Industry Watch Industry Watch • Peplin’s Anti-AK Drug Enters IND Filing p.416 • China’s Anti-fungal Drug Marketp.418 • DRL & UCB over Levetiracetam Patent Dispute p.420 • Elder Pharma Secures Exclusive Cosmoceuticals Marketing Agreement p.421 • Lupin Pharma Collaborates with Allergan to Promote TM Zymar p.422 • Dainippon Pharma’s Latest Strategic 5-Year Management Plan p.423 •PVAC Therapy Development Discontinued p.426 APBN • Vol. 8 • No. 8 • 2004 415 www.asiabiotech.com Australia Industry Watch Peplin’s Anti-AK Drug n the latest development of its research collaboration with the Australian biotechnology I company Peplin Biotech Ltd, Allergan presented key information regarding the topical drug currently developed by Peplin for actinic keratosis (AK) and non- melanoma skin cancer (NMSC). Allergan will be filing an investigational new drug (IND) application with the US Food and Drug Administration (FDA) to initiate a Phase I/II proof of concept clinical trial in disease patients by the second quarter of 2004. As the sponsor of the IND, Allergan will likely be responsible for the product’s clinical development. Peplin has received an upfront payment of US$1 million on signing of its collaboration agreement with Allergan. Expected to receive up to another US$22 million, compromising of milestone payments and development payments, Peplin stands to receive royalty payments on net sales as well. Peplin has already received US$500, 000 as the first quarterly installment of the developmental payments for 2004. The projected IND filing will mark the next milestone under the collaboration agreement signed between the two companies, with further milestones on commencement of phase III clinical trials, NDA filing and NDA approval. About Peplin Biotech Contact Details: Peplin Biotech Based in Brisbane, Australia, Peplin Biotech Ltd. is a biotechnology company focused on the discovery and development of prescription human therapeutic Address: PO Box 346, Fortitude Valley products for the treatment of cancer. Its strategy is to leverage its pipeline of novel Queensland 4006, Australia proprietary products through collaborative development arrangements with Tel: +61 7 3854 0980 international pharmaceutical companies. Peplin’s lead product is a potential topical therapy for actinic keratosis and non-melanoma skin cancer æ the subject of a joint Fax: +61 7 3854 0980 development and license agreement with Allergan, Inc., a company based in Irvine, Email: [email protected] California. URL: www.peplin.com 416 APBN • Vol. 8 • No. 8 • 2004 Enters IND Filing Industry Watch Known as the early symptom of skin cancer, actinic keratosis is a common form of lesion of the outermost layer of the skin (epidermis) caused by long-term exposure to sunlight, particularly exposure to ultraviolet wavelengths. AKs are known to appear mostly in middle- aged patients (between 40 and 50) who have gone through years of chronic exposure to the sun. In regions where the sunlight is especially intense, AKs can be found in persons as young as in their teens or twenties. It is believed that AK affects at least half of the Caucasian population over 40 years of age and an alarming 78% of these patients suffer from multiple lesions. Up to a tenth of AKs would develop into squamous cell carcinoma (SCC) if left untreated. Squamous cell carcinoma is the second most common form of skin cancer after basal cell carcinoma. Occurring on all areas of the body but most common in areas exposed to the sun, squamous cell carcinoma is diagnosed by the appearance of tumors on parts of the body. The disease may also occur where the skin has been afflicted with certain kinds of injury: burns, scars, long- standing sores, exposure to X-rays or certain chemicals (such as arsenic and petroleum by-products). Several different conditions of AK have been identified by doctors as being precursors to the development of squamous cell carcinoma. About Allergan Contact Details: Allergan, Inc. With headquarters in Irvine, California, Allergan, Inc. is a global specialty pharmaceutical company that develops and commercializes Address: PO Box 19534, Irvine, innovative products for the eye care, neuromodulator, skin care and other California 92623, USA specialty markets. In addition to its discovery-to-development research Tel: +1 714 246 4500 programs, Allergan has global marketing and sales capabilities that deliver value to consumers, satisfy unmet medical needs and improve people’s lives. Fax: +1 714 246 4971 Driven by technology and innovation, Allergan addresses the needs of consumers across the world, with over 5,000 employees worldwide, four Research and Development facilities and three state-of-the-art manufacturing plants. APBN • Vol. 8 • No. 8 • 2004 417 www.asiabiotech.com China China’s Industry Watch Anti-fungal Drug Market Table 1. Hospital Consumption. Hospital Consumption Drug Market Share (%) Fluconazole 49.17 1 A survey conducted in 236 hospitals from 14 big cities had Itraconazole 13.49 revealed that hospital consumption amounted to US$1.55 billion Terbinafine 12.39 in 2002, with revenue standing at US$16.26 million. Econazole 6.94 Miconazole Nitrate 5.50 Fluconazole dominated the hospital consumption, capturing Bifonazole 3.09 Ketoconazole 3.09 49.17% of the market share, followed by Itraconazole at 13.49% Ciaclopirox Olamine 1.67 and Terbinafine at 12.39%. (Table 1) in terms of dosage, injection Clotrimazole/benzyl Alcohol 0.92 form is popular among hospitals, occupying 38.14% of the market, Amphotericin B 0.98 Selenium Sulfide 0.81 followed by capsule (24.94%), ointment (21.74%) and tablet Compound Ketoconazole 0.70 (13.20%) (Table 2). Mycospor 0.12 Flucytosine 0.41 By category, Triazole took up 62.97% of the market share while Amorolfine 0.21 Imidazole’s and antibiotics’ shares stood at 18.67% and 2.84%, Ofloxacin 0.05 respectively; the remaining 15.52% were filled by others. As of Clotrimazole 0.07 Miconazole 0.03 2002, Pfizer (Dalian) led the market, holding 32.79% market share, Compound Clotrimazole 0.04 followed by Janssen (Xi’an) at 27.24% and Shandong Qilu at 5.75% Methylrosaniline Chloride 0.02 (Table 3). Kitpat 0.01 Others 0.29 Among the 140 anti-fungal drug producers in China, the 10 Total 100 companies already covered >90% of the whole hospital market in the selected 14 cities. In particular, Diflucan (Pfizer), Daktarin (Jassen), Pevisone (Jassen), Triatop (Jassen), and Sporanox (Jassen) Table 2. Dosage Preference. had successfully occupied 50% of the market. Dosage Forms Market Share (%) Ranked as the No. 1 drug in hospitals, Diflucan by Dalian Injection 38.14 Pfizer accounted for 32.19% of the total hospital consumption, while Xi’an Jassen’s products: Sporanax, Pevisone, Daktarin and Capsule 24.94 Triatop ranked as No. 2, 3, 5 & 8 respectively. Lamisil (Beijing Ointment 21.74 Novartis) ranked No. 6. In a joint-venture orientated market, three Tablet 13.20 domestic products managed to squeeze in the top 10 list, these Injection Powder 1.13 drugs are: Dingke from Shandong Qilu, Sunve Pharmaceutical Co. Suspension 0.81 Ltd. and ciclopirox olamine from Beijing No. 3 Pharmaceutical Gel 0.01 Co. (Table 4). Suppository 0.02 Others 0.01 1 Beijing, Shanghai, Nanjing, Harbin, Tianjin, Guangzhou, Hangzhou, Shenyang, Jinan, Wuhan, Total 100 Changsha, Shijiazhuang, Xi’an, and Zhengzhou. 418 APBN • Vol. 8 • No. 8 • 2004 Industry Watch Table 3. Top 10 Companies by Market Share (2002). Table 4. Major Brands in 2002 Hospital Market. Rank Company Market Share (%) Brand Ingredient Dosage form Market Share (%) 1Dalian Pfizer 32.79 Diflucan Fluconazole Capsule 32.19 2 Xi’an Janssen 27.24 Sporanox Itraconazole Capsule 14.09 3 Shandong Qilu 5.75 Pevisone Econazole Ointment 5.07 4 Beijing Novartis 5.33 Dingke Terbinafine Ointment 5.55 5 Shanghai Sunve 3.24 Daktarin Miconazole Nitrate Ointment 5.41 6 Jiangsu Yangtze River 3.07 Lamisil Tablet Terbinafine Tablet 5.29 7 Shanghai Sine 2.37 Sunvecon Fluconazole Capsule 3.21 Triatop Ketoconazole Solution 2.50 8Hainan Mankexing 2.36 Mycospor Bifonazole Ointment 1.92 9Bayer 2.28 Ciclopirox Ciclopirox Olamine Ointment 1.58 10 Beijing No.6 (Wanhui Pharma) 1.66 Retail Market The reign looks quite different when the retail (from the same company), Lanmeishu cream from market for anti-fungal drug market is concerned. Tianjin SmithKline & French, Lamisil tablet from Xi’an Jassen dominated the markets in three big cities Novartis. æ Beijing, Shanghai and Guangzhou æ with Sporanox outperforms Daktarin in both Daktarin and Sporanax ranked No. 1 and No. 2; ingredient and effect aspects. Given sufficient time, while Pevisone and Triatop performing not bad at it is believed that Sporanox will gain more market all. This has very much to do with the products’ share, threatening Daktarin’s sovereignty. market positioning. Daktarin is targeted at dermatophytosis, Triatop at dandruff, Sporanox for On the other hand, competition between broad anti-fungal spectrum, and Pevisone at Lamisil (Lamisil tablet and Lanmeishu cream) and providing quick itch relief. Other products with Daktarin has been fierce over the OTC market. considerable coverage include Lamisil tablet from Strategies involving aggressive marketing effort Novartis, Lanmeishu cream from Tianjin SmithKline were launched in an attempt to create market & French. awareness. Some local Chinese companies (e.g. Shandong Lukang Pharmaceutical Group) were Daktarin remains the most popular choice quick to duplicate the ingredients and register among consumers living in these cities: Beijing, patent for Lamisil ahead of Novartis while the big Shanghai, Shenyang, Nanjing, Fuzhou, Dandong, players were fighting for more market share. The Huaiyin, Changzhou, Changshu and Haimen. In fact, aggressive launch has been successful and it has been the leading product in the anti-fungal indirectly helped the local companies to save the market for many years. However, its lead soon faces effort and costs in promoting their products.