Novel Drug Marketing Group 2 Mahinda C. Edirisooriya

Content Hepatocelluar Carcinoma (HCC) HCC distribution & Incidence Development of novel drug Novel drug company –Drug regulation and distribution –Investment, Annual estimation, Annual production, Distribution, Trend and Competition, Advertising, monitoring and feed back

Hepatocellular Carcinoma (HCC) Primary cancer Origin in the skin or in tissue that line or cover internal organ. HCC origin from Hepatocytes Secondary cancer Primary cancer metastasis to other organ or tissue and start cause cancer

Distribution of Hepatocellular carcinoma in the world Country New case/YDeath/Y USA15,00013,000 Europe53,60057,000 Rest of the 557,000530,000 world

Liver cancer incidence in Thailand Thailand New case 10,000 / year 1993 – 2003 Increased from9.0 to 19.8 / 100,000 Sa Kaeo province 1993 – 2003 Mortality From 3.1 to 26.1 / 100,000

Combination of risk factors for HCC Hepatitis B &C Aflatoxin & Alcohol Normal epithelial cell HCC Chronic hepatitis and/or cirrhosis Change hepatocytes Dysplastic hepatocytes History of pharmacology and Toxicology J. Essigmann

Development of novel drug Why “Modified Megestrol” Best? Megestrol Similar to female hormone progesterone Treating for breast cancer and endometrial cancer Inhibit gonadotropin production in pituitary result decrease estrogen secretion Inhibit cell growth “Modified megestrol” Consist of estrogen receptor binding ligand, Linker and Warhead Warhead bind to DNA and shield from DNA repair Transcriptional factor binding to ligand and disrupt transcription Leading to apoptosis

Life cycle of the drug Profit Risk Investment Patent lifetime Years after discovery History of pharmacology and Toxicology J. Essigmann

Drug regulation in Thailand Legal basis Drug license Manufacturing Sell (wholesale, retail) Importation Registration Assessment Quality control Product Distribution channel Quality monitoring Good Manufacturing practices (GMP) Drug promotion Advertising Inspection Control Pre-marketingPost-marketing

Novel drug company Target area – Thailand Investment Capital ProductMarket Premises Machinery Equipment Technology and knowledge Human resource Registration Clinical trials Safety monitoring Distribution Brand building Field forces Information Technology

Market Manufacturer Agent/distributor wholesalers Own distributor Governmental Pharmaceutical organization Health centers Private clinic Retail drugstores General and specialized hospital Consumers Distribution channel 60%30%8% 58%27%7%4% 6% 2%

Market cont. Annual production – Estimate Dosage160 mg/day At least 2 month of continuous treatment For one person= 160x30x2 mg/y/person = 9.6 g/Y/person For 10,000 new patients in Thailand= 9.6x10 4 g/y Estimate Annual Production of “Modified Megestrol” = 96 kg Annual Revenue – Estimation One dose (160 mg) wholesale = 4 $ For two month treatment (per person)= 240$ 1 kg “Modified Megestrol”= 4/160 x 10 6 $ Annual production 96kg worth = 4/160 x 10 6 x 96 $ = 25 x 10 3 $ Annual revenue Estimate= 25 x10 3 x 960 $ = 2.4 $ million In 2002 Total value of production and import amount of drug market in Thailand = US $ Our annual contribution for total drug market in Thailand= 0. 2 % Par pharmaceutical, INC, Spring Valley, NY Production and Revenue

Market cont… Trend and competition Association of South-east Asia Nation (ASEAN) agreed to create free trade area which will increase competition Tax barrier will be gone by 2010 Strong manufacture from other South Asian countries will enter to the Thai market Good post harvesting technology Vaccination for the Hepatitis B virus Government pharmaceutical organization

Market cont… Advertising – Approvals from the FDA – Publications through Media, booklets, posters Promotion – Awareness of novel drug – Access to educational, explanatory, and patient friendly materials

Market cont… Monitoring and feed back Hospital records Health care professionals Pharmacist Drugstores Patients Sales information

Summary Drug treat HCC High incidence of HCC in Southeast Asia due to dietary aflatoxin, hepatitis virus and cirrhosis SEA is the best market for most effective novel drug to treat HCC New Product successfully distribute to the market and sell under the provision of drug act. In Thailand

Conclusion Synthesis of “Modified Megestrol” Drug can produce DNA adduct that specific interact with the vER and selectively kill liver cancer cell Mechanism testing Mechanism testing - Test assumption that drug can form DNA adduct. The drug can form DNA adduct that bind to the vER Preclinical study To test the anti cancer drug properties in-vivo and in vitro Clinical trial We have done whereas have evidence that novel drug is good effective for the HCC Marketing New Product successfully distribute to the market and sell under the provision of drug act. In Thailand