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
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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
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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.
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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.
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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. challenge from a few products, namely, Sporanox
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India DRL & UCB over
Industry Watch Levetiracetam Patent Dispute r. Reddy’s Laboratories Ltd. (DRL) has filed an Abbreviated New Drug Application (ANDA) with D the US Food and Drug Administration (FDA) for its epilepsy drug product levetiracetam tablets (250mg, 500mg and 750mg concentrations) which prompted the Belgian pharmaceutical firm UCB to file a patent lawsuit against the Hyderabad-based drug company. Levetiracetam is the generic version of the drug product Keppra; while UCB is the patent holder of Keppera, and markets the drug in the US in 250mg, 500mg and 750mg concentrations as well, with annual sales recorded at US$234 million in US market. However, the Indian pharmaceutical company believed it was the first to file patent for the epilepsy drug and maintains that it has the first-to-file status along with one other unnamed filer on application for all dosage About Dr. Reddy’s Laboratories Ltd. strengths. On the other hand, UCB alleged that by filing an Since its inception in 1984, DRL has walked application under Para IV Certification on the two Orange the path of discovery and innovation in health sciences, with a mission to sustain and improve Book patents for the drug, DRL has committed patent the quality of life. Our competencies cover an infringements. Para IV Certification occurs when a generic entire pharmaceutical chain: basic research, manufacturer claims it is not infringing on a drug patent or finished dosages, generics, bulk actives, biotechnology and diagnostics. Their research that the patent is not valid. center uses cutting-edge technology and has discovered breakthrough pharmaceutical If DRL is successful in its litigation, it will benefit from solutions in therapeutic areas. In a short span, a 180-day marketing co-exclusivity pursuant to the July the company has filed for 64 patents, and 2003 FDA guidance on 180-day exclusivity when multiple became are the first Indian Company to out- license a molecule for clinical trials to Novo ANDAs are filed on the same day. Nordisk, the world leader in diabetes. In December last year, three studies have been conducted to show that levetiracetam, as an antiepileptic Contact Details: agent, appears to be effective in treating neuropathic pain, Dr. Reddy’s Laboratories Ltd. hence offering an alternative to traditional treatments and Address: 7-1-27 Ameerpet, Hyderabad analgesic drugs that are often unsuccessful. An advantage 500 016, India of using Levetiracetam is that it does not interact with other Tel: +91 40 2373 1946 drugs, causing a low incidence of adverse events and Fax: +91 40 2373 1955 improving patients’ sleep. Email: [email protected] A comprehensive study conducted by Dutch researchers also found levetiracetam to be more effective than other drug products such as lamotrigene, topiramate or gabapentin in the treatment of patients with strongly therapy-resistant epilepsy.
420 APBN ¥ Vol. 8 ¥ No. 8 ¥ 2004 Elder Pharma SECURES EXCLUSIVE Cosmoceuticals MARKETING AGREEMENT
Industry Watch
n collaboration with the French cosmetics and dermatological company Laboratories Biorga, Elder Pharma I will be entering an exclusive joint marketing campaign to promote some high-end skin care products in India. It marks the first time the Mimbai-based Elder Pharma, part of the Elder Group of pharmaceutical companies, has ventured into the market of cosmoceuticals, which combines the properties of cosmetics and pharmaceuticals. The products Laboratories Biorga plan to promote in the Indian market will be priced between US$8 and US$23, and had undergone clinical trials that differentiate it from the average skin creams. About 30 of Biorga’s skin-related products would be marketed in the joint venture. Laboratories Biorga is part of the Biorga Uriage Group and oversees a portfolio of about 80 products that are sold in over 35 countries worldwide, including Asian countries Japan, China, Taiwan and South Korea. Stephane Thevignot, Director of International Operations for Laboratories Biorga, believes that the Indian market is ready for niche dermatological products and About Elder Pharma their line would plug the gap between an over-the-counter (OTC) The Elder Group is one of the fastest growing skin product and a medicine prescribed by physicians. pharmaceutical companies in India and has enjoyed tremendous growth since its inception “We chose Elder as our partner in India owing to the similar in 1987. Elder has five manufacturing units which follow the most stringent quality control philosophy and size of the two companies. We feel that this is standards as per GMP guidelines while adapting the right time to enter India,” he said. The promotional campaign focused strategies to access the Indian would target dermatologists or skin specialists æ as the products marketplace by expanding into multiple markets and segments. Elder has established regional can only be sold through the prescription of a medical practitioner. offices in Delhi, Chennai, Calcutta and Mumbai. In India Elder is best known for owning the exclusive marketing rights for Tiger Balm, the popular topical analgesic. Contact Details: Biorga is its 25th international partner. Some of its other in- Elder Pharma licensing partners include Haw Par Healthcare (Singapore) for Address: Elder House, C-9, Dalia Industrial Tiger Balm, Blistex Inc. (USA) for Lip Care products, Zambon spa Estate, Off New Link Road, Andheri of Italy for Fluimicil, Covex (Spain) for Citicholine (Cerebro (W), Mumbai 400058, India Neuropsychiatry segment) and Ferrer (Spain) for Vimpocetine Tel: +91 22 2673 0058 (Cerebro Neuropsychiatry segment). Elder is also the owner of Fax: +91 22 2673 0051 Shelcal, a calcium supplement, which is its indigenous brand Email: [email protected] and also the largest turnover contributor. The products would address problems such as damaged, sensitive or pigmented skin, severely dry skin, anti-ageing, sunscreen, hair loss, dandruff treatment and acne – with all the manufacturing to be done in France.
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Lupin Pharma Collaborates with
Industry Watch Allergan to Promote Zymar™
upin Pharmaceuticals, Inc. announced its collaboration with Allergan to promote Zymar™ (gatifloxacin 0.3% ophthalmic solution) in US pediatric specialty Lmarket. The drug product is indicated for treatment of bacterial conjunctivitis caused by susceptible strains of bacteria. In March 2003, the US Food and Drug Administration (FDA) Zymar™ approved by the as the fourth generation ophthalmic fluoroquinolone to enter the market. Under the terms of the agreement, Lupin Pharmaceuticals will promote Zymar™ to high- volume pediatric prescribers. Zymar™ is already the top prescribed ophthalmic fluoroquinolone among eye-care professionals in the US. Vinita Gupta, President of Lupin Pharmaceuticals, said, “We are pleased to enter into this relationship with Allergan as we launch our presence in the US pediatric specialty segment. We believe that through this relationship, Lupin’s sales force will bring to the physician’s office two important products for complementary indications.” Lupin Pharmaceuticals is a subsidiary wholly owned by Lupin Limited. The company will be promoting Zymar™ via its pediatric specialty sales force. Earlier, Lupin’s pediatric sales force had launched its recently approved anti- infective product Suprax® on the market, licensed on an exclusive basis for the US to launch Cefixime Dry Suspension and Cefixime Tablet. Cefixime is a cephalosporin antibiotic used to treat ear infections of the ear, throat, urinary tract, respiratory tract (such as bronchitis). This newly established, 50-strong pediatric specialty sales force of Lupin Pharmaceuticals will target over 10,000 physicians with Suprax® the primary product in every presentation and the marketing effort will be complemented by additional promotional programs. A series of non-personal promotional campaigns, such as direct mailing and through product email, has been planned to reinforce the sales effort.
About Lupin Pharmaceuticals, Inc. Lupin Pharmaceuticals, Inc. is the wholly owned US subsidiary of Mumbai-based Lupin Limited, a leading Indian pharmaceutical company. Lupin Limited develops, manufactures and markets finished products, active pharmaceutical ingredients and intermediates. Lupin Limited is traded on all major exchanges in India, and nine of Lupin’s plants have been approved by the US FDA.
Contact Details: Lupin Limited Address: 159 CST Road, Kalina Santacruz (E), Mumbai 400098, India Tel: +91 22 5693 1011 Fax: +91 22 2654 0484 Email: [email protected]
422 APBN ¥ Vol. 8 ¥ No. 8 ¥ 2004 Japan Dainippon Pharma’s Latest Strategic 5-Year Management Plan
Industry Watch
n order to adapt to the changing management environment, Dainippon Pharmaceutical revised its previous Phase II 5-Year Management Plan I(FY2002-FY2006) that was previously released in May 2003, revolving around the “Realization of Qualitative Operations”. The revision was due to recent changes in the marketability of Dainippon’s forecasted core products Gatiflo (gatifloxacin), a synthetic anti-bacterial agent and rendered it necessary to revise the domestic and overseas revenue forecast. A Management Reform Committee and a Product Strategy Committee were formed to review the existing plan as well as to formulate a new strategy in an attempt to optimize Dainippon’s performance and to safeguard the corporate focus until fiscal year 2006. The teams revised earnings forecast and identified key operational objectives.
Item* Consolidated Operations Non-Consolidated Operations Original Plan Revised Plan Original Plan Revised Plan Net sales (¥100 million) 1,650 1,450 1,500 1,300 Operating income ratio (%) 17.0 11.0 18.0 11.5 Return on equity, ROE (%) 10.0 6.8 10.0 6.6 Earnings per share, EPS (¥) 96.0 55.0 95.0 53.0 Export sales ratio (%) 7.0 5.0 7.6 5.4 Number of employees 2,350 2,330 2,200 2,200
* The current joint venture agreement with Abbott Laboratories will terminate at the end of March 2006. Since there is currently no agreement beyond the fiscal year of 2006, Abbott products are not included in the sales figures above.
Key Operational Objectives There are five areas where changes had been made; these are • Strengthen domestic pharmaceutical operations; • Active investment in R&D; • Consolidate overseas operations; • Cost reduction measures; and • Implement new personnel system.
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1) Strengthen domestic pharmaceutical operations The company will aim to stretch its profit-earning potential by leveraging on its core products (e.g. gastrokinetic dug Gasmotin and vasodilator Prorenal). Meanwhile, Dainippon will selectively invest in new
Industry Watch products (e.g. anti-psychotic drug Lonasen and calcium channel blocker Zanidip) with plans for rapid development. 2) Active investment in R&D The focus will remain as the original plan, i.e. to invent new compound that satisfy market demand, and ensure that the new products are developed and made available to the market quickly. 3) Consolidate overseas operations Overseas operations will be actively sourcing for strategic out-licensing of the company’s products such as anti-dementia drug AC-3933, anti- anxiety/anti-depressant drug AC-5216 and aldose reductase inhibitor AS- 3201. 4) Cost reduction measures Dainippon will emphasize reducing fixed costs (e.g. reviewing the functions of departments providing support services), promote strong management of procurement, streamline operation and improve overall operating efficiency. 5) Implement new personnel system A performance orientated system will be implemented whereby employees’ remuneration shall be reviewed periodically. Personnel are encouraged to improve individual capability on a continuous basis. It is believed that this system will promote business competitiveness and personal motivation within the corporate workforce.
Contact Details: Dainippon Pharmaceutical Co. Ltd. Address: 6-8 Doshomachi 2-chome, Chuo-ku, Osaka 541-0045, Japan Tel: +81 6 6203 1407 Fax: +81 6 6203 5548 Email: [email protected] URL: www.dainippon-pharm.co.jp
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New Zealand
Industry Watch PVAC Therapy Development Discontinued
enesis Research and Development Corporation Ltd. (NZX/ASX: GEN) and Corixa had made decision to abort the development of PVACTM which G targets at psoriasis. The decision came after the completion of a randomized and placebo controlled clinical trial of PVAC in mild to moderate psoriasis patents. The results indicated that the treatment did not achieve 75% reduction in psoriasis area and severity index (PASI) score as compared to placebo treated patients. “The results of the randomized and placebo controlled trials do not justify further investment of resources in PVAC product development,” stated Dr. Jim Watson, CEO of Genesis.
About Psoriasis A common chronic, squamous dermatosis, marked by exacerbations and remissions and having a ploygenic inheritance pattern. The most distinctive histolofical findings in well- developed psoriasus are Munro microabscesses and spongiform pustules. It is characterized clinically by the presence of rounded, circumscribed, erythematous, dry scaling patches of vaious sizes, covered by greyish white or silvery white, umbilicated and lamellar scales, which have a predilection for the extensor surfaces, nails, scalp, genitalia and lumbosacral region. Central clearing and coalescence of the lesions produce a wide variety of clinical configurations, including annular or circinate, discoid or nummular, figurate and gyrate arrangements.
About Genesis Founded in 1994, Genesis is a New Zealand-based biotechnology company. It has built a broad genomic platform and has multiple product candidates in development both as health therapeutics and plant biotechnology products for agricultural markets. The Genesis therapeutics are targeted at immune disorders and cancer and are backed with an extensive patent portfolio. Genesis has a potential product in a Phase II Clinical Trial for the treatment of atopic dermatitis (eczema) with additional programs for cancer in clinical development. (Corporate URL: www.genesis.co.nz)
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