The expression better late than never, rarely applies in the race to get new products to market. In the two years that Protalix BioTherapeutics’ has sought and failed to get approval for its Gaucher’s product any opportunity of making meaningful money in this niche area has almost certainly faded away. As such the group’s pending PDUFA date of May 1 for Uplyso, has lost much of the shine it might once have had.
This will be third time of asking for Uplyso, which in February 2010 and 2011 received approvable letters (Opportunity slipping from Protalix's grasp, February 28, 2011). Time had been of the essence then because if approved at first pass the drug would have been able to capitalise on the manufacturing issues that forced Genzyme, the producer of the only marketed product for the rare disorder, pull its product from the shelves leaving a gap in the market. Now it is hard to see where Uplyso will get its sales.
|% of market cap||52%|
|Date||May 1, 2012|
Thanks to issues with the regulator the supply gap in the Gaucher market was temporarily filed by Shire’s Vpriv as Genzyme struggled to get back up to full production levels, which it has now been achieved (Therapeutic focus - Spotlight falls on new Gaucher treatments amid Genzyme's woes, August 6, 2009).
This leaves Uplyso, which is partnered with Pfizer outside of Israel, coming third to the party. With such a small market - Credit Suisse estimates sales of about $900m annually - that now has two established products, Protalix will be forced to try to compete for newly identified patients, rather than capturing and keeping up those patients that had been left without supplies of Cerezyme.
As such, sales forecasts for Uplyso, which was never going to be a big seller anyway, have fallen dramatically over the last 12 months thanks to the approval delays. In January 2011 forecast sales for the drug in 2016 were $77m, in March this year that figure had more than halved to $32m.
Fear of the new
What has stymied Protalix’s attempts were the FDA questions on the chemistry, manufacturing and controls for the product. Extra scrutiny has been given to Uplyso, because unlike other products on the market, which are made from human and animal cells, Uplyso is made in plant cells that come from carrots.
While this method is more cost effective and potentially prevents the risk of infection from animal viruses, it has meant the FDA has examined it closely.
Interestingly, it is Uplyso’s novel manufacturing process that could ultimately help to achieve better than predicted sales. The use of plants, which makes the drug cheaper to produce might mean that the Protalix drug, which is partnered with Pfizer, will be able to compete on price.
But even if Uplyso is approved its economic superiority maybe short lived. Sanofi, is working on an oral treatment for Gaucher’s, called eliglustat tartrate. The drug, which was in-licensed from the University of Michigan, has just strated three phase III studies in over 350 Gaucher’s patients, including one study comparing the oral drug with infused Cerezyme.
In February, Sanofi also reported four-year follow-up data from patients enrolled in a phase II study. The long-term study showed sustained response and in some cases further improvements in a range of endpoints including, decreases in liver and spleen volumes and markers for bone disease.
An oral replacement for Cerezyme, which already claims 70% of the Gaucher’s market, could be a game changer. Not only would it be cheaper, and more convenient it would avoid the issues of patients developing antibodies to the infused enzyme, which currently happens in about 15% of Cerezyme users.
Analysts have forecast a launch for the drug by the end of 2013 and consensus sales for 2018 stand at $65m.
So while the approval of Uplyso in just over two week’s time would be a win for Protalix, the victory could be a small and potentially short-lived one.