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pipeline watch Tamiflu SPCs expiries clear path in Europe I n several western European countries, mid-June will bring the expiries of supplementary protection certificates (SPCs) protecting the Tamiflu (oseltamivir) brand marketed by Roche for the treatment and prophylaxis of influenza. Those SPCs refer to European patent EP0,759,917, which is entitled ‘Novel selective inhibitors of viral or bacterial neuraminidases’ and expired in late-February last year. While these SPCs continue to cover Tamiflu for the next few weeks in Austria, Belgium, France, Greece, Italy, Luxembourg, the Netherlands, Spain and Sweden (see Figure 1), the brand’s protection is not universal. For example, in the UK, the local SPC GB02/047 held by Roche’s partner, Gilead, was withdrawn in September 2005. In May 2014, Actavis obtained a pan-European centralised marketing authorisation for generic oseltamivir capsules under the Ebilfumin brand name (Generics bulletin, 4 April 2014, page 15). Listed by the World Health Organization (WHO) as an essential medicine, Tamiflu is not far from being a blockbuster, with Roche posting global sales of the brand ahead by a tenth at constant exchange rates (CER) to SFr794 million (US$813 million) last year. However, the generic opportunity in Europe is relatively modest, with Roche’s annual brand sales in the region coming in at SFr101 million. Tamiflu has faced generic competition in the US since late last year after Alvogen in mid-December introduced the rival it had co-developed with India’s Natco Pharma (Generics bulletin, 16 December 2016, page 11). The first-to-market launch was the result of a patent- litigation settlement that Alvogen and Natco had struck with Roche that permitted market entry before the originator’s US patent 5,763,483 expired on 23 February 2017, including a six-month paediatric extension (Generics bulletin, 8 January 2016, page 14). The effect of Alvogen’s market entry is already telling on Roche. In the first quarter of this year, the Swiss originator saw its US Tamiflu turnover tumble by 39% to SFr156 million. This pushed down global sales of the antiviral brand by 27% to SFr270 million, as European sales slid by 30% to SFr13 million. Immediately upon the end of the paediatric extension to the US ‘483 patent in late February this year, the US Food and Drug Administration (FDA) approved a second oseltamivir abbreviated new drug application (ANDA) filed by Zydus Cadila’s Nesher affiliate (Generics bulletin, 3 March 2017, page 15). Amneal’s ANDA approval followed in mid-May. June also brings the expiry of SPCs through much of Europe for Swedish Orphan’s Orfadin (nitisinone), while AstraZeneca’s Crestor (rosuvastatin) loses its monopoly in Hungary and Switzerland. Looking at data exclusivity details recorded in its Ark Patent Intelligence database (see Figure 2), QuintilesIMS observes that Astellas’ Myrbetriq (mirabegron) treatment for overactive bladder will face the end of its US new chemical entity (NCE) exclusivity on 28 June. “Mirabegron is one of Astellas’ top drugs for overactive bladder treatment,” QuintilesIMS notes. Sales of the brand in Astellas’ Americas region increased by just over a third to US$510 million in its financial year ended 31 March 2017. Myrbetriq 25mg and 50mg extended-release tablets are protected by two patents listed in the FDA’s Orange Book that expire in August 2020 and March 2022, as well as by four other patents with November 2023 expiry dates. However, QuintilesIMS points out that several generics companies – including Actavis, Apotex, Lupin, Sandoz and Zydus Cadila – have already filed paragraph IV challenges to several listed patents. The FDA says it received the first paragraph IV challenge or challenges on 28 June 2016, the first date possible as it was one year before the end of NCE protection. Furthermore, the sole US patent listed against another of Astellas’ key overactive bladder brands, Vesicare (solifenacin succinate) tablets, expires on 19 November 2018. Under the terms of a litigation settlement over US patent 6,017,927, Teva can launch in October next year. G SPC expiries in June Data exclusivity expiries in June INNCountry INNCountry Abatacept AliskirenSwitzerland Norway, Switzerland Drotrecogin alfa (activated) Austria, France, Germany, Greece, Italy, Luxembourg, Slovenia, Sweden BelataceptTurkey FrovatriptanSwitzerland CyclizineAustralia MaropitantIreland Human C1 Esterase Inhibitor (Cinryze) Turkey MoxifloxacinSlovakia Hydroxycarbamide European Union Nitisinone Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Luxembourg, Netherlands, Norway, Spain, Sweden, UK LorcaserinUS Oseltamivir Austria, Belgium, France, Greece, Italy, Luxembourg, Netherlands, Spain, Sweden Rosuvastatin Hungary, Switzerland Figure 1: Molecules for which supplementary protection certificates (SPCs) expire in certain markets in June 2017 (Source – Ark Patent Intelligence) CabazitaxelCanada* Melatonin European Union MirabegronUS RufinamideCanada* Ustekinumab South Korea * This will be followed by a no-marketing period of two years during which a notice of compliance will not be granted to a generic manufacturer. Figure 2: Molecules for which data exclusivity expires in certain markets during June 2017 (Source – Ark Patent Intelligence) This monthly update of key patent, SPC and data exclusivity data is extracted from QuintilesIMS’ Ark Patent Intelligence Expiry Database. Covering 130 countries and over 3,000 INNs, Ark Expiry Database contains watertight data teamed with the ultimate in generic launch analysis. For further information, visit www.arkpatentintelligence.com or e-mail: [email protected]. 12 GENERICS bulletin 2 June 2017