March 01, 2016 Industry work on rare diseases continues to bear fruit Robin Davison The setbacks suffered by BioMarin, PTC Therapeutics and Sarepta in muscular dystrophy in recent months have not diminished the industry’s keenness to work in rare diseases. Indeed, this space, loosely defined as life-threatening, non-cancer orphan indications that require chronic treatment, remains one of the bright spots for the biotech industry. The exclusivity advantages and pricing power possible for companies that manage to develop orphan drugs give them favourable marketing economics, making for highly profitable products even if sales do not hit multi- blockbuster levels (see tables below). This is most evident at its most extreme, where there is an absence of payer pushback despite the very high prices of ultra-orphan conditions versus the charged rhetoric in not-so- rare therapy areas like hepatitis C. The rare disease space has recently seen the launch of three high-profile products (Alexion’s twin approval highlights industry’s love of orphans, June 26, 2015). These are Orkambi for cystic fibrosis from Vertex, Alexion's Strensiq for hyperphosphatasia and Kanuma for lysosomal acid lipase deficiency. All three are set to feature in the top 25 rare disease drugs by 2020, and indeed Orkambi looks set to reach second place in this league table with sales of just over $5bn, a shade under Alexion’s Soliris. EvaluatePharma consensus forecast for Soliris, which generated revenues of $2.6bn last year, suggests that sales will more than double over the next four years to $5.6bn. Top 25 rare disease products in 2020 Product Company Indication(s) 2020 sales ($) Soliris Alexion Pharmaceuticals PNH, aHUS 5,600 Orkambi Vertex Pharmaceuticals cystic fibrosis, F508del mutation 5,030 Esbriet Roche IPF 2,260 Advate Baxalta haemophilia A 1,867 Ofev Boehringer Ingelheim IPF 1,674 NovoSeven Novo Nordisk haemophilia A 1,600 Opsumit Actelion pulmonary hypertension 1,548 Sandostatin LAR Novartis acromegaly 1,269 Uptravi Actelion pulmonary hypertension 1,096 Kalydeco Vertex Pharmaceuticals Cystic fibrosis 1,054 Cerezyme Sanofi Gaucher's disease 1,051 Myozyme Sanofi Pompe's disease 959 Fabrazyme Sanofi Fabry disease 877 Samsca Otsuka hyponatraemia 870 Cinryze Shire hereditary angioedema 827 BeneFIX Pfizer haemophilia B 772 Eloctate Biogen haemophilia A 742 Promacta Novartis Thrombocytopaenia 736 Somatuline Ipsen acromegaly 709 Pulmozyme Roche cystic fibroris 696 Exjade Novartis iron overload, thalassemia 683 Prolastin-C Grifols AAT congenital deficiency 675 Kanuma Alexion Pharmaceuticals Liposomal acid lipase deficiency 670 Strensiq Alexion Pharmaceuticals Hyperphosphatasia 649 Elaprase Shire Hunter syndrome 645 Much of the Soliris growth is expected to come from new indications, based on phase III studies that are expected to report over the next year. The outcome of the Regain trial in generalised myasthenia gravis is due imminently, and results from Protect in delayed graft function and Prevent in neuromyelitis optica should come later in the year or in early 2017. Analysts at Leerink see Soliris sales rising further to $7.5bn by 2025 if results are positive. EP Vantage’s review suggests that a total of 11 rare disease products could achieve sales of $1bn or more by 2020, up from five currently. The top 25 has representation from both pharma and biotech sides of the industry with Sanofi, Novartis, Alexion and Shire, once it has completed its merger with Baxalta, each having three products, and Vertex and Roche represented with two each. These top 25 rare disease products will have combined sales of $34.5bn by 2020, around double their 2014 collective figure, representing compounded growth of 17% over the next four years, a level that is unlikely to be matched elsewhere in the pharma industry. R&D projects By 2020 there could also have been some new entrants from products that are currently in late R&D. Ranked by consensus sales this table is currently topped by PTC’s Translarna for Duchenne muscular dystrophy, although this is likely to change, given its recent regulatory setback. This leaves GW Pharmaceuticals’ Epidiolex as the top R&D rare disease asset. This is awaiting the outcome of four phase III trials in the difficult-to-treat childhood epilepsies Dravet and Lennox-Gastaut syndromes, with the first of these, in Dravet, expected to render results later this month. Top 10 rare disease R&D projects by forecast 2020 sales 2020 sales Product Company Indication(s) Status ($) Marketed (ex- Translarna PTC Therapeutics Duchenne muscular dystrophy 850 US) Lennox-Gastaut Syndome, Dravet Epidiolex GW Pharmaceuticals 721 Phase III Syndrome Eteplirsen Sarepta Therapeutics Duchenne muscular dystrophy 544 Filed Austedo Teva Huntington's disease 497 Filed CSL654 CSL haemophilia B 440 Filed Alnylam Patisiran amyloidosis 432 Phase III Pharmaceuticals NEOD001 Prothena amyloidosis 397 Phase III OCR-002 Ocera Therapeutics hepatic encephalopathy 369 Phase II BioMarin Pegvaliase PKU 345 Phase III Pharmaceutical SPK- Spark Therapeutics Leber's congenital amaurosis 326 Phase III RPE65 Rare disease specialists are not completely immune to the pressures felt throughout the sector – Alexion's shares have eroded at a rate similar to all of its Nasdaq brethren – but since these agents represent a much smaller share of payers' overall budgets than a new cholesterol drug, for instance, they are less likely to be subject to discount demands. If winter has indeed come for biopharma, companies like Alexion, Actelion and Vertex might be a comfortable place for investors to hunker down. To contact the writer of this story email Robin Davison in London at [email protected] or follow @RobinDavison2 on Twitter More from Evaluate Vantage Evaluate HQ 44-(0)20-7377-0800 Evaluate Americas +1-617-573-9450 Evaluate APAC +81-(0)80-1164-4754 © Copyright 2021 Evaluate Ltd..