The US FDA appears to have been seized by a bout of Christmas spirit. It has approved United Therapeutics' Orenitram, the oral form of the same company's pulmonary arterial hypertension (PAH) drug Remodulin (treprostinil), having already turned it down twice – an extremely unusual outcome, and one that drove the company's Nasdaq share price up 25%.
The decision is even more astonishing given that the application was unchanged from the previous one rejected by the agency (Oblivion beckons for Remodulin as FDA again says no, March 25, 2013). And the data backing the product are less than sparkling – even now, the drug's label explicitly states that its treatment effect is “small”. All in all, the approval is quite a coup for United, and has come in the nick of time, just before the patent on injected Remodulin expires next year.
While some analysts are predicting peak sales of up to $250m, uptake of the drug will depend on where it falls in the treatment cycle. It is approved only to improve exercise capacity in patients, rather than to treat PAH outright – unsurprising given that Orenitram has only shown an improvement in walking distance, rather than true clinical benefit.
Expansion in 2017?
To address this, a large study called Freedom-EV is under way, assessing its effects on morbidity and mortality with the aim of expanding the drug's approval.
On a conference call today, management said that enrolment would be complete by the end of 2015, leading to a filing for symptomatic control of PAH in 2016 and label expansion a year later. That, of course, will only occur if the trial data are positive, and Leerink Swann analysts put Freedom-EV's chances of success at just 25%. In any case United cannot expect the money to come in for some time yet.
Another limiting factor is that so far, Orenitram is labelled only as monotherapy, but PAH is normally treated with a combination of drugs. Orenitram is expected to show even less of an effect when used along with another vasodilator, according to the label.
The new extended-release tablet form is expected to eat into sales of the inhaled form of treprostinil, marketed as Tyvaso, as well as injected Remodulin. There is also a suggestion that insurers may not reimburse Orenitram if used as a combination, though management dismissed this on the call.
Furthermore, competition is growing. Bayer’s Adempas and Actelion’s Opsumit, also both oral, were both approved in the US in autumn and are set to take the number one and two positions in the PAH market in 2018, according to EvaluatePharma consensus data (Actelion to dominate PAH market, October 22, 2013).
And, worse, a new threat is approaching in the shape of Actelion's Selexipag, a phase III trial of which is due to read out in 2014. This trial, Griphon, has a clinical endpoint, and if it is successful, could pre-empt Freedom-EV and boost Selexipag at Orenitram's expense.
But for now the day belongs to United, the most unexpected success since Rudolph.