Defitelio highlights a regulatory fault line

US approval of Jazz Pharmaceuticals’ Defitelio must have come as a welcome relief after years of disappointments. But it also put the spotlight on another quirk: while this orphan disease drug lurched from one US setback to another it was already available in Europe.

Defitelio is not alone in having scored such an accolade, and a search of EvaluatePharma reveals some 80 projects that have secured the green light in the EU but not on the other side of the Atlantic. These include one blockbuster, and another that could breach the $1bn threshold by 2020 (see table below).

The current blockbuster – Novartis’s Galvus – looks unlikely ever to secure US approval owing to safety worries connected with liver enzyme elevations. This had also troubled EU regulators, though not excessively: the diabetes drug eventually got the go-ahead in 2008, and last year recorded global sales of $1.1bn.

Only yesterday another example of this divergence was seen when Newron’s safinamide – available in Europe for over a year – added a US complete response letter to its refuse-to-file missive of 2014 (Parkinson’s developers go one for two, March 30, 2016).

Safinamide does not appear in this analysis because its forecast sales are relatively insignificant. Not so the likes of Novo Nordisk’s Xultophy – predicted to become a blockbuster by 2020 – or PTC Therapeutics’ Duchenne muscular dystrophy drug Translarna.

Top 10 drugs available in Europe but not the US
Sales ($m)
Product Company EMA approval US status 2015 2020e
Xultophy Novo Nordisk Sep 2014 Filed 20 1,561
Galvus Novartis Nov 2008 Phase III 1,140 1,429
Translarna PTC Therapeutics Jul 2014 Phase III 32 692
Brimica Genuair AstraZeneca Nov 2014 Phase III 27 345
DuoResp Spiromax Teva Apr 2014 Phase III 45 323
Lyxumia Sanofi Feb 2013 Filed 42 240
Teysuno Otsuka Holdings Mar 2011 Phase III 243 203
Imvamune Bavarian Nordic Aug 2013 Phase III 12 194
Zinforo AstraZeneca Aug 2012 Phase II 106 192
Esmya Gedeon Richter Feb 2012 Phase III 56 166

In fact, Xultophy is one of two diabetes drugs in this top 10, the other being Sanofi’s Lyxumia.

The FDA sidelined Xultophy because of its Tresiba (basal insulin) element, which was delayed over three years ago owing to a cardiovascular signal. Meanwhile, Lyxumia, a GLP-1 agonist, was set back when the FDA said it wanted to see data from the Elixa outcomes study before approving.

Like safinamide Translarna got a rare US refuse-to-file letter; this came in February and stated that PTC’s filing was incomplete.

Back in 2011 Defitelio, approved in the US yesterday for treating a rare complication of stem cell transplantation, was so badly knocked back by FDA requests that its then-developer, Gentium, withdrew the application before selling itself to Jazz. Defitelio was approved by the EMA in 2013 after several years’ sales as a “drug of last resort”.

At one point these disparities might have been seen as proof of the EMA’s soft touch versus its US opposite number. Since the EMA’s refusal to follow the US regulator’s lead on drugs like Kynamro and Belviq this is clearly no longer the case.

To contact the writers of this story email Jacob Plieth or Edwin Elmhirst in London at [email protected] or follow @JacobPlieth or @EPVantage on Twitter

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