-sensitive cancer, and is typically treated aggressively in all stages, usually starting with an IV regimen of paclitaxel and carboplatin/cisplatin As of Q1 2012, Lumleian validated 81 assets in development for ovarian cancer The vast majority of the ovarian cancer pipeline is comprised of next-generation chemotherapeutic agents - DNA binders, microtubule destabilizers, and topoisomerase inhibitors are all validated classes of agents that dominate the ovarian cancer pipeline, owing to the chemo-sensitive nature of this tumor A number of novel, targeted drug classes are being pursued, including anti-angiogenesis agents, kinase inhibitors, tumor vaccines and immunotherapies - Numerous vascular-targeting agents are in development, including Roche s Trebananib, Sanofi s Aflibercept,Takeda s Ramucirumab, ImClone s Vargatef, and Exelixis XL999 - Despite early positive data supporting Roche s Avastin, disappointing Phase III survival data paired with significant side effects have drawn into question whether anti-vegf approaches will be a viable approach for ovarian cancer - Several clinical-stage programs are directed at intracellular kinases involved in cell signaling, proliferation, and cell cycle transcription factors, including Roche s Tarceva and AstraZeneca s Iressa; clinical trials are underway and it remains to be seen if these will provide a significant advantage over existing chemotherapy regimens Systemic chemotherapy dominates the treatment paradigm for both early- and late-stage ovarian cancer Lilly s Gemzar and Sanofi s Taxotere are the key branded drugs for the treatment of both early- and late-stage disease; additionally, BMS Taxol (paclitaxel) is still used despite the availability of generics Generic formulations of carboplatin, cisplatin, and doxorubicin are widely used in chemo regimens Source: Evaluate Pharma, BioPharm Insight, American Cancer Society: Cancer Facts and Figures Atlanta, Ga, American Cancer Society, 2011, S.A. Cannistra, R.C. Bast Jr., J.S. Berek et al. Progress in the management of gynecologic cancer: consensus summary statement. J Clin Oncol, 21 (Suppl. 10) (2003), pp

4 What is ovarian cancer? Description Etiology & Risk Factors Diagnosis & Symptom Progression Disease Burden Ovarian cancer is a malignant growth that arises in the ovaries, most often from epithelial tissue Most ovarian cancer patients are post-menopausal women Ovarian cancer is subdivided into epithelial cancers, germ cell tumors, and tumors of low malignant potential; the epithelial subtype is the most dominant (90% of cases) Women who have BRCA1/2 mutations or with hereditary non-polyposis colorectal cancer have the highest risk, but account for only 10% of patients Risk is inversely proportional to number of lifetime ovulations; pregnancies, lactation, oral contraceptives, tubal ligation and hysterectomy decrease risk Nulliparity, early menarche/ late menopause, hormone replacement therapy and endometriosis increase risk Screening tests, such as those which exist for the CA-125 and OVA-1 antigens, do not improve outcome Early symptoms are non-specific, resulting in late-stage diagnosis; tumors spread to the pelvis and upper abdomen, cause pelvic/abdominal pain, swelling; weight loss, pain, bowel or ureteral obstruction are symptoms of advanced disease Diagnosis: palpation of adnexal mass during pelvic examination, ultrasound, CA 125 & OVA-1 assessment, laparoscopy/laparotomy Estimated new cases: 21,990 (US, 2011) Estimated deaths: 15,460 (US, 2011) Lifetime incidence: 1 in 72 (1.39%); lifetime risk: 1 in 96 (1.04%) (US) Median age at diagnosis: 63 years. Age-adjusted incidence rate 12.9/100, Is ovarian cancer etiology well understood? Yes 2. Is ovarian cancer a primary cause of mortality? Yes No 3. Is ovarian cancer an acute or chronic disease? Acute Symptom Relief 7. Where is ovarian cancer treated? Out Patient Disease Treatment Inpatient Hospital Chronic 4. Is ovarian cancer a communicable disease? Yes 5. What is ovarian cancer s treatment goal? Disease Cure 6. Which specialties treat ovarian cancer? Gynecologist Gyn- Oncologist No No 8. Who pays for ovarian cancer (Rx)? Medical Oncologist Long Term Care 3 rd party Cash CMS 9. Does ovarian cancer impact a special population? Yes: Women No Sources: Kaku T et al. Histological classification of ovarian cancer. Med Electron Microsc. 36:1(2003), American Cancer Society: Cancer Facts and Figures 2011, Lutz AM et al. Early diagnosis of ovarian carcinoma: is a solution in sight? Radiology. 259:2 (2011), Jelovac D et al, Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J Clin. 61:3 (2011), SEER Cancer Statistics Review,

5 Global ovarian cancer incidence was 190K in 2010, with an estimated 22K new cases in the US; the incident patient population will grow at a rate consistent with the aging population. US Incidence 21,990 new diagnoses each year 15,460 deaths each year Lifetime risk 1.4 % Median age of diagnosis: 63 Age-adjusted incidence rate: 12.9 per 100,000 women 177, 578 women alive with a history of OC Global Incidence 190,000 new diagnoses each year 125,000 deaths each year Because 50% of ovarian cancer cases occur in women over the age of 65, the incident patient population will grow at a rate consistent with the aging population Risk Factors Post-menopausal women are more likely to develop OC Risk is inversely proportional to number of lifetime ovulations: pregnancies, lactation, oral contraceptives, tubal ligation and hysterectomy decrease risk; nulliparity, early menarche/late menopause and hormone replacement therapy increase risk Endometriosis (increased inflammation) increases the risk High-Risk Factors BRCA1 or BRCA2 mutations (increases lifetime risk from 1.4% in general population to 15-40% with a harmful mutation of BRCA 1/2) Hereditary non-polyposis colorectal cancer (increases lifetime risk from 1.4% to 10%) Sources: GloboCan 2008: World Cancer Report 2008, IARC 2010, PDQ Cancer Information Summary, NCI. Genetics of Breast and Ovarian Cancer

6 Telcyta and Eloxitine are two of the most advanced traditional chemotherapeutics attempting to provide improvements over existing standard of care, however, the currently available lowcost and well-know therapies present a significant hurdle to commercial success. 2 doxorubicin molecules bound to DNA Physiology Pathophysiology Hypothesized Mechanism Pipeline Unimpeded DNA synthesis and segregation is required for cell division Cancer cells divide at a faster rate than normal cells and fail to respond to normal mitosis inhibition signals Interference with DNA structure leads to inhibition of DNA and protein synthesis, stopping cell division and even causing cell death DNA binding is a well-established MOA for cancer treatment, and is the basis of many traditional chemotherapies Impeding other mechanisms of mitosis, such as disruption of microtubules or inhibition of topoisomerase are other mechanisms of traditional chemotherapy Phase III (6) Eloxatine (SNY) Telcyta (TELK) Paclical (Oasmia) Hycamtin (GSK) Karenitecin (BioNumerik) Opaxio (CTIC) Phase II (16) Irofulven Prolindao (ACCP) Zoptarelin Doxiorubicin (AEZS) Dacogen (ESALY) Alimta (LLY) EP-100 (Esperance) Iniparib (SNY) Olapanib (AZN) Rucaparib (CLVS) Tasisulam (LLY) BC-819 (BICL) Tirapazmine, Ispinesib (CYTK) Abraxane (CELG) Quinamed (ChemGenex) Vosaroxin (SNSS) Phase I (8) Picoplatin (PARD) GT-Mab 2.5 GEX (Glycotope) CBP-501 (CanBas) Belinostat (TPTGF) Lorvotuzumab (IMGN) SAR (IMGN) Brakiva (TLON), Pegylated Irinotecan (PFE) Sources: Bio-Pharma Insight; Clinical Trials.gov.

7 For the commercial analysis, we used the market share of each drug used in ovarian cancer patients, multiplied by that agent s total revenue numbers, to derive the commercial value of the ovarian cancer market. Oncology drug uses for Ovarian Cancer based on patients treated in 2011 US Paclitaxel Carboplatin 11.6% 12.4% Gemcitabine 7.4% Bevacizumab 7.5% Docetaxel 3.9% Topotecan Doxorubicin Liposomal Cisplatin Vinorelbine Paclitaxel Protei-bound 36.1% 33.9% 4.4% 3.4% 3.4% Other Cancer Ovarian Cancer Patient (Thousands) Noets: Revenues for each drug in ovarian cancer are calculated based on percentage of drug used in ovarian cancer as compared to other cancers. Sources: SDI (IMS) Oncology Tracker data

8 As the only chemotherapy drug with patent protection in ovarian treatment, Doxil s promotional spend dominated the market; the messaging emphasized the support by J&J for ovarian cancer patients Total Promotional Spend ($M) J F M A M J J A S O N D HCP Total Growth MR HCP $0.9M -51.7% DTC - - Share of voice HCP 55.8% % 100.0% 51.4% 95.9% 77.8% 100.0% % - - DTC HCP For your patients receiving or about to start treatment with Doxil for recurrent ovarian cancer or relapsed/refractory multiple myeloma, Doxil C.A.R.E.S. provides help and support. DOXIL HCP For your patients receiving or about to start treatment with Doxil for recurrent ovarian cancer or relapsed/refractory multiple myeloma... DOXIL Notes: Updated: 05/30/12 Sources: SDI Promotion Audits, Kantar Media Research