Eurand's formulations stack up at the FDA

By Pete Mansell

- Last updated on GMT

Drug delivery specialist Eurand could see a marked increase in
revenue flow this year, both from co-development products
incorporating the company's formulation technologies and a
proprietary treatment addressing the estimated $720m worldwide
market for exocrine pancreatic insufficiency (EPI).

The company and its partners now have three approval dossiers lodged with the US Food and Administration (FDA), which Eurand is hoping will lead to three product launches later this year. The company also has more than 10 other product candidates at various stages of development. One of the development partners, GlaxoSmithKline (GSK), filed a new drug application (NDA) for EUR-1048, a rapid-dissolve version of an undisclosed GSK compound formulated by Eurand with its Microcap taste-masking and AdvaTab orally disintegrating tablet (ODT) technology, during the fourth quarter of last year. Assuming approval, GSK expects to launch the product late in 2008. Under its agreement with GSK, Eurand will supply EUR-1048 exclusively to the UK company, receiving manufacturing revenues and royalties on future sales. Including payments already made for achieving development milestones, Eurand stands to receive up to $42m in total under its partnership with GSK. The Microcaps system masks unpleasant tastes or odours by encapsulating each particle of the drug substance in a continuous membrane that forms an inert barrier between the drug and the taste buds. Meanwhile, the AdvaTab dosing technology promises not only rapid dissolution (around 30 seconds in the mouth without water) but advantages over conventional manufacturing processes by compressing the tablets with an external lubrication system. This generates hard, durable tablets that do not require high compression forces during production and do not repel liquids when ingested, Eurand says. Another GSK compound, but one that is now genericised, forms the basis of EUR-1025, a proprietary, once-daily oral formulation of ondansetron hydrochloride currently under development by Eurand using its Diffucaps multiparticulate system. Ondansetron is marketed by GSK under the Zofran brand for the treatment and prevention of chemotherapy-induced nausea and vomiting. Current formulations of the drug are administered two to four times a day, and Eurand believes its Diffucaps formulation could offer significant advantages for patients. In late February, the company reported positive results from a pilot pharmacokinetic study comparing the once-daily EUR-1025 formulation with an 8mg tablet of Zofran dosed twice a day. "The study achieved its goal of producing a formulation with a similar pharmacokinetic profile which was bioequivalent when normalised for dose,​" Eurand reported. The company says it expects to discuss further development of EUR-1025 with the FDA shortly and to start any required pivotal studies with the once-daily formulation before the end of the year. Reported worldwide sales of ondansetron for the 12 months to 30 September 2007 were around $1.6bn, roughly $1bn of which were for the oral dosage form. The Diffucaps system is designed to provide optimal release profiles for either single compounds or drug combinations. These are created by layering the active drug onto a neutral core (such as cellulose spheres), then applying one or more rate-controlling functional membranes. The resulting Diffucaps beads are incorporated into a capsule to create the final dosage form. The beads are only around 1mm in diameter and high levels of control can be achieved by combining beads with varying drug-release profiles (e.g., sustained-release, pulsatile-release, immediate-release) in a single capsule, Eurand says. Alternatively, Diffucaps beads of different drugs can be combined to form convenient single-dose units for combination therapies. The system is currently in use with products marketed in the US, the European Union and Japan, such as a timed and sustained-release dosage form of the beta-blocker propranolol developed for Reliant Pharmaceuticals and launched in the US as Innopran XL. Eurand has also developed for Reliant EUR-1000, a Diffucaps formulation designed as an AB-rated generic equivalent (i.e., one that can be substituted by a pharmacist for the branded version without physician approval) of Inderal LA, which is a long-acting version of propanolol indicated for the treatment of hypertension and migraines. An abbreviated new drug application (ANDA) has been filed for EUR-1000 and a launch is expected this year. Also employing the Diffucaps technology is EUR-1002, a once-daily formulation of the skeletal muscle relaxant cyclobenzaprine hydrochloride that was launched in the US as Amrix by Cephalon in November 2007. Indicated for the relief of muscle spasm associated with acute, painful musculoskeletal conditions, Amrix is the only FDA-approved once-daily formulation of cyclobenzaprine on the US market, Cephalon notes. Eurand's chief executive officer Gearoid Faherty, described Amrix as "a perfect example of the power of Eurand's technology and development capabilities​". Most currently marketed skeletal muscle relaxants are dosed several times a day, he noted. They also cause varying degrees of somnolence, whereas Amrix was associated in clinical trials with a lower incidence of somnolence than immediate-release cyclobenzaprine. As with its MicroCaps/AdvaTab partnership with GSK, Eurand is the exclusive supplier of Amrix to Cephalon and receives both manufacturing revenues and royalties on product sales. As Faherty pointed out in a conference call for Eurand's fourth-quarter and annual results, Cephalon reported sales of $8.4m for Amrix in Q4 2007. Eurand's partner is using a specialist central nervous system sales team to detail the product and believes it can reach 40-50 million of the top-tier muscle relaxant prescribers in the US, Faherty added. The third product that Eurand hopes to see launched in the US this year is the company's lead development candidate, Zentase. This is a porcine-derived pancreatic enzyme replacement therapy for EPI, which is associated with cystic fibrosis, chronic pancreatitis and other conditions. EPI results in poor digestion and reduced absorption of nutrients which, left untreated, can lead to malnutrition, impaired growth, weakened immune response and shortened life expectancy. According to Eurand, Zentase is a highly stable formulation that includes eight key enzymes, as well as a number of co-enzymes and co-factors, and is biologically similar to the endogenous human pancreatic secretions needed for proper human digestion. A rolling NDA submission for Zentase (EUR-1008) was completed last December, and last month the FDA accepted the filing and granted the product the priority review requested by Eurand. Priority review status typically means a six-month assessment for the NDA as opposed to the FDA's standard 10-month review time, Faherty pointed out. Eurand hopes to launch the product in the third quarter of 2008. In this respect it can draw on the resources of SourceCF, a speciality pharmaceutical company focused on cystic fibrosis (CF) and acquired by Eurand last December for $6.6 million in cash. As well as a product portfolio that includes a range of vitamins for CF patients and the eFlow electronic nebuliser for drug delivery, SourceCF brings on board 15 experienced sales and support professionals dedicated to the CF community. According to Flaherty, the acquisition has "greatly expanded​" Eurand's product range and credibility with CF physicians while accelerating the "build-out​" of the company's sales and marketing infrastructure for the Zentase launch. Eurand is looking to license out Zentase for European markets and Japan. Based on current discussions, it expects to sign licensing deals in Europe by the end of the first half and in Japan later this year. There are also further co-licensing agreements in the bag. Eurand signed six of these in 2007, including its deal with Cephalon for Amrix. Flaherty said the others were with a number of large and medium-sized pharmaceutical and biotechnology companies, covering a range of geographies and therapeutic areas. Moreover, they "reinforce our position as one of the leading companies in this space today​". Eurand will be glad of the extra revenues from these sources. While the company raised $112m before expenses in an initial public offering last May, it ended the year with an operating loss of €4.1m ($6m) compared with a €3.8m operating profit for 2006. Revenues for 2007 were €84.8m, 2.4 per cent higher than in the previous year.

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