Cystic Fibrosis: Eurand Launches Zenpep, Joins Breed Of Remade Pancreatic Enzyme Products

Rival's claim that porcine-derived product trials took only treatment responders is "baloney," says Eurand lead investigator.

Specialty pharma Eurand has officially launched its pancreatic enzyme product Zenpep , one of a new breed of porcine-derived products that meet tighter FDA standards required by 2010.

Pancreatic enzyme products, also called pancreatic enzyme replacement therapies, treat maldigestion, malabsorption and malnutrition caused by exocrine pancreatic insufficiency, which afflicts about 90 percent of cystic fibrosis patients. The condition is also common in patients with chronic pancreatitis, pancreatic tumors and pancreatectomy.

Manufacturers of PEPs have been making over their products to conform with new FDA regulations that take effect next year. Zenpep is brand new, though Eurand had extensive experience in the market, having previously developed a pancrealipase product marketed as Ultrase by Axcan.

Four dosages of Zenpep (pancrelipase) delayed-release capsules are now available (5,000, 10,000, 15,000 and 20,000 units of lipase) to meet the needs of patients at all ages.

"We believe it's very important to offer patients control at the lowest effective dose," said Michael Walters, executive vice president of sales & marketing at Philadelphia, Penn.-based Eurand.

The product has been tested in children as young as one year, the company points out.

Eurand rolled out Zenpep throughout November in the U.S. and officially launched the product on Nov. 30. In cystic fibrosis, the company has 16 of its own sales people targeting a range of specialists at120 accredited centers. For the other indications, Eurand struck a sales and marketing deal with Innovex, a Quintiles company. According to the agreement, about 50 sales professionals will call on key gastroenterologists, internal medicine specialists, family practice physicians, and oncologists. Initially, samples will be made freely available for the non-CF indications.

The global market for PEPs was worth over $1 billion in 2008, and Eurand estimates about half of this figure derives from cystic fibrosis.

Coming up to regulatory snuff

Approved Aug. 27 for the treatment of EPI due to cystic fibrosis or other conditions, Zenpep was developed specifically to meet new FDA standards for PEPs.

Introduced before the Food, Drug and Cosmetic Act was enacted in 1938, PEPs historically have not been regulated and approved by the FDA and quality has been questionable. Short shelf life has been problematic, resulting in unpredictable doses, and, in the past, manufacturers have over-filled their products to compensate for product degradation. Also, most PEPs are made from the pancreatic tissue of swine and products made from animals carry the theoretical risk of transmission of viral disease to patients.

Consequently, FDA called for better control of these products and drafted new quality standards in 2004 (Also see "Pancreatic Insufficiency Drug Makers Given NDA Approval Deadline Of 2008" - Pink Sheet, 27 Apr, 2004.). All manufacturers of EPI products were required to file NDAs and receive marketing approvals by April 2010.

"The originals were not required to undergo safety and efficacy testing. In 2009, FDA would never allow products to come to the market like that," said James Heubi, lead investigator on the Zenpep trials. "I think this brings products in line with modern expectations for efficacy and safety."

Complying with the new regulations is expensive and, as a result, generic manufacturers have all exited the market, creating sales opportunities for makers of branded drugs who are willing to make the investment in bringing treatments up-to-date.

In May, Solvay became the first to receive FDA approval for its new version of Creon , which was launched commercially in July ( (Also see "New Drug Approvals & Regulatory Updates, In Brief" - Pink Sheet, 4 May, 2009.) May 4, 2009). With sales of $300 million in 2008, Creon is one of Solvay's biggest revenue-generators. Two others are now pending FDA review: Axcan's Ultrase and Digestive Care's Pancrecarb . Alnara Pharmaceuticals plans to file an NDA for its porcine-free liprotamase in the first quarter of 2010 (Also see "This Little Pig-Free Product Goes To Market? Alnara's High Hopes For A PERT" - Pink Sheet, 19 Oct, 2009.).

Cystic fibrosis focus on young kids

Eurand's application was supported by two Phase III multicenter clinical trials - one in older children, adolescents and adults, and the other in young children aged 1 through 6.

Developing products for young children is becoming more important with the rise of mandatory screening of newborns for cystic fibrosis in states across the country. Among other differentiating factors, Eurand is planning to play up the fact that its product has been tested in very young children and is available in four different doses to suit patients at a variety of ages.

Another potential product advantage came to light in clinical testing. The current standard of PEP care involves taking 15 or more large capsules a day with meals, which is a large pill burden, especially for children. On top of that, cystic fibrosis patients typically also take nutritional supplements and proton pump inhibitors to improve fat absorption. In most EPI trials, patients are taking PEPs plus PPIs and/or hydrogen sulfides, also called H2s.

Trial design in the Zenpep studies specifically excluded use of PPIs or H2s and yet the product was just as effective. Cystic fibrosis patients are typically on a "gazillion pills," and the results suggest Zenpep makes it possible to reduce pill burden, said Heubi, who is director of the Clinical Research Center at Cincinati Children's Hospital Medical Center.

Efficacy of PEPs is based on "coefficient of fat absorption" (CFA) testing, which is measured in stool samples. CFA was statistically higher with Zenpep treatment at 88.3 percent versus 62.8 percent for placebo in the study of older children and adults.

Completing stool collection in very young kids is nearly impossible, so in the second study investigators evaluated symptom control as a gauge of efficacy.

Next year, Zenpep and other porcine-derived products could face competition from a non-porcine product developed by Cambridge, Mass.-based Alnara using recombinant technology. The rival recombinant product-- Tryzytek (liprotamase) -- has proven effective with only five pills a day.

CFA results for liprotamase disappointed investors because they were not as robust as for the porcine-based treatments. But Alnara has argued that the measure is crude and not a reliable indicator of clinical outcomes. Furthermore, the company has argued that trials involving porcine products were marketing studies that accepted participants only if they showed a treatment response, whereas its studies included "all-comers," that is responders and non-responders.

Asked to comment on that claim, Heubi offered a one-word response.

"Baloney," he said.

Zenpep trial investigators did not select patients based on treatment response and CFA testing is well-accepted, he explained. Less robust effects on CFA could be related to the fact that the non-porcine product does not include a factor called co-lipase that potentiates the effect of lipase.

"This likely explains the inferior performance of the yeast/bacterially derived enzymes," he explained.

- Emily Hayes ( [email protected] )