Industry’s rare disease moves pay off

The pharmaceutical industry’s growing interest in orphan disease shows no sign of diminishing, and for good reason. The increased R&D investment in these indications in recent years has translated into a growing share of overall pharmaceutical sales, a new EvaluatePharma report finds. 

The drivers of this change include the favourable regulatory treatment of orphans, as well as market exclusivity and pricing advantages that make such drugs much more profitable than non-orphans. It is notable that the top 25 non-oncology orphan drugs in 2022 are expected to show a compounded growth of 18% over the next six years, almost three times the wider market average (see table below).

EvaluatePharma’s report, issued today to coincide with Rare Disease Day, suggests that orphan drugs collectively generated sales of $114bn in 2016, accounting for 16.4% of the global non-generic pharmaceutical market. This rises to $209bn by 2022, at which point these products will represent 21.4% of the overall market, a proportion that will have doubled in just over a decade.

If these sellside consensus forecasts are achieved orphan drugs will have shown a sales growth rate averaging 11.1% a year over the next six years – around double that of non-orphans.     

The report uses a definition of orphans that includes drugs first approved in an orphan indication or, where approved in more than one indication, that have more than 25% of their sales in orphan uses. Furthermore, cancer almost always meets the orphan criteria; oncology has different commercial characteristics from orphans in the more classical sense, though it is attractive to pharma for many of the same reasons.

Narrowed down

A narrowed definition, capturing only drugs that address chronic treatments for rare, life-threatening conditions outside oncology suggests that these top 25 orphans will have collective sales of $37.4bn in 2022, or around 3.8% of global pharmaceutical turnover. 

Of course this omits blockbusters that have a number of approved uses, most of which are not orphan. The narrower proportion should be watched carefully, as it gives a good indication of the overall sum spent on the very high-priced treatments for conditions such as cystic fibrosis and rare lysosomal diseases.

Top 25 orphan* drugs in 2022
Global sales ($m)
Product Company Indication  2016 2022e
Soliris Alexion  PNH, aHUS, (gMG) 2,843 5,139
Orkambi Vertex  Cystic fibrosis 980 3,634
Ofev Boehringer Ingelheim Idiopathic pulmonary fibrosis 763 1,827
Advate Shire Haemophilila A 1,258 1,740
HyQvia  Shire Primary immune deffiociency 258 1,714
Uptravi Actelion (J&J) Pulmonary arterial hypertension 249 1,679
Spinraza Biogen Spinal muscular atrophy 5 1,648
Sandostatin LAR Depot Novartis Acromegaly 1,646 1,624
Opsumit Actelion (J&J) PAH 843 1,546
Gammagard  Shire Primary immune deficiency 882 1,540
Xyrem Jazz Pharmaceuticals Narcolepsy 1,110 1,476
Emicizumab Roche Haemophilia 0 1,370
Samsca Otsuka  Hyponatraemia 451 1,167
Strensiq Alexion  Hyperphosphatasia  210 1,114
Lanadelumab Shire Hereditary angioedema 0 1,094
Fabrazyme Sanofi Fabry disease  746 1,071
Myozyme Sanofi Pompe disease  802 1,050
Cerezyme Sanofi Gaucher disease  828 979
SAGE-547 Sage Therapeutics Super refractory status epilepticus/postpartum depression 0 973
LentiGlobin Bluebird Bio Heamophilia 0 969
Epidiolex GW Pharma  Dravet/Lennox Gastaut syndrome 0 852
Kalydeco Vertex  Cystic fibrosis 703 849
Pulmozyme Roche Cystic fibrosis 695 792
Vimizim BioMarin MPS Type IV A (Morquio A syndrome) 354 778
Prolastin-C Grifols Emphysema 747 747
Note: *chronic treatments for rare, life-threatening conditions outside oncology. Source:EvaluatePharma.

There has been little or no pricing pressure in these areas so far, at least while they remain a single-digit percentage of overall pharmaceutical sales. But there is a concern that at some point the market will face pushback from payers, presumably when an untenable proportion of the budget is spent on a small proportion of patients.   

Alexion’s famous ultra-orphan Soliris remains the lead product in this category. Soliris, with sales of $3.7bn, ranks 27th overall in terms of all pharmaceutical products sales. But with the sellside consensus anticipating approval in generalised myasthenia gravis this is expected to rise to $5.1bn in 2022, by which point EvaluatePharma data suggest that it will have become the ninth-largest selling drug overall.

Competitive changes

Comparison with a similar analysis carried out last year highlights a surprising degree of movement between the top orphans (Industry work on rare diseases continues to bear fruit, March 3, 2016). For example, Roche’s Esbriet and Novo Nordisk’s NovoSeven, which both had prominent places in 2020 based on last year’s consensus data, now seem likely to disappear without trace in 2022, probably as a result of competitive changes in their indications.

And in recent months the orphan space has seen the launch of Biogen’s Spinraza for spinal muscular atrophy and Sarepta’s Exondys 51 for Duchenne muscular dystrophy. The former is expected to join the top 10 orphans by 2020, while the latter just makes the top 30. In a first for this space, however, both have seen US payers move to limit their use (Payers threaten a hard-knock life for orphan projects, January 25, 2017). 

Orphans, however they are defined, remain one of the brightest spots of pharmaceutical development, and the legislation framing them is widely claimed to have been a great success in public policy terms. However, there is a risk that before long orphans could face the same sort of pricing pressure as is common in non-orphan indications.

The EvaluatePharma Orphan Drug Report 2017 is available by free download.

To contact the writer of this story email Robin Davison at or follow @RobinDavison2 on Twitter

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