The FDA has decreed that Ruconest is to become the fourth therapy for hereditary angioedema (HAE) in the US, driving the shares of its originator, Pharming, up 15%. Despite this excitement, it is hard to see where Ruconest will fit in a crowded market where rival products offer prophylactic dosing or swifter delivery.
With this in mind, the drug’s US licensee will have a decision to make. Ruconest was always outside Salix Pharmaceuticals’ core focus, and after Salix’s purchase of three gastrointestinal drugs from Cosmo Pharmaceuticals last week it is even more of an outlier. With sales forecasts less than stellar, the US company might wonder whether the recombinant C1 esterase inhibitor is worth the bother.
“Despite the fact that this is something else [for Salix], and despite the fact that it is biological, which they are not so used to, they are really keen on this,” Sijmen de Vries, Pharming’s CEO, told EP Vantage.
He says this is because Ruconest, which Pharming sells in Europe under the name Rhucin, will go on to be approved and sold for bigger indications. It is already in phase II for prophylaxis of HAE, and Mr de Vries says that the following areas of development should be more within Salix’s comfort zone.
“Yes it’s a different thing, but drug approvals are rare in the US, and you should exploit them to the maximum. Salix is going to explore phase II in acute pancreatitis, which is right in their expertise area, and that is a huge indication compared to the HAE indications.”
Recombinant rabbit remedy
But it will take time to get approval for pancreatitis, and in the meantime Ruconest’s forecast HAE sales are lacklustre. Shire is forecast to dominate the market, with its preventive drug Cinryze and acute-treatment product Firazyr set to do $495m and $348m respectively in 2014, compared with $6m for Ruconest and $9m for the Rhucin brand, according to EvaluatePharma.
The picture does not change much in 2020; consensus analyst forecasts put Ruconest on $41m and Rhucin on $52m, behind Cinryze, Firazyr, BCX4161 from BioCryst Pharmaceuticals, CSL’s Berinert P and Dyax’s Kalbitor.
With a panoply of compounds already on the market and others on the way, it is tricky to see where Ruconest will fit. Mr de Vries dismissed this concern, saying that as it is recombinant – it is secreted in the milk of transgenic rabbits – the drug has an edge on safety. “The FDA has the opinion that recombinant products are inherently preferable to blood products, because they don’t carry plasma risks. Plasma C1 inhibitors have a warning for thromboembolic events.”
But Ruconest carries this warning too. Mr de Vries says this is because the FDA believes all drugs in this class carry this risk, and stresses that thromboembolism has never been seen with Ruconest so far.
It is also competitive on efficacy, Mr de Vries says, as the safe dose is higher. Published data show “consistently better responder rates versus Berinert P, which is our direct competitor”, though indirect comparison of this kind is less than perfect as an evaluation technique.
“Firazyr seems to work reasonably well on symptoms but it not only has moderate responder rates but also up to 30% of people on Firazyr take a second or a third shot. That’s very expensive because it’s $8-9,000 a shot. One shot does it, practically speaking, with Ruconest.”
Still, Firazyr has a notable advantage in its route of administration. It is subcutaneous, where Ruconest must be injected over a five-minute period – though fortunately this can be accomplished by the patient using a home infusion kit.
“Firazyr is selling like hot cakes, but that’s purely because it’s subcutaneous and it’s convenient,” Mr de Vries says. But some patients will still take a brief subcutaneous jab over an infusion, even if it has to be repeated.
Ruconest’s recombinant nature is an asset, as is the fact that it has US orphan drug status for both acute treatment and prophylaxis of HAE. Ultimately, though, its place in the market is not assured.