New FDA regulations could PEP up Eurand sales

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With the April 28 deadline for the withdrawal of all non-FDA approved pancreatic enzyme replacement products (PEPs) rapidly approaching, the field that has been unregulated for more than 70 years could find itself with only a couple of products left available for patient consumption.

Of the last men standing only Solvay, now Abbott Laboratories', Creon and Eurand’s Zenpep have publicly announced that they have secured US marketing authority under the new much stricter rules, meaning that they could ultimately be the winners in this market that some believe could eventually hit $1bn.

The old ways

Currently, the majority of PEPs now on the market (see table below) were in use before the Federal Food, Drug and Cosmetic Act was passed in 1938, meaning that they have never had to seek formal approval, or been subject to rigorous checks over their efficacy, safety or different dosing strengths.

What particularly worried the regulator was the practice of overfilling. Because of their nature PEPs, which are derived from pig enzymes, are unstable and so to compensate for the enzymes degrading over time manufacturers would overfill treatment doses. The result was patients receiving varying doses of the drug and therefore varying therapeutic benefit.

The laissez-faire stance by the regulator over these old products has changed and in 2006 it stated that unapproved PEPs would have to seek marketing approval and those not approved by April 28, 2010 removed from the market.

Giving up the ghost

The now much stricter rules stipulate that manufacturers should ensure the dose stated on the label is the actual dose, as well as having a process whereby viral agents can be removed or inactivated and full chemical characterisation of the enzyme available for inspection. Therefore many in the market, who had been making generic products, appear to have given up on the quest for approval.

UCB used to market three products including Cotazym, which was the only FDA approved product before the regulator announced it would be tightening up the rules in 2006. The Belgian company has narrowed its focus down to CNS and immunology products, has stopped commercialising Cotazyme and makes no mention of any of its other PEP products on its website.

Altus, which had one of the more novel approaches to the disorder with its non pig-derived product, Trizytek, abandoned development of the drug following less than impressive phase III results in January 2009, in order to focus on a growth hormone.

Narrowing the field

What is not clear is Axcan Pharma’s progress with its product Ultrase. As a private company the Quebec-based group does not have to disclose any progress that it has made with the regulator. Some are expecting that Ultrase might yet be a third approved product in the space come the April deadline.

For Eurand, which manufactures the ingredients in the Axcan product, it would be better to just have Zenpep and Creon on the market. However, if Ultrase does make the cut, Eurand will at least have the consolation of receiving manufacturing revenues and 25-30% royalties on Ultrase sales.

Increased opportunity

James Molloy, healthcare analyst with Caris & Company, believes that the market for PEP products in the US is currently worth about $300m. But he argues that the clear-out of the market could increase the price that the remaining branded companies can charge, once the low-cost unbranded products go.

“It could double to $600m by 2012. There is no reason why the likes of Abbott and Eurand will not be able to charge twice as much as they are now.”

Although Abbott is not focused on such niche products, the wider market opportunity could mean that the group steps up its efforts in the PEP market.

However, in the short term the sales of the two approved products on the market could fall as the generic manufacturers try to offload their supplies of PEPs even more cheaply ahead of the April 28 deadline. If doctors do decide to stockpile these drugs then sales of the winners from the FDA shake out could be dented for some time.

But the FDA is expected to take rapid action in clearing any unapproved product from the shelves of wholesalers, a move that would be welcomed by the likes of Eurand and Abbott who could be the primary market winners come April 28.

Pancreatic Enzyme Products
Annual Sales WW - ($m)
Phase Product Company Proprietary Level 2008 2009 2010 2012 2014
Marketed Creon Abbott Laboratories Generic - Branded (aNDA) - - 296 435 360
Zenpep Eurand NDA + Proprietary Drug Delivery - 13 82 163 212
Ultrase Axcan Pharma/Eurand NDA (Patented Compound) 59 73 82 100 117
Pancrease Johnson & Johnson Unclassified - - - - -
Cotazym UCB Unclassified - - - - -
Kutrase UCB Unclassified - - - - -
Ku-Zyme UCB Unclassified - - - - -
Viokase Pfizer/Axcan Pharma Generic - Branded (aNDA) 15 - - - -
Panzytrat Axcan Pharma Generic - Branded (aNDA) 17 - - - -
Seven E-P Kaken Pharmaceutical Unclassified - - - - -
Plaretase KV Pharmaceutical Generic - Branded (aNDA) - - - - -
Pangestyme KV Pharmaceutical Generic - Branded (aNDA) - - - - -
Pankreoflat Faes Farma Generic - Branded (aNDA) - - - - -
Pancrecarb Digestive Care NDA (Patented Compound) - - - - -
Phase III Liprotamase Alnara Pharmaceuticals NDA + Proprietary Drug Delivery - - - - -
Phase II Exinalda AstraZeneca/Swedish Orphan Biovitrum NME (Patented Compound) - - - - -
Kiobrina Swedish Orphan Biovitrum NME (Patented Compound) - - - - -

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