Movers and Shakers, Oct. - Dec. 2010 -- Pharma Matters Report


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Movers and Shakers, Oct. - Dec. 2010 -- Pharma Matters Report

  1. 1. Image CopyrIght: iSTOCKPHOTOMOVERS AND SHAKERSA PHARMA MATTERS REPORTA REVIEW OF OCTOBER – DECEMBER 2010. PUBLISHED FEBRUARY 2011. The Thomson Reuters quarterly report on the U.S. generics industry uses strategic intelligence and competitive analysis information from Newport Premium™, the critical product targeting and global business development system from the industry authority on the global generics market.
  2. 2. The Thomson Reuters quarterly report on the US generics industry using strategic intelligence and competitive analysis information from Newport Premium™, the critical product targeting and global business development system from the industry authority on the global generics market. In this quarterly report, we look at a few of the companies beginning to make their marks on the US generics market with their finished dose products or active ingredients, and analyze trends and statistics relating to the market as a whole. For more information on Thomson Reuters API Intelligence solutions, including Newport Premium, visit MATTERS | MOVERS AND SHAKERS
  3. 3. SECTIOn I: InTRODUCTIOn WHAT IS An AnDA?In 2010, the generics industry continued to thrive in the UnitedStates. Despite challenges, such as long approval timelines, An Abbreviated New Drug Applicationcompanies from 18 countries received a total of 412 final ANDA (ANDA) is the firstapprovals, down from 2009 when companies from 15 countries step for a genericreceived a total of 448 ANDA approvals. As in 2009, US-based drug in the U.S. Itcompanies received more approvals than any other country (159 is submitted to theapprovals going to 46 groups). Indian companies continued to FDA to prove that the generic versionmake inroads into the US generic market with 23 companies is bioequivalent toreceiving 132 approvals. the innovator drugIt is worth noting that at the end of 2010, the first Chinese in question. On approval, the genericcompany – Novast Laboratories – received a final ANDA version is addedapproval. An additional three Chinese companies have acquired to the Approvedfinal ANDAs from existing players in the US market and other Drug Products Listcompanies are awaiting approvals for their filings. Huahai of (“Orange Book”) andChina is already manufacturing benazepril for the US market. the company may manufacture andWe anticipate that, over time, manufacturing for a number market it. An ANDAof Chinese owned ANDAs will move to China and regulated may be submittedmarket players may move manufacturing to China to take before the patent onadvantage of lower costs. However, the backlog at the FDA will the innovator druglikely slow this transfer significantly. expires. However, in that case, theIn 2010, companies launched generic versions of several ANDA must include ablockbusters, among them sanofi’s anti-thrombotic Lovenox™ certification indicating that the filer does(enoxaparin sodium), Merck’s antihypertensive Cozaar™ (losartan not seek to marketpotassium), and Boehringer Ingelheim’s benign prostatic the product beforehyperplasia treatment Flomax™ (tamsulosin HCl). Additional the expiry of theblockbusters were exposed to Paragraph IV patent challenges, Orange Book-listedamong them Viread (tenofovir disoproxil fumarate), Gilead’s patents (“paragraph III certification”) orantiviral drug. During 2010, 33 molecules or combinations were that the filer believesfirst exposed to patent challenges, down from the previous year, that its productwhen more than 60 molecules or combinations received their first does not infringe theParagraph IV patent challenges. We believe that the decline in Orange Book-listedthe number of products first exposed to challenges is the result of patents or that the Orange Book-listeda diminishing number of products open to challenge and not an patents are invalidindication that generics companies are becoming less aggressive. (“paragraph IVOne of the key topics in the US generics market in 2010 was certification”).follow-on biologics. At long last, in 2010 the US market got WHAT ARE “A”the abbreviated pathway for approving biosimilar products. RATED DRUgS?However, it will be a while before we know how many “A” rated drugscompanies will use the new abbreviated pathway rather than are consideredcontinue to use the BLA route. therapeutically equivalent and can be substituted for each other. “A” rated drugs are designated as AA, AB, AN, AO, AP, and AT in the Orange Book. PHARMA MATTERS | MOVERS AND SHAKERS
  4. 4. Positioning for the follow-on biologics era was the driving force WHAT IS A U.S. DMF? behind several acquisitions and deals in 2010, such as Mylan’s acquisition of Bioniche Pharma. However, in 2010, M&A activity A DMF (Drug Master File) is a confidential wasn’t limited to biologics. The generics industry continued document to consolidate in pursuit of scale and diversification, both in covering a specific terms of geographic reach and product portfolios. Big Pharma manufacturing continued its interest in generics, both in established and facility, process, or emerging generics markets. Among others, Pfizer announced article used in the manufacturing, collaboration agreements with Strides Arcolab of India, sanofi- processing, aventis announced a joint venture (JV) with Japan’s Nichi-Iko, packaging, or storing GlaxoSmithKline expanded its business in Latin America by of a bulk drug. A DMF acquiring Laboratorios Phoenix in Argentina, Abbott acquired is reviewed by the Piramal’s Healthcare Solutions Business, and AstraZeneca FDA only if an ANDA or NDA referencing signed a deal for a portfolio of branded generic products to be that particular DMF supplied by India’s Torrent Pharmaceuticals. To subscribe to our is filed. An ANDA white papers covering deal making in the generics industry and or NDA will not be the US follow-on biologic market, click here. approved until any issues with the DMF That was a brief recap of happenings on the generics stage are resolved. in 2010. Now, let’s take a closer look at developments in the fourth quarter. SECTIOn II: AnDA APPROVALS TOTAL ‘A’-RATED AnDAS BY COUnTRY OF ORIgIn OF APPLICAnT FOR OCTOBER TO DECEMBER 2010 38 34 7 6 5 5 5 3 2 1 1 1 1 n nd s A a l d n na n le da y ae nd an di a pa ai n US i Ch rd i na la la Isr Ch Sp In rm rla Ja er Ice Jo Ca e Ge itz th Sw NePHARMA MATTERS | MOVERS AND SHAKERS
  5. 5. In the fourth quarter, 48 companies from 13 countries received WHAT IS Aa total of 109 approvals. US-based companies again received BIOSIMILARthe most final ANDA approvals, with 38 approvals going to ACCORDIng21 different corporate groups. The numbers were slightly TO U.S.down from the previous quarter, when 24 different US-based REgULATIOnS?companies received a total of 41 approvals. A biosimilar product is definedAs during the third quarter, Indian groups were in second place in the Act to meanduring the last quarter of 2010 with 34 approvals going to 15 a biological productgroups. Both the number of Indian groups with approvals and that is both “highlythe number of approvals were up from the third quarter when similar to the reference product29 final approvals went to nine Indian groups. notwithstandinggROUPS WITH THE MOST ‘A’-RATED AnDA APPROVALS minor differencesFOR OCTOBER TO DECEMBER 2010 in clinically inactive components” and 7 for which “there are no clinically 6 meaningful differences between 5 5 5 5 5 5 5 the biological product and the reference product in terms of the safety, 3 3 3 3 purity, and potency of the product.” Interchangeability is defined as a biological product that “may be substituted for the reference product without the intervention of the No W Ac Al Gl Te Hi Ap M Ap Bo Fr Al yla ners at es ke em km en va ta healthcare provider eh ot ax va so en m vis m n ex Ph rin rti a bi Pa n La ar iu La Ph cL sA who prescribed the In Gr ar ge Ph rt s A heim kP bo bo c ar m im ou rI G ar G ra ha ac m ra ng reference product.” ite p m to ac to eu rm Hf ac el d rie rie eu tic ac eu sI sL tic al eu tic nc al td In tic al KG s du sI al st nc sL rie td sL tdIn the fourth quarter of 2010, Novartis of Switzerland (parentof Sandoz) topped the list with seven final ANDA approvals,followed by Watson (US) with six approvals. A number ofcompanies received five ANDA approvals.In the third quarter, Novartis also received seven finalapprovals. However, during that quarter, seven was enough toearn only the third spot. During the third quarter of 2010, Mylan(US) was on top of the list with nine ANDA approvals, followedby Glenmark of India, with eight approvals. PHARMA MATTERS | MOVERS AND SHAKERS
  6. 6. WHAT IS A SECTIOn III: PARAgRAPH IV CHALLEngES PARAgRAPH IV CHALLEngE? In the fourth quarter of 2010, we learned of first Paragraph IV patent challenges on five new active ingredients or Bioequivalent combinations, down from eight during the previous quarter. generic versions of drugs that are not gROUPS WITH THE MOST PATEnT CHALLEngES On RECORD protected by patents AS OF DECEMBER 2010 can be produced and marketed in the 157 U.S. by any company, subject to FDA approval. However, a generic company may 95 obtain FDA approval 87 before patent expiry if 72 66 it certifies its product 51 44 does not infringe 40 36 35 31 30 the listed patents or the patents are invalid (paragraph IV certification). Patent p Hf td nc G nc td d d c c c holders may then sue In In In ou Lt Lt sA sL sL sI sI p es s ex Gr n Co ou rie ie al rti rie rie pi ni ot or the ANDA filer for tic Gr va ys Lu to yo st st pa Ap at eu No ra du du dd nk vis m or bo ac Sa In In Re Co ta ab patent infringement. If m La Ac al al hi xL Dr al ar tic tic n iic tic Ph pa yla eu eu the patent holder sues Da eu Im n M ac ac ac so m m m at the ANDA filer within ar ar ar W Ph Ph Ph va n 45 days of notification, r Su Pa Te the FDA may not approve the ANDA for 30 months from the date of notification. If Teva continues to be associated with more patent challenges no suit is filed within than any other company. At the time of this writing, we 45 days, the FDA may continued to link the company to challenges on 157 products. approve the ANDA at Mylan, with associations to 95 products with patent challenges, any time. stayed in the second spot and increased the lead over Novartis, with whom we associated 87 challenged products. 160, pat nPHARMA MATTERS | MOVERS AND SHAKERS
  7. 7. PRODUCTS FIRST ExPOSED TO PARAgRAPH IV CHALLEngES, AS REPORTEDBY THE FDA BETWEEn OCTOBER AnD DECEMBER 2010ACTIVE IngREDIEnT: • Lupin and Mylan have submitted ANDAs with Paragraphdarunavir ethanolate IV certification for generic versions of Prezista (darunavirPOSTED BY FDA: ethanolate) tablets.04 October 2010 • The Orange Book lists several patents covering Prezista tablets,BRAnD nAME: expiring between August 25, 2012 and December 26, 2026.Prezista® Tibotec’s suit against Lupin and Mylan alleges infringementnDA HOLDER: of US Patent 7,700,645, which claims a novel ethanolate formTibotec of darunavir useful for the treatment of HIV infections. That patent will expire on December 26, 2026. In another suit against Lupin and Mylan, The United States of America and the University of Illinois have alleged infringement of US Patent 7,470,506. That patent is directed to the treatment of HIV infection in adults and pediatric patients over the age of 6 years and will expire on June 23, 2019. Tibotec holds a non-exclusive license to US Patent 7,470,506 through an agreement with the University of Illinois. • At the time the first ANDA with Paragraph IV certification was submitted for a generic version of Prezista tablets, Cipla, Hetero, and Matrix held DMFs for darunavir.ACTIVE IngREDIEnT: • Apotex has submitted an ANDA with Paragraph IV certificationdastinib for a generic version of Sprycel (dasatinib) tablets.POSTED BY FDA: • The Orange Book lists four patents covering Sprycel tablets.04 October 2010 US Patent 6,596,746 claims dasatinib specifically as well asBRAnD nAME: its uses for the treatment of cancer and a protein tyrosineSprycel® kinase-associated disorder. It will expire on June 28, 2020.nDA HOLDER:Bristol-Myers Squibb US Patent 7,125,875 concerns cyclic protein tyrosine kinase inhibitors and includes claims to their use in the treatment of chronic myelogenous leukemia. It will expire on April 13, 2020. US Patent 7,153,856 also concerns the use of cyclic protein tyrosine kinase inhibitors for the treatment of cancer. It will expire on April 28, 2020. US Patent 7,491,725 includes both drug substance and drug product claims directed to Sprycel and will expire on October 12, 2025. In its suit against Apotex, BMS has alleged infringement of all four patents. • At the time the first ANDA with Paragraph IV certification was submitted for a generic version of Sprycel tablets, Hubei Haosun held the only DMF for dasatinib reported by the FDA. PHARMA MATTERS | MOVERS AND SHAKERS
  8. 8. ACTIVE IngREDIEnT: • Actavis, Mylan, and Par are among the filers of ANDAs with doxepin HCl Paragraph IV certification for generic versions of Silenor POSTED BY FDA: (doxepin HCl) tablets. 18 October 2010 • The Orange Book lists eight patents covering the method of BRAnD nAME: use and formulation of Silenor tablets. Silenor® According to the Orange Book, the six patents directed to nDA HOLDER: the drug product will expire on January 9, 2015. Two patents Somaxon concerning the treatment of insomnia will expire on March 26, 2013 and February 17, 2020. Although the Actavis, Mylan, and Par ANDAs included Paragraph IV certification to seven of the eight patents, Somaxon has alleged infringement of only US Patent 6,211,229. That patent concerns the treatment of transient and short-term insomnia and will expire on February 17, 2020. • At the time the first ANDA with Paragraph IV certification was submitted for a generic version of Silenor tablets, Dipharma Francis, Sifavitor, and Teva held the only active DMFs for doxepin HCl reported by the FDA. ACTIVE IngREDIEnT: • Watson has submitted an ANDA with Paragraph IV hydromorphone HCl certification for a generic version of Exalgo (hydromorphone POSTED BY FDA: HCl) extended-release tablets. 18 november 2010 • The Orange Book lists two patents covering Exalgo extended- BRAnD nAME: release tablets. Exalgo® US Patent 5,702,725 and US Patent 5,914,131 include nDA HOLDER: claims directed to the Exalgo formulation and its use in the Mallinckrodt management of pain. Both patents will expire on July 7, 2014. Mallinckrodt’s suit against Watson alleges infringement of only US Patent 5,914,131. • Several companies hold active DMFs for hydromorphone HCl.PHARMA MATTERS | MOVERS AND SHAKERS
  9. 9. ACTIVE IngREDIEnT: • Roxane Laboratories has submitted an ANDA with Paragraphsodium oxybate IV certification for a generic version of Xyrem (sodiumPOSTED BY FDA: oxybate) oral solution.04 October 2010 • In a suit against Roxane, Jazz alleged infringement of all fiveBRAnD nAME: patents listed for Xyrem oral solution in the Orange Book atxyrem® the time the ANDA was submitted.nDA HOLDER: US Patent 6,780,889 and US Patent 7,262,219 include drugJazz Pharmaceuticals product claims directed to Xyrem oral solution and will expire on July 4, 2020. US Patent 7,668,730 concerns a method for distributing sodium oxybate under the control of a central pharmacy. It will expire on March 7, 2024. US Patent 7,765,106 and US Patent 7,765,107 concern methods of controlling the distribution of prescription drugs using a computer database. They will expire on June 16, 2024. In December 2010, Jazz announced that a newly issued patent related to Xyrem had been added to the Orange Book. US Patent 7,851,506 includes claims directed to the treatment of cataplexy in patients with narcolepsy. It will expire on December 22, 2019. Jazz later sued Roxane alleging infringement of that patent along with US Patent 6,472,431, which does not appear in the Orange Book listing for Xyrem. • Johnson Matthey submitted a DMF for sodium oxybate in August 2010. PHARMA MATTERS | MOVERS AND SHAKERS
  10. 10. SECTIOn IV: nOTABLE DEALS In the fourth quarter, both generics and innovators alike continued their expansion into emerging markets, including Latin America. Watson, for example, expanded its presence in Brazil by agreeing to pay $30 million for Moksha8, which supplies both original drugs and branded generics. Under the agreement, Moksha8 will market and distribute in Brazil and Mexico products manufactured by Watson. Pfizer, meanwhile, acquired a 40-percent stake in Brazil’s Laboratorio Teuto. At the same time, emerging market players made acquisitions in the United States. Hikma Pharmaceuticals (Jordan) has agreed to acquire Baxter’s injectables business and through it will gain a manufacturing facility and significant foothold in the US injectables market. Dr Reddy’s Laboratories of India, meanwhile, entered into a deal with GlaxoSmithKline to acquire the latter’s US penicillin business and a penicillin manufacturing facility in Bristol, Tennessee. According to Dr Reddy’s spokesperson, the company has aspirations to significantly increase its North American generics business. In the fourth quarter, we continued to see examples of companies expanding their presence in the value chain. Cambrex, a US-based API manufacturer and drug delivery company, paid $20 million in Q4 for a 51-percent stake in Zenara Pharma in India to gain access to Zenara’s formulation and finished dosage capabilities. And Aceto, a company that only a few years ago was primarily known as a distributor of APIs and chemicals, announced that it was paying $80M for Rising Pharmaceuticals, based in New Jersey. There continued to be considerable interest in niche products in the last quarter of 2010. For example, Zentiva, now part of sanofi-aventis, announced its acquisition of an inhaler franchise from Siegfried, allowing Zentiva to become a player in a market that is expected to develop rapidly after 2013 when a number of respiratory products will lose patent protection. Meanwhile, Teva acquired Théramex, a player focused on the gynaecological market, from Merck KGaA, and Amneal expanded into the dermatology market by taking control of Quinnova Pharmaceuticals. The latter markets a number of products for dermatitis and eczema treatments.PHARMA MATTERS | MOVERS AND SHAKERS
  11. 11. We also continued to see deal-making in the biologics arena.Actavis, which has aspirations to become a major player in thebiologics arena, is planning to acquire Bioton, based in Poland.Not to be outdone by generics, Big Pharma kept the pressureon with their own generics industry-focused deals involvingboth large and small molecules. In October, Pfizer signeda deal with Biocon under which Pfizer will have the right tocommercialize several recombinant insulins developed byBiocon. And right before New Year’s, Pfizer entered into anagreement with Akorn-Strides, a JV between US-based Akornand Indian Strides Arcolab, to purchase 16 approved and sixpending ANDAs from the joint venture.SECTIOn V: OPEnIng MOVESBased on our research of ANDA filings and Paragraph IVchallenges, we highlight some of the companies makingsignificant game plays in the US generics industry.ALKEM LABORATORIES, LTD.Alkem Laboratories, based in Mumbai, India, was foundedin 1974. The US FDA, UK MHRA, Brazil’s ANVISA, and otherauthorities approved the company’s dose manufacturingfacilities, and the company claims to export its products tomore than 40 countries.Alkem’s formulations have been in the US market since 2009.The company currently holds final approvals for three productsand a tentative approval for one, lamivudine. This tentatively-approved product was reviewed under expedited reviewprovisions for the President’s Emergency Plan for AIDS Relief(PEPFAR). The tentative approval made the product eligible forpurchase outside the United States even before US patent expiry.At around December 1, 2010, Alkem informed Shire that it hadfiled an ANDA with Paragraph IV certification for a genericversion of Fosrenol (lanthanum carbonate) chewable tablets.We believe that this is the first Paragraph IV filing by Alkem.Alkem is also acting as a contract manufacturer and is makingamlodipine besylate finished dose product for a number ofcompanies, including Breckenridge and Ascend. PHARMA MATTERS | MOVERS AND SHAKERS
  12. 12. STASOn PHARMACEUTICALS, InC. Stason Pharmaceuticals, based in Irvine, California, is a privately held pharmaceutical company involved in developing, manufacturing, and marketing both generic and branded products. Its primary area of development is oncology. The company was founded by Harry Fan and has a strategic alliance with Standard Chemical and Pharmaceutical Company of Taiwan, which was founded by his father and is today managed by his brother. While in the beginning the two companies worked separately, today Stason and Standard are closely collaborating and have a joint pipeline in the United States. Stason currently holds five ANDAs, but is geared to file four to five or more ANDAs per year, mostly in the areas of oncology and CNS. The two companies also have their eyes set on biopharmaceuticals. They jointly created Stonsa Biopharm, Inc., a new spin-off biopharmaceutical company, based in Southern California. In December 2010, Stason and Lonza announced that they had signed an agreement granting Stason a worldwide license to use Lonza’s GS (glutamine synthetase) Gene Expression System. Stason is also a player in the contract manufacturing arena and provides both non-high containment and high containment manufacturing services to a number of companies, including Par, Cypress, and Heritage. Stason is capable of manufacturing both solid and semi-solid dosage forms, including immediate and delayed-release tablets and capsules, fast-disintegrating tablets, creams, and lotions. HAnDA PHARMACEUTICALS, LLC. Handa Pharmaceuticals, based in Fremont, California, is a specialty pharmaceutical company founded by Dr. Fangyu “Bill” Liu in 2005. Liu previously served as Chief Operating Officer and Vice President of Product Development and Operations at Anchen Pharmaceuticals. Handa is focusing on difficult-to- formulate, controlled-release formulations. In July 2009, Fosun Pharmaceutical of China invested in Handa; today they own about 10 percent of the company. Handa and Fosun have announced that they will cooperate to jointly develop generic drugs and challenge patents both in the United States and in Europe. In July 2008, Handa announced that it had filed an ANDA for AstraZeneca’s Seroquel XR (quetiapine fumarate extended- release tablets). The company claimed that it was the first to file an ANDA with Paragraph IV certification for several strengths and should be entitled to 180 days of marketing exclusivity. In December 2010, Handa received tentative approval of its ANDA. According to the Chinese media, this was the first time that a company with Chinese ties has received a tentative approval for a patent challenge product and could be entitled to the 180-day generic exclusivity.PHARMA MATTERS | MOVERS AND SHAKERS
  13. 13. Image CopyrIght: REUTERS/Petr JosekBIologICsone of our new optIonal modules Follow-on biologics are fast becoming a reality in global pharmaceutical markets. The passing of the 2010 Healthcare Reform Act defines the framework and exclusivity rules concerning biosimilars in the US, and is expected to fuel increased activity in this important area for generics, traditional small-molecule focused innovators, and biotech companies. The Newport Biologics Module contains unique manufacturing process data covering biologic drugs. Companies considering pursuing biosimilar opportunities can analyze multiple potential bio-manufacturing processes for each drug, genetic sequences, process steps, starting materials, and equipment required, as well as review related patents and literature references. Also included is US BLA (Biologics License Application) data for drugs approved through this regulatory route. HOW TO SUBSCRIBE The Newport Biologics Module is an optional subscription module that may be added to your Newport Premium™ subscription for an additional annual charge. To get a quotation, contact your account manager or visit Also available to enhance your subscription are modules covering Generic Deals, Phase III Drugs and US Market Share.©2011 Thomson Reuters. All rights reserved. Thomson Reuters and theKinesis logo are trademarks of Thomson Reuters.
  14. 14. To sign up to our Pharma Matters range of publications visit: THE ONES TO WATCH Focuses on the latest phase changes in the pharmaceutical pipeline. MOVERS AND SHAKERS Unravels the most significant game-play in the U.S. generics market. THE CUTTING EDGE OF CHEMISTRY Insights into the chemistry advances transforming drug discovery and development. ABOUT NEWPORT PREMIUM Newport Premium is the critical product targeting and global business development system from Thomson Reuters, the industry authority on the global generics market. Created specifically for generic pharmaceutical companies and strategic API manufacturers, it can help you to identify and evaluate product opportunities worldwide, ensuring you’ll be first to find the generic product and niche opportunity, first to make the deal, and first to get to market. ABOUT THOMSON REUTERS Thomson Reuters is the leading source of intelligent information for professionals around the world. Our customers are knowledge workers in key sectors of the global economy. We supply them with the intelligent information they need to succeed in fields that are vital to developed and emerging economies such as law, financial services, tax and accounting, healthcare, science, and media. Our knowledge and information is essential for drug companies to discover new drugs and get them to market faster, for researchers to find relevant papers and know what’s newly published in their subject, and for businesses to optimize their intellectual property and find competitive intelligence. NOTE TO PRESS: To request information or permission to reproduce content from this report, please contact: Paul Sandell Phone: + 44 (0)20 7433 4704 Email: For more information on Thomson Reuters API Intelligence solutions, including Newport Premium, please visit or email scientific.lifesciences@thomsonreuters.comhealthCare & sCIenCeregIonal offICesNorth AmericaPhiladelphia +1 800 336 4474 +1 215 386 0100Latin AmericaBrazil +55 11 8370 9845Other countries +1 215 823 5674Europe, Middle East and AfricaLondon +44 20 7433 4000Asia PacificSingapore +65 6775 5088Tokyo +81 3 5218 6500For a complete office list 1110 DACopyright © 2011 Thomson Reuters