Some countries did not report official data on pharmaceutical spending for either some indicators or years within the time span observed. These missing data refer to a total of 5 nations among free-market economies and 10 countries among former centrally planned economies. Most cases of partially or entirely missing data refer to the countries with relatively small population size in
TABLE1|PharmaceuticalexpenditureindicatorsaccordingtoWHOissuedHFA-DBdataforfree-marketeconomiesintheEuropeanRegionpriorto1989(5outof25countrieslackingsome relevantdatafromtheofficialrecords). FirstLastTotalTimeAnnualFirstLastTotalTimeAnnualFirstLastTotalTimeAnnual availableavailablechangespanincrementavailableavailablechangespanincrementavailableavailablechangespanincrement PE*as%PEas%PEas%(years)publicPEas%PublicPEas%publicPEas%(years)PEasPPP$PEasPPP$PEasPPP$(years) ofTHE**ofTHEofTHEofTPE***ofTPEofTPEpercapitapercapitapercapita AndorraN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A Austria9.6199011.72011+2.1210.1055.1199067.62011+12.5210.60$156.51990$533.12011+$376.621$17.93 Belgium28.1197015.52011−12.641−0.3158.5197064.32011+5.8410.14$41.91970$630.92011+$589.041$14.37 CyprusN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A DenmarkN/A6.82011N/AN/AN/A49.9198049.22011−0.731−0.02$53.81980$300.42011+$246.631$7.95 Finland12.6197013.22011+0.6410.0133.7197055.92011+22.2410.54$22.81970$446.22011+$423.441$10.33 France23.8197015.62011−8.241−0.2067.31970682011+0.7410.02$46.11970$641.12011+$595.041$14.51 Germany16.2197014.12011−2.141−0.0563.4197075.62011+12.2410.30$43.31970$632.62011+$589.341$14.37 Greece25.5197028.52011+3.0410.0760197073.72011+13.7410.33$40.81970$673.42011+$632.641$15.43 Iceland17.1197015.42011−1.741−0.0443.2197042.12011−1.141−0.03$29.91970$508.32011+$478.441$11.67 Ireland13.7197517.52011+3.8360.1143.41975782011+34.6360.96$37.31975$647.72011+$610.436$19.96 Israel15.5199514.72011−0.816−0.0539.3200643.72010+4.441.10N/AN/AN/AN/AN/A Italy21.8198815.72012−6.124−0.2561.5198845.52012−16.024−0.67$247.21988$482.22012+$235.024$9.79 Luxembourg19.719709.12008−10.638−0.2883.51970842008+0.5380.01$229.11995$4062008+$176.913$13.61 Malta23.69200127.982012+4.29110.3943.61200141.22012−2.4111−0.22N/AN/AN/AN/AN/A MonacoN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A Netherlands10.319729.42011−0.939−0.0260.1197278.42011+18.3390.47$32.31972$479.32011+$447.039$11.46 Norway7.819706.62012−1.242−0.0335.8197054.52012+18.7420.45$11.21970$390.42012+$379.242$9.03 Portugal13.4197017.92011+4.5410.1168.7197055.12011−13.641−0.33$6.31970$4692011+$462.741$11.29 SanMarinoN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A Spain21198017.42011−3.631−0.12641980712011+7.0310.23$761980$535.82011+$459.831$14.83 Sweden6.6197012.12011+5.5410.1362.9197058.32011−4.641−0.11$20.51970$4742011+$453.541$11.06 Switzerland11.319859.42011−1.926−0.0753.3199568.92011+15.6160.98$164.91985$530.72011+$365.826$14.07 Turkey10.7198126.62000+15.9190.84100198160.22000−39.8019−2.09$9.11981$120.72000+$111.619$5.87 United Kingdom14.7197011.42008−3.338−0.0959.4197084.72008+25.3380.67$23.41970$374.62008+$351.238$9.24 MEAN16.215.1−0.733.50.0157.562.95.432.30.16$68.0$488.2$420.234,1$12.30 STDEV6.26.26.310.10.2515.613.816.311.70.68$74.0$136.0$150.59,2$3.18 MIN6.66.6−12.611.0−0.3133.741.2−39.84.0−2.09$6.3$120.7$111.613$5.87 MAX28.128.515.942.00.84100.084.734.642.01.10$247.2$673.4$632.642$17.93 MEDIAN15.114.7−1.138.5−0.0459.464.35.838.00.23$40.8$482.2$447.039$11.67 *PE,Pharmaceuticalexpenditure. **THE,Totalhealthexpenditure. ***TPE,Totalpharmaceuticalexpenditure.
TABLE2|PharmaceuticalexpenditureindicatorsaccordingtoWHOissuedHFA-DBdataforformercentrally-plannedsocialisteconomiesintheEuropeanRegionpriorto1989(10outof28 countrieslackingsomerelevantdatafromtheofficialrecords). FirstLastTotalTimeAnnualFirstLastTotalTimeAnnualFirstLastTotalTimeAnnual availableavailablechangespanincrementavailableavailablechangespanincrementavailableavailablechangespanincrement PE*as%PEas%PEas%(years)publicPEas%PublicPEas%publicPEas%(years)PEasPPP$PEasPPP$PEasPPP$(years) ofTHE**ofTHEofTHEofTPE***ofTPEofTPEpercapitapercapitapercapita ArmeniaN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A AzerbaijanN/A26.22010N/AN/AN/A32.9200020.42009−12.59−1.39N/AN/AN/AN/AN/A Belarus12.11990212012+8.9220.4020.4199044.82012+24.4221.11N/AN/AN/AN/AN/A Bosniaand Herzegovina8.9198027.42011+18.5310.6052.5200956.72011+4.222.10N/AN/AN/AN/AN/A BulgariaN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A CroatiaN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A CzechRepublic211990202011−1.021−0.0589199062.52011−26.521−1.26$115.21990$394.22011+$279.021$13.29 Estonia19.5199921.52012+2.0130.1540.8199949.22012+8.4130.65$100.41999$279.82011+$179.412$14.95 Georgia45.6200041.22011−4.411−0.40N/AN/AN/AN/AN/AN/AN/AN/AN/AN/A Hungary27.6199133.42011+5.8200.2979.31991492011−30.320−1.52$158.61991$5642011+$405.420$20.27 Kazakhstan6.819912.82000−4.09−0.448.319911.61997−6.76−1.12N/AN/AN/AN/AN/A Kyrgyzstan10.9199011.22002+0.3120.039.919929.9199200N/AN/AN/AN/AN/AN/A Latvia21.9200524.22010+2.350.4631.3200538.42010+7.151.42N/AN/AN/AN/AN/A Lithuania32.9200424.922011−7.987−1.1434.96200434.222011−0.747−0.11N/AN/AN/AN/AN/A MontenegroN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A Poland28.4200222.52011−5.99−0.6638.4200239.42011+1.090.11$207.92002$326.32011+$118.49$13.16 Republicof Moldova7.94199132.92012+24.96211.199.119936.42012−2.719−0.14N/AN/AN/AN/AN/A RomaniaN/A201998N/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A Russian FederationN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A Serbia11.83199831.3201119.47131.5050.4200344.72011−5.78−0.71N/AN/AN/AN/AN/A Slovakia34199927.42011−6.612−0.5576.2199969.42011−6.812−0.57$203.81999$5252011+$321.212$26.77 Slovenia20.9200219.52011−1.49−0.1661.5200255.92011−5.69−0.62$355.32002$471.32011+$116.09$12.89 Tajikistan13199110.52003−2.512−0.21N/AN/AN/AN/AN/AN/AN/AN/AN/AN/A TFYRMacedonia13.8198014.92004+1.1240.05N/AN/AN/AN/AN/AN/AN/AN/AN/AN/A TurkmenistanN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/AN/A UkraineN/A4.22009N/AN/AN/A95.3199334.92005−60.412−5.03N/AN/AN/AN/AN/A UzbekistanN/A11.62001N/AN/AN/A6.419933.41999−3.06−0.50N/AN/AN/AN/AN/A MEAN20.021.73.014.70.0843.336.5−6.810.6−0.47$190.2$426.8$236.613.8$16.89 STDEV10.69.69.46.90.6428.921.218.66.61.60$92.1$112.4$117.75.3$5.58 MIN6.82.8−8.05.0−1.146.41.6−60.40.0−5.03$100.4$279.8$116.09.0$12.89 MAX45.641.225.031.01.5095.369.424.422.02.10$355.3$564.0$405.421.0$26.77 MEDIAN20.222.00.712.50.0438.439.4−3.09.0−0.53$181.2$432.8$229.212.0$14.12 **PE,Pharmaceuticalexpenditure. **THE,Totalhealthexpenditure. ***TPE,Totalpharmaceuticalexpenditure.
respective groups. Notable exceptions from this rule are Romania and Russian Federation. Russia was classified as a high income economy by the World Bank since August 2013 and as one of top performing emerging BRICS markets (The World Bank, 2015;
Jakovljevic, 2016). Due to these facts we would like to limit our results and conclusions on the rest of Eastern European region as thus there is higher degree of homogeneity. Countries presented in the observed sample (20 of historical free market and 18 of centrally planned economies) are geographically scattered throughout the respective European regions. Therefore, we still regard observed sample of countries to be representative of broad long term trends in pharmaceutical spending in the European Region.
CONCLUSION
The two observed broad groups of countries, former centrally planned and free market economies, share profoundly different historical legacies in medicines provision and financing mechanisms (Mossialos et al., 2004). This data report provides insight into the existence of two distinctively different pathways in spending on drugs over past several decades in the East and West of Europe. National policies sharing public reimbursement, insurance based mechanisms and out-of-pocket spending appear to be headed in two different directions (Mackenbach, 2006).
Eastern European states struggle with affordability issues and unequal access to medicines mostly determined by household income groups. Single most concerning fact is that transitional economies contracted their public share of pharmaceutical expenditure for almost half of percentage over the long course of years. Traditional free market economies, primarily EU-15 states mostly achieved better protection for their poor and vulnerable patient groups including those suffering from rare diseases and
those requiring expensive treatment strategies (Iskrov et al., 2012). Nevertheless, we must point out the huge progress that was made in Eastern Europe providing access to the innovative medicines to the broad layers of population (Putrik et al., 2014).
Pace of annual increase in per capita spending on medicines in PPP terms, was at least 20% faster in Eastern Europe compared to their Western counterparts. During the same years CEE region was expanding their pharmaceuticals share of health spending in eight fold faster annual rate compared to the EU 15. Current difficulties to withstand pressures arising from population aging and prosperity diseases remain primary challenge for sustainable funding of medicines provision in all of Europe (Ogura and Jakovljevic, 2014; Jakovljevic and Milovanovic, 2015; Jakovljevic and Laaser, 2015). Although differences remain we believe that at some point in future, these regions will converge increasing social welfare and affordability of medicines to the ordinary citizens (Deacon, 2000).
AUTHOR CONTRIBUTIONS
MJ and TK developed research questions, designed the study and drafted most of the manuscript. ML and OM took part in data acquisition, mining and analysis and prepared the tables and figure. All four authors revised draft and contributed essentially to the final appearance of the manuscript.
ACKNOWLEDGMENTS
The Ministry of Education Science and Technological Development of the Republic of Serbia has funded this study through Grant OI 175014. Publication of results was not contingent to Ministry’s censorship or approval.
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Conflict of Interest Statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Copyright © 2016 Jakovljevic, Lazarevic, Milovanovic and Kanjevac. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.
No use, distribution or reproduction is permitted which does not comply with these terms.
doi: 10.3389/fphar.2017.00314
Edited by:
Mihajlo Jakovljevic, University of Kragujevac, Serbia Reviewed by:
Thomas Michael Schmid, Kempten University of Applied Sciences, Germany Robert L. Lins, Retired, Antwerp, Belgium
*Correspondence:
Evelien Moorkens [email protected]
†These authors have contributed equally to this work.
Specialty section:
This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology
Received: 16 March 2017 Accepted: 12 May 2017 Published: 08 June 2017 Citation:
Moorkens E, Meuwissen N, Huys I, Declerck P, Vulto AG and Simoens S (2017) The Market of Biopharmaceutical Medicines: A Snapshot of a Diverse Industrial Landscape. Front. Pharmacol. 8:314.
doi: 10.3389/fphar.2017.00314
The Market of Biopharmaceutical Medicines: A Snapshot of a Diverse Industrial Landscape
Evelien Moorkens1*, Nicolas Meuwissen1, Isabelle Huys1, Paul Declerck1, Arnold G. Vulto2 †and Steven Simoens1 †
1Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium,2Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, Netherlands
Background: Biopharmaceutical medicines represent a growing share of the global pharmaceutical market, and with many of these biopharmaceutical products facing loss of exclusivity rights, also biosimilars may now enter the biopharmaceutical market.
Objectives: This study aims to identify and document which investment and development strategies are adopted by industrial players in the global biopharmaceutical market.
Methods:A descriptive analysis was undertaken of the investment and development strategies of the top 25 pharmaceutical companies according to 2015 worldwide prescription drug sales. Strategies were documented by collecting data on manufacturing plans, development programs, acquisition and collaboration agreements, the portfolio and pipeline of biosimilar, originator and next-generation biopharmaceutical products. Data were extracted from publicly available sources.
Results: Various investment and development strategies can be identified in the global biopharmaceutical market: (a) development of originator biopharmaceuticals, (b) investment in biotechnology, (c) development of next-generation biopharmaceuticals, (d) development of biosimilars, (e) investment in emerging countries, and (f) collaboration between companies. In the top 25 pharmaceutical companies almost every company invests in originator biopharmaceuticals and in biotechnology in general, but only half of them develops next-generation biopharmaceuticals. Furthermore, only half of them invest in development of biosimilars. The companies’ biosimilar pipeline is mainly focused on development of biosimilar monoclonal antibodies and to some extent on biosimilar insulins. A common strategy is collaboration between companies and investment in emerging countries.
Conclusions:A snapshot of investment and development strategies used by industrial players in the global biopharmaceutical market shows that all top 25 pharmaceutical companies are engaged in the biopharmaceutical market and that this industrial landscape is diverse. Companies do not focus on a single strategy, but are involved in multiple investment and development strategies. A common strategy to market biopharmaceuticals is collaboration between companies. These collaborations can as well be used to gain access in regions the company has less experience with. With
patents expiring for some of the highest selling monoclonal antibodies, this snapshot highlights the interest of companies to invest in the development of these molecules and/or enter into collaborations to create access to these molecules.
Keywords: Off-patent biological medicine, biosimilar medicine, investment and development strategies, biopharmaceutical market, pharmaceutical industry
INTRODUCTION
Totaling US$ 228 billion in global sales in 2016 (Troein, 2017), biopharmaceutical medicines represent a growing share of the global pharmaceutical market. With many of these biopharmaceutical products facing loss of patent protection and other exclusivity rights, also non-innovator versions of these molecules, biosimilars, may now enter the market, resulting in a shift of market shares (IMS Health, 2016), revision of strategies of companies and attraction of new players to the biopharmaceutical market. Due to lower research and development costs and increase in competition, biosimilars offer a lower cost alternative to expensive biopharmaceutical therapies.
By adopting biosimilars, health care systems can expand patient access, offer more treatment options to physicians and have a new tool to control increasing health care expenses (IMS Institute for Healthcare Informatics, 2016). Overall, large investments have been made by companies to compete on the biopharmaceutical market.
These developments are also reflected in the industrial players in this market. Although there does not exist a classification system of companies active in this market, one could distinguish between big pharmaceutical companies, biotechnological companies, generics companies, new entrants, and companies from emerging countries. Big pharmaceutical companies are companies like Pfizer, Merck, and J&J, which originally focused on chemically developed medicines, and now target the biopharmaceutical market. On the biopharmaceutical market, there are as well biotechnological companies, like Amgen, whose focus has been on the development of biopharmaceutical medicines, be it initially originator medicines and in a later phase biosimilar medicines. Generics companies, companies originally focusing on generics, have also entered the biosimilar market (e.g., Sandoz). New entrants are new biotechnological companies, such as Celltrion and Samsung Bioepis. Companies from emerging countries, like Biocon and Dr. Reddy’s, are companies in fast-developing economies.
The aim of this original research article is to identify and document which investment and development strategies are adopted by industrial players in the global biopharmaceutical market. To this effect, we distinguish between various investment and development strategies, and exemplify these strategies for the top 25 pharmaceutical companies. In 2012, Calo-Fernández et al.
identified different players active in the biosimilar industry and core capabilities to enter this market, supported by three case studies (Calo-Fernández and Martínez-Hurtado, 2012). To the best of the authors’ knowledge, our study is the first to provide a comprehensive snapshot of the industrial landscape of the biopharmaceutical and biosimilar market as of December 2016. It should be realized however that the landscape is rapidly evolving.
METHODS
A descriptive analysis was undertaken of the investment and development strategies of the top 25 pharmaceutical companies according to 2015 worldwide prescription drug sales (Evaluate Pharma, 2016; Pharm Exec, 2016). Identification of various investment and development strategies was based on previous research (Meuwissen, 2016). Identified strategies were further documented by collecting data on manufacturing plans, development programs, acquisition and collaboration agreements, the portfolio and pipeline of biosimilar, originator and next-generation biopharmaceutical products of these companies. Data were extracted from multiple, publicly available sources, including a review of the literature in PubMed and Embase over the last 5 years up to March 2016, a search of the reference list of included articles for other relevant studies, articles known to the authors, the website of the Generics and Biosimilars Initiative (GaBI) journal, GaBI Online, company and news websites. A detailed list with references consulted for each company is available from the authors on request.
RESULTS
Based on our analysis of industrial players in the global biopharmaceutical market, we distinguished between the following investment and development strategies:
(a) development of originator biopharmaceuticals, (b) investment in biotechnology, (c) development of next-generation biopharmaceuticals, (d) development of biosimilars, (e) investment in emerging countries, and (f) collaboration between companies. Table 1 shows the investment and development strategies of the top 25 pharmaceutical companies.
It shows whether the company is an originator company, whether they invest in biotechnology via investment in their own development program, via acquisition of biotechnological companies, or both. The table also shows involvement in development of generation biopharmaceuticals. A next-generation biopharmaceutical is created by modifying the structure of an existing biological molecule (via e.g., pegylation, glycosylation) to alter pharmacokinetic or pharmacological properties, such as half-life or bioavailability or to improve its safety profile e.g., by reducing immunogenicity. This definition of next-generation biopharmaceuticals does not include new dosage forms. Subsequently, the table shows involvement in biosimilar development. Importantly, the term biosimilar is only applicable when strict regulatory requirements (European Medicines Agency (EMA), Food and Drug Administration (FDA) guidelines) are in place in the region in which it has been approved. Table 1 also shows, the presence and investment of
TABLE1|Top25pharmaceuticalcompaniesrankedby2015worldwideprescriptiondrugsalesandexamplesoftheirinvestmentanddevelopmentstrategiesintheglobalbiopharmaceuticalmarketasofDecember 2016. Rank (6,7) CompanyStrategybiopharmaceuticalmarket (a)Developmentof originator biopharmaceuticals
(b)Investmentinbiotechnology(c)Developmentof next-generation biopharmaceuticals
(d)Developmentof biosimilars(e)Investmentinemerging countries(f)Collaborationand co-marketing OwndevelopmentprogramAcquisition 1Pfizer◦Genotropin®/ Genotonorm®- somatropin ◦Prevnar13®
◦InvestmentinGlobal BiotechnologyCenterChina ◦Investmentinnewbiologics clinicalmanufacturingfacility (expansionexistingsite)in Andover(US) ◦Plansexpansionbiologics plantDublin(Ireland) ◦ExpansionplantAdelaide (Australia)toproduce biosimilarpegfilgrastim
◦Medivation(2016) ◦Hospira(2015) ◦Wyeth(2009)
◦Developmentof next-generationhuman growthhormonein collaborationwith OPKO
◦ViaHospira: ◦Epoetinzeta(Retacrit®) ◦Filgrastim(Nivestim®) ◦Infliximab(Inflectra®) ◦Pipeline:adalimumab, bevacizumab,infliximab (outsideEEA),rituximab, trastuzumab,pegfilgrastim(via Hospira)biosimilars
◦Productionfacilitiesandsale China(biosimilars),Russia◦Celltrion(biosimilar infliximab) ◦MerckKGaA(avelumab) ◦OPKO(long-actinghuman growthhormone) 2Novartis◦Lucentis®-ranibizumab ◦Xolair®-omalizumab ◦Simulect®-basiliximab ◦Cosentyx®- secukinumab
◦Newbiologicsproduction plantSingapore ◦ExpansionCenterof BiotechnologyHuningue (France) ◦Investmentinbiologics manufacturingsites SchaftenauandKundel (Austria)
◦AdmuneTherapeutics (2015)– ◦Albinterferonalfa-2b (Joulferon®)(withdrawn frommarket)
◦ViaSandoz,thegenericsand biosimilarsdivisionofNovartis: ◦somatropin(Omnitrope®) ◦epoetinalfa(Binocrit®) ◦filgrastim(Zarzio®/Zarxio®) ◦etanercept(Erelzi®) ◦ViasubsidiaryHexal: ◦epoetinalfa(Epoetinalfa Hexal®) ◦filgrastim(FilgrastimHexal®) ◦Pipeline:infliximab(Sandoz acquireddevelopmentand commercializationrightsfor EEAfromPfizer),rituximab, adalimumab,pegfilgrastim biosimilars
◦Expandingpresencein emergingmarketsofAsia, AfricaandLatinAmerica
◦Genentech(developmentof Lucentis®andXolair®) ◦Xencor(bispecificantibodies) 3Roche◦MabThera®/ Rituxan®-rituximab ◦Avastin®-bevacizumab ◦Herceptin®- trastuzumab ◦RoActemra®- tocilizumab ◦Perjeta®-pertuzumab ◦Gazyva®- obinutuzumab
◦Investmentinincreased manufacturingcapacityat sitesinVacaville(Genentech) andOceanside(US),and Penzberg(Germany) ◦Constructionantibody-drug conjugatemanufacturing facilityBasel(Switzerland)
◦AdheronTherapeutics (2015) ◦InterMune(2014) ◦Genentech(2009)
◦Methoxypolyethylene glycol-epoetinbeta (Mircera®) ◦Peginterferonalfa-2a (Pegasys®)
–◦Chinafor,amongstothers, oncologytreatments ◦The‘BlueTree’cancerpatient supportinitiativeIndia ◦RochePharmaAfricaStrategy toimproveaccessto treatmentinSub-Saharan Africa,focusonhepatitisand cancerinwomen ◦
◦ChugaiPharmaceutical (Japan) ◦PierisPharmaceuticals (Cancerimmunotherapy) (Continued)
TABLE1|Continued Rank (6,7) CompanyStrategybiopharmaceuticalmarket (a)Developmentof originator biopharmaceuticals
(b)Investmentinbiotechnology(c)Developmentof next-generation biopharmaceuticals (d)Developmentof biosimilars (e)Investmentinemerging countries
(f)Collaborationand co-marketing OwndevelopmentprogramAcquisition 4MerckUS(MSD)◦Keytruda®- pembrolizumab ◦IntronA®-interferon alfa-2b ◦Severalvaccines
◦Investmentvaccine manufacturingsiteCarlow (Ireland)toproduceoncology biologics(Keytruda®) ◦Newbiologicsfacilityatsitein Cork(Ireland) ◦Newmanufacturingfacilityin Hangzhou(China)
◦cCAMBiotherapeutics (2015)◦Peginterferonalfa-2b (PegIntron®) ◦Corifollitropinalfa (Elonva®)
◦Pipeline:Viacollaboration SamsungBioepis,e.g.,insulin glargine,adalimumab, trastuzumabbiosimilars
◦Undertakingopportunitiesto expandinemergingmarkets (China,India,Brazil,Russia)
◦SamsungBioepis (developmentofbiosimilars, commercializationof infliximabbiosimilar [worldwideex-EU/Russia/ Turkey]andetanercept biosimilar[worldwideex-US/ EU/Japan]) ◦J&J(commercialization Remicade®;Simponi®via Schering-Plough) ◦Ablynx(nanobodies) ◦HanwhaChemical (developmentand commercializationetanercept biosimilar) 5Sanofi◦Lovenox®-enoxaparin ◦Lemtrada®- alemtuzumab ◦Zaltrap®-ziv-aflibercept ◦Vaccines(via Sanofi-Pasteur)
◦ExpansionbiologicssiteGeel (Genzyme,Belgium)to manufacturemAbs ◦InvestmentGenzyme productionfacilityFramingham (US)
◦ShanthaBiotechnics(2013) ◦Genzyme(2011)◦Insulin glargine-Lantus® ◦insulinglulisine -Apidra®
◦Pipeline:insulinlispro biosimilar◦FocusonChina ◦ViaacquisitionofShantha Biotechnics(focusvaccines) ◦Increasinginsulinproductionin Russia
◦Regeneron (Zaltrap®-aflibercept) 6GileadSciences◦Macugen®-pegaptanib ◦Lexiscan®- regadenoson
◦Acquisitionofbiologics manufacturingplantin Oceanside(US)from Genentech
◦ArrestoBiosciences(2011)––– ◦Nospecificeffortsfor biopharmaceuticals,focuson HIVtreatments
– ◦Notforbiopharmaceuticals, focusonHIVtreatments 7Johnson& Johnson◦Remicade®-infliximab ◦Eprex®/Erypo®- epoetinalfa ◦Simponi®-golimumab ◦Stelara®-ustekinumab
◦Biologicsmanufacturingsite Cork(Ireland) ◦Biologicsmanufacturingsite Leiden(TheNetherlands)
◦Crucell(2010) ◦Centocor(1999)––◦Globalpolicytosupport accessinemergingmarkets aswell
◦MSD(Remicade®, Simponi®) ◦Genmab(bispecific antibodies) ◦BavarianNordic(Ebola vaccine) 8GlaxoSmithKline◦Benlysta®-belimumab ◦Bexxar®-tositumomab ◦Multiplevaccins
◦Investmentvaccines manufacturingsiteTuas (Singapore) ◦InvestmentsinUK manufacturingnetwork ◦NewUSvaccinesR&Dcenter
◦GlycoVaxyn(2015) ◦HumanGenomeSciences (2012) ◦CellZome(2011)
◦Albiglutide (Eperzan®/Tanzeum®)–◦Increasinginvestmentin emergingmarkets,biggest areasofgrowth
◦Genmab(Arzerra®- ofatumumab;rightsnow transferredtoNovartis) ◦OncoMed(development oncologydrugs) (Continued)
TABLE1|Continued Rank (6,7) CompanyStrategybiopharmaceuticalmarket (a)Developmentof originator biopharmaceuticals
(b)Investmentinbiotechnology(c)Developmentof next-generation biopharmaceuticals (d)Developmentof biosimilars (e)Investmentinemerging countries
(f)Collaborationand co-marketing OwndevelopmentprogramAcquisition 9AstraZeneca◦Synagis®-palivizumab ◦Vaccines◦Constructionbiologicsplant Södertälje(Sweden) ◦Investmentbiologics productionfacilityFrederick (US) ◦Acquisitioncommercial biologicsmanufacturingsite Boulderandsupporting warehouseLongmont(US)
◦Spirogen(2013) ◦MedImmune(2007) ◦CambridgeAntibody Technology(2006)
◦Viabiologicsarm: MedImmune◦Pipeline:rituximab, bevacizumabbiosimilars◦Areaoffocus,specifically China◦SamsungBioLogics(joint venture:ArchigenBiotech, developmentrituximab biosimilar) ◦FujifilmKyowaKirin Biologics(development bevacizumabbiosimilar) ◦MSD(Manufacturing capacitysharing) ◦Celgene(durvalumab development) ◦EliLilly(immuno-oncology drugs) ◦ModernaTherapeutics (immuno-oncologymRNA therapeutics) ◦Regeneron(antibody-drug conjugates) ◦Inovio(cancervaccines) 10AbbVie◦Humira®-adalimumab ◦Synagis®-palivizumab◦Newmanufacturingfacility Tuas(Singapore)◦Stemcentrx(2016) ◦Pharmacyclics(2015)––◦AbbViewillfocuson expandingpresencein emergingmarkets ◦Viamanufacturingplant Singapore
◦BoehringerIngelheim (immunologydrugs) ◦Bristol-MyersSquibb (oncology) 11Amgen◦Blincyto®- blinatumomab ◦Enbrel®-etanercept ◦Epogen®-epoetinalfa ◦Neupogen®-filgrastim ◦Prolia®/Xgeva®- denosumab ◦Repatha®-evolocumab ◦Vectibix®- panitumumab
◦Severalproductionfacilities focusedonbiologics ◦Newmanufacturingfacility Tuas(Singapore) ◦Severalbiopharmaceutical medicinesinpipeline(e.g., monoclonal/bispecific antibodies,fusionproteins)
◦Micromet(2012) ◦BioVexGroup(2011)◦Darbepoetinalfa (Aranesp®) ◦pegfilgrastim (Neulasta®)
◦Adalimumab(Amjevita®) ◦Pipeline:trastuzumab, bevacizumab,infliximab, rituximab,cetuximab
◦Plansforincreasedpresence inkeynewandemerging markets(e.g.,China,Latin America,MiddelEast;via collaborations) ◦ViaDrReddy’s(India)
◦Allergan/Actavis(biosimilar monoclonalantibodiesfor oncology) ◦DaiichiSankyo(biosimilars) ◦DrReddy’s (commercializationXgeva®, Vectibix®andProlia®inIndia) ◦UCB(romosozumab) ◦Advaxis(cancer immunotherapy) ◦Xencor(cancer immunotherapyand inflammation) 12Allergan◦Botox®- onabotulinumtoxinA◦Biosimilardevelopmentcenter Liverpool(UK)◦RetroSenseTherapeutics (2016) ◦MotusTherapeutics(2016)
–◦Pipeline:Biosimilarprogram foroncology(Amgen)◦Presenceinallcontinentsof theworld ◦ActivelyinvestinginSouth Korea,China,Poland,Turkey, Philippines,SouthAfrica, Russia,IndonesiaandVietnam
◦Amgen(biosimilar monoclonalantibodies foroncology) ◦MolecularPartners (DARPin-basedproducts) (Continued)
TABLE1|Continued Rank (6,7) CompanyStrategybiopharmaceuticalmarket (a)Developmentof originator biopharmaceuticals
(b)Investmentinbiotechnology(c)Developmentof next-generation biopharmaceuticals (d)Developmentof biosimilars (e)Investmentinemerging countries
(f)Collaborationand co-marketing OwndevelopmentprogramAcquisition 13Teva Pharmaceutical Industries
◦Cinqair®-reslizumab ◦Granix®-tbo-filgrastim◦Investmentbiotechnological productionsiteUlm(Germany)◦Labrysbiologics(2014) ◦CoGenesys(2008)◦Lipegfilgrastim (Lonquex®) ◦Developmentof next-generationhuman growthhormone
◦Filgrastim(Tevagrastim®) ◦follitropinalfa(Ovaleap®) ◦filgrastim(Ratiograstim®)via acquisitionRatiopharm
◦ViaTevaGrowthMarkets◦Celltrion(biosimilars,e.g., trastuzumab,rituximab commercializationinUSand Canada) ◦Regeneron(fasinumab) 14NovoNordisk◦Severalinsulins ◦Norditropin®- somatropin ◦Novoseven®- recombinantfactor VIIa ◦NovoEight®- recombinantfactor VIII ◦Novo Thirteen®-recombinant factorXIII
◦Expansionproductionfacilities USandDenmarkfordiabetes portfolioandhemophilia treatments
◦Calibrium(2015) ◦MB2(2015)◦Liraglutide (Saxenda®/Victoza®) ◦Insulindetemir (Levemir®) ◦Insulindegludec (Tresiba®) ◦Developmentof semaglutide(GLP-1 analog) ◦Developmentof next-generationhuman growthhormone –◦Corecapability:buildingand maintainingaleadingposition inemergingmarkets ◦InvestmentsinChinaand RussiaforR&D,production andsales ◦ChangingDiabetesfor Childrenprogram,training HCPinpoorestcountriesin theworld
◦Ablynx(nanobodies) ◦Xencor(bispecificantibodies) 15EliLilly◦Forteo®-teriparatide ◦Glucagon®-glucagon ◦Humulin®-insulin ◦Humatrope®- somatropin ◦Taltz®-ixekizumab ◦Cyramza®- ramucirumab ◦Lartruvo®-olaratumab ◦Portrazza®- necitumumab
◦Constructionofcommercial scalebiologicsfacilityCork (Ireland) ◦ExpansionLillyBiotechnology CenterSanDiego(US) ◦Continuousinvestmentin insulinproducingsites
◦SGXPharmaceuticals(2008) ◦ImCloneSystems(2008) ◦IcosCorporation(2007)
◦Insulinlispro (Humalog®) ◦Dulaglutide(Trulicity®)
◦Insulinglargine (Abasaglar®/Basaglar®)◦Emergingmarketsbusiness area ◦ChinaviaYabao Pharmaceuticalsfordiabetes ◦ChinaviaInnoventBiologics
◦BoehringerIngelheim (Abasaglar®) ◦AstraZeneca(MedImmune; immune-oncologydrugs) ◦Pfizer(tanezumab,chronicpain) ◦MerckKGaA(manufacturing andcommercialization cetuximabUSandCanada) 16Bayer◦Eylea®-aflibercept ◦Betaferon®-interferon beta-1b ◦Kogenate®-octocog alfa
◦ExpansionsitesGermanyand USforhemophilia-Aproducts◦DIREVOBiotech(2008) ◦Schering(2006)◦Development damoctocogalfapegol (pegylatedoctocogalfa)
–◦Increasingsalesinemerging markets◦Regeneron(afliberceptforeye diseases) ◦OncoMed(development oncologydrugs) ◦Compugen(developmentand marketingantibody-based cancertherapeutics) 17Bristol-Myers Squibb◦Orencia®-abatacept ◦Opdivo®-nivolumab ◦Yervoy®-ipilimumab ◦Empliciti®-elotuzumab ◦Nulojix®-belatacept
◦Expansionbiologics manufacturingfacilityDevens, Massachusetts(US) ◦Constructionofnew large-scalemanufacturing facilityinCruiserath(Ireland) ◦Establishmentof biomanufacturingprocess laboratoryDublin(Ireland)
◦Padlocktherapeutics(2016) ◦CormorantPharmaceuticals (2016) ◦iPierian(2014) ◦ZymoGenetics(2010) ◦Medarex(2009) ◦AdnexusTherapeutics (2007)
◦Developmentof pegylatedfibroblast growthfactor21 –◦ExpandingcapacityinChina ◦Partnershipagreementsin ChinaandSingapore,e.g., SimcerePharmaceutical Groupforabatacept ◦R&DcenterinBangalore (India)
◦AbbVie(oncology) ◦SamsungBioLogics(Production biopharmaceuticalsat South-Koreaplant) ◦Janssen(immuno-oncology) (Continued)