Alexion’s twin approval highlights industry’s love of orphans

The EU’s positive opinion earlier today for not just one but two of Alexion’s ultra-orphan drugs highlights the strength of a business model that is famously focused on the rarest of rare conditions.

No company has been as successful as Alexion in building a business based on treating severe and life-threatening diseases that affect just a few hundred patients globally, although many are copying its model (see tables below). However, an EvaluatePharma analysis suggests that this leading position will come under pressure over the coming years.

The two drugs that received EU backing today are Strensiq for paediatric-onset hypophosphatasia and Kanuma for lysosomal acid lipase deficiency and, when the formal approvals come through, Alexion will be transformed; it will have three products approved in four indications, versus its one product approved in two indications today.

Both are long-term enzyme-replacement therapies for life-threatening and ultra-rare metabolic disorders for which there are no other approved drugs. Strensiq has consensus projected 2020 sales of just over $800m and Kanuma $740m, according to EvaluatePharma consensus data.

Interestingly, they came to Alexion by acquisition: Kanuma through the recent $8.4bn purchase of Synageva, while Strensiq via a $470m deal for Enobia in 2011 (Alexion puts its stock to use at last, May 6, 2015). Though Strensiq was brought in at an earlier development stage than Kanuma, the marked disparity between these two transaction values does hint at an increasing valuation of orphan assets.

Two leaders

Alexion is one of the two leaders in the orphan disease, outside oncology, jostling for top spot with Sanofi-owned Genzyme, whose three venerable enzyme replacements – Cerezyme, Myozyme and Fabryzyme – have roughly the same sales revenue as Soliris in total. This analysis excludes oncology products, which are often approved in multiple orphan and non-orphan indications.

However, Alexion’s Soliris holds – and should retain until at least 2020 – the top position individually. Analysts collectively forecast that Soliris, which is approved for the two ultra-orphan indications paroxysmal nocturnal haemoglobinuria and haemolytic uremic syndrome, will see its sales rise by a compounded 16% a year over the next five years.   

Top 20 approved non-oncology orphan products
Sales ($m)
Product Indication Company 2014 2020
Soliris PNH, HUS Alexion 2,234 5,462
Esbriet Idiopathic pulmonary fibrosis Roche 48 2,350
Advate Haemophilia A Baxter 2,094 1,825
Opsumit Pulmonary hypertension Actelion 197 1,517
Xyrem Narcolepsy Jazz Pharma 779 1,476
Norditropin Short stature in children, adult GH deficiency Novo Nordisk 1,159 1,329
Kogenate Haemophilia A Bayer 1,473 1,101
Kalydeco Cystic fibrosis Vertex 464 1,059
Copaxone Multiple sclerosis Teva 4,237 1,022
Sylvant Castleman's disease Johnson & Johnson 16 1,006
FEIBA VH Haemophilia A Baxter 678 932
Translarna Duchenne muscular dystrophy PTC Therapeutics 1 927
Cerezyme Gaucher's disease Sanofi 950 922
BeneFIX Haemophilia B Pfizer 856 880
Cinryze Hereditary angioedema Shire 503 852
Myozyme Pompe disease Sanofi 720 814
Samsca hyponatremia Otsuka 190 799
Fabrazyme Fabry disease Sanofi 611 778
Eloctate Haemophilia A Biogen 58 743
Ampyra MS walking deficit Acorda 366 733

But, while Soliris should remain in top position of this analysis at the end of the decade, it will by be closely followed by Vertex’s cystic fibrosis combination Orkambi, which has forecast 2020 sales of $5.1bn, the data suggest.

Roche’s Esbriet is seen by analysts as coming in third position, with projected sales of $2.4bn. Roche obtained this product through its $8.3bn acquisition of InterMune last year, a deal which by comparison with that for Synageva now looks to have been a steal.

Top 15 late-stage non-oncology orphan programmes 
Product Indication Company Stage 2020 sales ($m)
Orkambi Cystic fibrosis, homozygous F508del mutation Vertex Filed 5,082
Uptravi pulmonary arterial hypertension Actelion Filed 1,165
VRS-317 Growth hormone deficiency Versartis Phase III 924
Strensiq Paediatric-onset hypophosphatasia Alexion Filed* 802
Kanuma lysosomal acid lipase deficiency Alexion Filed* 740
Drisapersen Duchenne muscular dystrophy, exon 51 BioMarin Filed 652
Gevokizumab Behçet's disease, pyoderma gangrenosum, non-infectious uveitis XOMA/Servier Phase III 638
Eteplirsen Duchenne muscular dystrophy, exon 51 Sarepta Phase III 544
Triheptanoin Glucose transporter type-1 deficiency syndrome Ultragenyx Phase II 485
Arikayce Non-tuberculous mycobacteria and P aeruginosa infections in CF Insmed Filed 485
Beloranib Prader-Willi syndrome Zafgen Phase III 482
Patisiran TTR-Mediated Amyloidosis Alnylam Phase III 402
n/a X-Linked Retinoschisis Applied Genetic Technologies Phase III 389
Epidiolex Dravet syndrome GW Pharmaceuticals Phase III 355
BAX 855/factor VIII Hemophilia A  Baxter Filed 338
*positive recommendation from EU’s CHMP. 

EP Vantage’s analysis does throw up a few anomalies – Teva’s Copaxone features for multiple sclerosis, while most other MS drugs do not. However, most of the remaining positions are held by products that address the traditional understanding of orphan indications such as the lysosomal storage disorders and muscular dystrophy.

One observation that is clear from the marketed product list is that many seem to enjoy a commercial longevity that would not be seen by traditional products in non-orphan indications. Sanofi’s Cerezyme was for example first approved in 1994.

These and other attractions of orphan drugs are well known. If a product meets the population-based requirements – addressing fewer than 200,000 patients in the US and 250,000 in the EU – it is conferred tax, market exclusivity and regulatory benefits. And this is not to mention the pricing and other commercial advantages that, while not legally enshrined, are also enjoyed.

A 2014EvaluatePharma report highlighted that orphan drugs, in this case including oncology, represented 14% in total 2014 pharmaceutical sales, a proportion that was projected to rise to 19% by 2020 (Orphan drug price rises indicate sector trends, November 5, 2014). The question has to be how much longer the pharmaceutical industry can continue to increase its focus on orphan relative to non-orphan indications. 

To contact the writer of this story email Robin Davison in London at [email protected] or follow @RobinDavison2 on Twitter

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