THERAPEUTIC FOCUS Rare Diseases “New and improved” has entered this space. Alongside the existing compounds that are transforming the lives of patients with orphan ailments, a wave of incrementally better products is coming out. Noah Pines reviews the signifi cant rare-disease market trends rphan Drugs 2.0 has arrived. Manufacturers in this space treatment arsenal has become crowded. Two other drugs for pulmo- are evolving their business models, from offering life-saving nary disorders recently scored approval, Bayer’s Adempas (riociguat) Otherapies to making available treatments that boost patient and United Therapeutics’s Orenitram, an oral form of the drug quality of life, as they seek to further normalize the lives of people Remodulin (treprostinil). The new PAH drugs also compete against living with rare diseases. Gilead’s Letairis (ambrisentan) and Pfi zer’s Revatio (sildenafi l). Over the past 30 years, thanks in part to government incentives Newer meds like Opsumit aim to not only lengthen patients’ and other measures, treatment options for patients with many ultra- lives, but also to help sufferers manage the ailment more easily. rare and severe, life-threatening diseases—patients who without Among the orphan drugs available, many are “rather good at sav- these therapies had no other hope—have multiplied. Today about ing people lives,” says Mike Hodgson, partner and chief creative 300 of the roughly 7,000 identifi ed rare diseases have treatments. offi cer, Cambridge BioMarketing. “What’s next is to help them live Many such therapies have become commercially successful. World- as normally as they possibly can.” wide sales for the top 50 orphan brands rose by 9% in 2012 to $69.9 The orphan-better trend got a push from provisions that if a billion, according to data from market research fi rm EvaluatePharma. product is clinically superior (i.e., more effective, safer or a major Recently, there has been a bifurcation into two different segments contribution to patient care), it can receive orphan designation, says of new drug candidates: those which are innovators, and those which Cote. The completely innovative compounds, he says, are now “going are better orphans. “We are seeing more and more drugs coming forward right alongside this secondary market trend of products to market that are improvements over those which exist,” says Tim that are...the same moiety, the same API, as the innovator, but dif- Cote, MD, MPH, former director of FDA’s Offi ce ferent in such a way that [they] meet clinical superiority criteria.” of Orphan Products Development and now an Highly engaged patient communities are also supporting devel- industry consultant. opment of these meds, as they have for other rare-disease drugs One example is Actelion’s Opsumit (maciten- (see sidebar). “These patients are able to articulate the true value tan), approved in October for pulmo- of these treatments,” says Peter Nalen, president/CEO of Compass nary arterial hypertension (PAH), Healthcare Marketers. “A drug taken twice a day vs. four times a a chronic, progressive and debilitat- day can be a meaningful difference, so that the parent who needs ing disease that can lead to death or to administer it to their child can actually sleep through the night. the need for lung transplantation. That is a real value to a mom, a dad or a kid, but that often does Patients on Opsumit don’t have not get looked at in the clinical trials.” to be monitored for liver safety, An example is Raptor’s enteric-coated Procysbi (cysteamine an advance over Actelion’s earlier bitartrate), for nephropathic cystinosis, approved in 2013. An PAH drug, Tracleer (bosentan). immediate-release tablet, Mylan’s Cystagon, was approved in 1994. While few alternatives for PAH Procysbi is a long-acting form that also offers fewer AEs than the existed a decade ago, today the initiator compound. 38 MM&M x FEBRUARY 2014 x mmm-online.com TOP RARE50 RARE DISEASE DISEASE PRODUCT PRODUCTS AREAS, 2012 MostCategory concentrated leaders, ranked orphan by drug 2012 categories, global sales, by their and numbertheir US of media FDA-approved spend products†, plus products’ sales (global) and media spend (US) US DTC US DTC US journalUS journal USUS sales sales $ $ Vs. Vs.prior prior TRx mediaVs. $ prior mediaVs. prior $ Vs. prior mediamedia $ $ Vs. prior Rank Product ManufacturerManufacturer (millions)(millions)* 12 mos.12 mos. (millions)*(000s)* 12 mos. (000s)**12 mos. 12 mos. (000s)*(000s)** 1212 mos.mos. H1 EMOPHIRituxanLIA Roche $7,155.3 5.4% $414.3 -12.2% $0.0 N/A 12 RefactoGleevec NovartisPfizer $4,675.0$5,440.0 -42.8%0.3% 87.4 $0.0-10.5% $0.0N/A N/A $0.0$0.0 -100.0%N/A 23 KogenateNeulasta AmgenBayer HealthCare $4,092.0$4,742.5 -40.8%3.5% 15.0 $802.3-44.7% >100.0%$20.5 -100.0% $586.2$0.0 N/A14.8% 34 Humate-PCopaxone TevaCSL Behring $3,996.0$3,757.5 -60.2%34.4% 14.3 $0.0-66.1% $96,832.0N/A -59.0% $0.0$346.5 -83.0%N/A 45 AlphaNineRevlimid CelgeneGrifols Biologicals $3,766.6$3,214.9 13.8%17.4% 65.4 $0.07.3% $0.0N/A N/A $1,001.7$0.0 N/AN/A 5 Novoseven Novo Nordisk $2,943.1 58.1% 32.5 19.6% $0.0 N/A $0.0 N/A 6 Avonex Biogen Idec $2,913.1 8.4% $369.7 >100.0% $900.0 2.9% 6 Desmopressin acetate Generic $2,518.3 9.8% 13.6 -10.2% $3,595.2 -6.0% $0.0 N/A 7 Alimta Eli Lilly $2,594.3 5.4% $6.1 -4.0% $698.5 >100.0% 7 Mononine CSL Behring 8 BeneFixRebif MerckPfizer KGaA $2,433.4$2,099.9 -20.3%3.4% 95.3 $3.21.8% $0.084.0% N/A $0.0$0.0 -100.0%N/A C9 HRONICAdvate MYE LOGENOUS LEUKEMIABaxter International $2,074.5 5.8% $0.0 N/A $193.5 9.8% 110 BosulifTracleer ActelionPfizer $1,600.5 -7.0% $0.0 N/A $0.0 -100.0% 211 GBetaseronleevec BayerNovartis $1,563.5 0.6% $0.0 N/A $0.0 -100.0% 312 RoferonNovoSeven A NovoRoche Nordisk $1,543.0 -1.0% $0.0 N/A $187.2 23.8% 413 SynriboKogenate BayerIVAX $1,519.8 1.6% $0.0 N/A $0.0 N/A 514 SprycelSandostatin LAR NovartisBristol-Myers Squibb $1,512.0 4.8% $2.5 >100.0% $63.9 -28.0% 6 Tasigna Novartis 15 Velcade Johnson & Johnson $1,500.0 17.7% $0.0 N/A $454.6 -71.5% CHRONIC LYMPHOCYTIC LEUKEMIA 16 Zometa Novartis $1,288.0 -13.4% $13.9 -53.0% $467.8 -52.2% 1 Rituxan Genentech/Roche 17 Neupogen Amgen $1,260.0 0.0% $0.0 N/A $0.0 N/A 2 Fludara Genzyme 318 FludarabineSutent phosphate PfizerGeneric $1,236.0 4.1% $0.8 -74.0% $181.1 -39.4% 419 CampathSoliris AlexionGenzyme $1,134.1 44.8% $0.0 N/A $413.9 84.6% 520 ArzerraSprycel Bristol-MyersGlaxoSmithKline Squibb $1,019.0 26.9% $5.5 -69.0% $379.8 -39.3% 621 TreandaNexavar BayerCephalon/Teva $1,018.3 0.9% $0.2 -68.0% $0.0 N/A P22U LMONARTasignaY ARTERIA L HYPERTENSIONNovartis $998.0 39.4% $0.0 -100.0% $35.0 -97.3% 123 TracleerNorditropin SimpleXx NovoActelion Nordisk $984.2$1,634.4 0.0%4.4% 6.5 $64.5-17.5% >100.0%$0.0 N/A $0.0$0.0 N/AN/A 2 Letairis Gilead $1,463.2 -23.5% 0.1 -67.5% $0.0 N/A $0.0 N/A 24 Sensipar Amgen $950.0 17.6% $0.0 N/A $0.0 -100.0% 3 Ventavis Actelion $1,394.1 -7.0% 5.4 -18.5% $165.9 -100.0% $1,794.1 52.0% 25 Lidoderm Endo Health $947.7 14.8% $32.4 -81.0% $0.0 -100.0% 4 Adcirca Eli Lilly $1,287.5 7.3% 5.3 -6.0% $25,210.6 -31.0% $929.5 334.0% 26 Temodar Merck & Co $917.0 -1.9% $0.0 N/A $0.0 -100.0% 5 Remodulin United Therapeutics $1,210.2 -13.2% 4.9 -27.9% $0.0 -100.0% $0.0 N/A 627 TyvasoVelcade TakedaUnited Therapeutics $881.9$1,184.1 -7.3%19.8% 9.6 $0.0-6.3% $0.0N/A N/A $0.0$0.0 N/AN/A LENNO28 ExjadeX-Gastaut SYNDROME Novartis $870.0 2.4% $0.0 N/A $0.0 N/A 129 FelbatolGenotropin PfizerMeda Pharma $832.0$1,168.6 -18.1%-6.4% 14.4 $0.0-4.8% $0.0N/A N/A $0.0$0.0 N/AN/A 230 LVidazaamictal CelgeneGlaxoSmithKline $823.2$1,108.1 12.0%16.7% 25.7 $0.049.2% $0.0N/A N/A $0.0$0.0 -100.0%N/A 331 TopamaxCerezyme SanofiJohnson & Johnson $813.9$967.4 103.5%32.6% 2.9 $0.077.1% $107,420.8N/A 43.0% $0.0$4,235.0 -28.0%N/A 432 OnfiAfinitor NovartisLundbeck $797.0$907.8 6.1%79.9% 5.4 $2.2-12.0% $0.0-66.0% N/A $2,496.2$0.0 >100.0%N/A 533 BanzelBeneFI X PfizerEisai $775.0$887.4 -16.7%11.8% 30.0 $0.00.8% $0.0N/A N/A $61.0$0.0 N/A-33.9% MULTIPLE SCLEROSIS 34 Yervoy Bristol-Myers Squibb $706.0 96.1% $1.7 >100.0% $133.9 -86.9% 1 Ampyra Accorda Therapeutics $773.4 3.6% 4.5 -13.8% $0.0 N/A $0.0 N/A 35 Valcyte Roche $680.6 5.8% $0.0 N/A $0.0 N/A 2 Avonex Biogen Idec $668.5 3.0% 3.1 -16.2% † N/A $0.0 N/A 336 BetaseronSuboxone ReckittBayer Benckiser HealthCare $646.1$616.3 31.3%-21.5% 7.7$1,227.9 25.3% >100.0%$0.0 N/A $176.6$0.0 N/AN/A 437 CopaxoneTreanda TevaTeva $608.0$610.4 >100.0%11.1% 1.4 $0.6-8.8% >100.0%$0.0 N/A $914.7$0.0 N/A-33.9% A38N GIOEDEMAHumate/HAE P CSL $605.2 2.2% $0.0 N/A $0.0 N/A 139 BerinertMyozyme P SanofiCSL Behring $594.0$595.1 42.0%38.6% 6.3 $0.019.5% $0.0N/A N/A $0.0$4,492.2 -24.0%N/A 240 CinryzeReFacto AF/Xyntha PfizerViroPharma $584.0$573.3 12.0%15.4% N/A $0.0N/A -100.0%$0.0 N/A $0.0$0.0 N/AN/A 341 FirazyrFEIBA VH BaxterShire International $575.3$560.4 13.4%2.9% 1.9 $0.02.0% $48.9N/A N/A $0.0$1,119.5 -100.0%-7.0% 442 KalbitorPulmozyme RocheDyax $572.9$539.1 -18.4%3.0% 12.6 $0.035.0% $0.0N/A N/A $0.0$0.0 N/AN/A CYSTIC FIBROSIS 43 Revatio Pfizer $534.0 -0.2% $0.0 N/A $0.0 N/A 1 Cayston Gilead $445.2 11.3% 2.3 -7.8% $0.0 -100.0% $0.0 N/A 44 Elaprase Shire $497.6 7.0% $0.0 N/A $0.0 N/A 2 Kalydeco Vertex $445.2 1.5% 1.8 -20.1% $0.1 -96.0% $0.0 N/A 345 TobiReplagal ShireNovartis $497.5$433.8 -12.8%4.7% 25.9 $0.0-3.0% $0.0N/A N/A $0.0$67.2 N/AN/A 446 PulmozymeHelixate CSLGenentech/Roche $485.2$411.4 67.9%-3.4% 1.5 $0.050.4% -100.0%$0.0 N/A $0.0$2,036.4 -57.0%N/A M47UCOPO RemodulinLYSACCARIDOSIS United Therapeutics $458.0 6.5% $0.0 N/A $0.0 N/A 148 AldurazymeEpadel MochidaBioMarin/Genzyme $450.0$388.8 3.0%-6.8% 4.5 $0.01.0% $0.0N/A N/A $0.0$0.0 N/AN/A 249 ElapraseTeysuno OtsukaShire Holdings $447.6$380.2 -7.7%-3.2% 0.1 $0.0-2.5% $0.0N/A N/A $0.0$209.7 N/AN/A 350 NaglazymeProlastin-C A1P1 GrifolsBioMarin $426.8$379.0 -18.1%71.0% 34.2 $0.0-6.0% $0.0N/A N/A $98.8$0.0 N/AN/A Sales, EvaluatePharma; DTC media spend, Nielsen; journals, Kantar Media.