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Fabio Pammolli, Massimo Riccaboni, Laura Magazzini, Mark Supekar

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Fabio Pammolli, Massimo Riccaboni, Laura Magazzini, Mark Supekar RAPPORTO 02/2009 NUOVE POLITICHE PER L ’INNOVAZIONE NEL SETTORE DELLE SCIENZE DELLA VITA Fabio Pammolli, Massimo Riccaboni, Laura Magazzini, Mark Supekar Si ringraziano: Claudio Cavazza, Anna Horodok, Francesco Macchi, Lucia Monaco, Adrian Towse e Cristina Tinti per il fondamentale contributo alla stesura di questo lavoro . INDICE EXECUTIVE SUMMARY ..................................................................................2 1. Risorse e innovazione: fallimenti di mercato e logiche di intervento pubblico ...........2 2. Da raro a generale: nuovi modelli di sostegno mission-oriented alla ricerca e sviluppo nelle scienze della vita ............................................................................. 31 2.1. Incentivi pubblici per la ricerca sulle malattie rare: il panorama internazionale .. 37 Stati Uniti .................................................................................................................... 37 Giappone ..................................................................................................................... 44 Australia ...................................................................................................................... 46 Unione Europea ........................................................................................................... 46 2.2. Incentivi pubblici per la ricerca sulle malattie rare: il panorama europeo ............ 58 Francia ........................................................................................................................ 58 Germania ..................................................................................................................... 60 Spagna ......................................................................................................................... 61 Olanda ......................................................................................................................... 63 Belgio .......................................................................................................................... 64 Finlandia ..................................................................................................................... 64 Italia ............................................................................................................................ 65 3. Da raro a generale: nuovi modelli competitivi nel settore delle scienze della vita .... 71 Genzyme ...................................................................................................................... 75 Orphan Europe ............................................................................................................ 78 Shire HGT .................................................................................................................... 80 4. La ricerca sulle malattie rare................................................................... 84 4.1. Dimensione del mercato e intensità di R&S ............................................................ 88 Rare ma numerose ...................................................................................................... 89 La relazione tra prevalenza e intensità di ricerca ................................................... 102 4.2. La ricerca italiana sulle malattie rare nel panorama internazionale ................... 108 La ricerca biomedica in Italia: uno sguardo d’insieme ............................................. 108 La ricerca biomedica in Italia: le malattie rare ........................................................114 4.3. Casi di eccellenza della ricerca biomedica italiana sulle malattie rare ............... 125 Emoglobinuria parossistica notturna ........................................................................ 127 Mesotelioma: l’esperienza MOLMED ......................................................................... 132 Telethon: terapia genica nel settore delle Malattie Rare e Ultra Orfane ............... 137 Le sindromi di Noonan e Leopard ............................................................................. 141 La Sindrome di Rett .................................................................................................. 146 Conclusioni........................................................................................... 150 Bibliografia........................................................................................... 159 Allegati ............................................................................................... 164 1 EXECUTIVE SUMMARY Il sistema di ricerca italiano, nelle sue componenti pubblica, privata e no profit, può contare su di un elevato indice di specializzazione relativa, con punte di assoluta eccellenza internazionale, nel settore delle malattie orfane (malattie rare, malattie tropicali) , mentre si palesano limiti strutturali nella disponibilità di infrastrutture e competenze post-genomiche avanzate. Questo rapporto raccomanda l’adozione di misure specifiche a sostegno della ricerca nel settore delle malattie orfane. Al di là delle motivazioni specifiche riferite al comparto, sia sul versante della domanda (carenza di incentivi all’investimento privato date le ridotte dimensioni dei mercati di riferiemto) che sul versante dell’offerta (presenza di fattori di potenziale vantaggio comparato per il nostro Paese), il rapporto evidenzia un ulteriore fattore distintivo riferito al settore delle malattie orfane: i benefici di un incremento dei livelli di investimento sulle malattie orfane è suscettibile di produrre conoscenze rilevanti per l’avanzamento della frontiera scientifica e tecnologica in aree più vaste delle scienze della vita. La ricerca su malattie orfane richiede e stimola lo sviluppo di capacità general purpose lungo tutta la filiera dell’innovazione, tra cui in particolare lo sviluppo di piattaforme tecnologiche di postgenomica e proteomica avanzate, la costruzione di banche dati biologiche e dello sviluppo di test diagnostici che vanno nella direzione dello sviluppo di medicinali personalizzati in base ad analisi farmacogenetiche, lo sviluppo di prodotti biologici, la sperimentazione di nuove modalità di conduzione di trial clinici, in considerazione dell'esiguo numero di pazienti trattati e di nuove tecniche di predizione in base a modelli sviluppati in ambito clinico, la scoperta di pathway genetici e di relazioni genotipo/fenotipo. L’attivazione di linee di ricerca stabili nel settore delle malattie neglette, oltre a sviluppare competenze tecnologiche avanzate può concorrere a stimolare la crescita di realtà aziendali ed industriali (PMI e grande industria) ben connesse a cluster pubblico- privati. Tale integrazione appare una condizione necessaria per realizzare quelle condizioni di massa critica necessarie per affrontare le nuove frontiere della medicina traslazionale e personalizzata, secondo le nuove tecniche farmacogenomiche e postgenomiche. La realizzazione di condizioni di massa critica è suscettibile di indurre ricadute socio- 2 economiche occupazionali, con la formazione di figure professionali dalla ricerca di base sino alla ricerca clinica e dello sviluppo farmaceutico, tradizionale e biotecnologico. Il valore aggiunto generato è suscettibile di essere trasmesso ad altri settori terapeutici di rilevanza primaria (oncologia, cardiovascolare, neurologia) o transettoriale, quali lo sviluppo di test diagnostici, dispositivi medici e componenti biomedicali. L’adozione di un piano basato sulla selezione e sul sostegno “technology push” di progetti finalizzati allo sviluppo di nuove terapie per le malattie orfane, se accompagnata da iniziative complementari di posizionamento delle piattaforme bioinformatiche, proteomiche e post-genomiche, può accellerare lo sviluppo di nuove terapie e sostenere la crescita e l’innovatività del settore biofarmaceutico. 3 Presupposti: il modello SCIENCE Il Rapporto identifica sette diverse ambiti di riferimento per la valutazione del posizionamento, delle prospettive strategiche e delle condizioni riferite alle diverse linee di intervento: (S) Servizi a valore aggiunto : erogazione agevolata di servizi di supporto organizzativo, finanziario, legale e manageriale, di produzione e di supporto all’accesso ai mercati di riferimento, ai pazienti e ai medici. (C) Clustering : presenza di una massa critica, accanto ai centri di eccellenza scientifica, di strutture cliniche, imprese biotecnologiche e farmaceutiche; (I) Incentivi : realizzazione di schemi di incentivazione rivolti alle strutture di ricerca, ai ricercatori e alle imprese che decidano di operare su progetti misson oriented finalizzati allo sviluppo di farmaci innovativi per la cura di patologie per le quali non si dispone di alcun trattamento efficace (malattie rare e malattie del Terzo Mondo); (E) Eccellenza scientifica : presenza di centri di ricerca pubblici e/o privati di livello internazionale in grado di formare e attrarre ricercatori e scienziati di chiara fama e di produrre ricerca di base di frontiera; (N) Network : complementarità, comunicazione e relazioni di collaborazione tra soggetti industriali, centri di ricerca biologica, chimica, informatica, centri di ricerca clinica e strutture ospedaliere, centralità nelle reti di collaborazione scientifica e di divisione del lavoro innovativo a livello nazionale ed internazionale; (C) Clinical Development : sostegno alla conduzione di studi clinici e alla condivisione dei risultati di tali studi lungo la filiere f rom bench to bedside e tra pubblico e privato (medicina traslazionale).
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