Media Contact:
Joe Feeks, PR Works, 243 Edgartown Road, PMB 239, PO Box 9000, Edgartown, MA02539, USA
TEL +1 508 627 6949 FAX +1 928 569 2491 (efax) EMAIL jfeeks@prworks.net
European Commission Lifts Marketing Suspension On New-Generation Pleuromutilin; Unique Swine Antibiotic Backed by Worldwide Pharmacovigilance Programme
Novartis Animal Health, Inc., announced today that it will relaunch its swine antibiotic Econor® (valnemulin) in the EU following a decision by the European Commission (EC) to lift the 19-month marketing suspension on the unique, new-generation pleuromutilin.
The EC ruling was made after the unanimous recommendation of the Committee of Veterinary Medicinal Products (CVMP) to reinstate the product's Marketing Authorisation with an amendment to the warning on the product's label.
"We are most grateful to the European Commission, CVMP and EMEA for the time they invested to review the facts and make an objective risk-benefit assessment of Econor," says Dr. Bernhard Putz, head of the company's Farm Animal Business Unit.
"While challenging at times, this exhaustive and thorough process has helped to validate the safety of Econor, further strengthen user confidence in the product and, in our view, make the unique antibiotic even more valuable to the worldwide pork industry."
'New territory'
Reflecting on the past four years, Putz notes that Econor has achieved several regulatory firsts during its brief history. After a successful launch in Vietnam, Malaysia and Peru in 1998, Econor came to Europe the following year and became the first antibiotic feed premix to be approved through the centralized registration procedure in all member states of the EU.
In 2000, following a series of suspected adverse drug reactions, principally in Scandinavia, Econor had the dubious honour of becoming the first food animal product to have its Marketing Authorisation suspended by the European Commission. With the recent reversal of this decision, Econor now becomes the first animal health product to have its license reinstated following an intensive re-evaluation process.
(Note to editors: See editorial backgrounder, "History of Econor in the EU" for more information about the marketing suspension.)
"The relicensing of Econor has been new territory for everyone involved," Putz says. "The relaunch of the product is a good example of what can happen when everyone in the industry - pharmaceutical companies, regulatory authorities, veterinarians, nutritionists, epidemiologists -pools their expertise, objectively evaluates the facts and ultimately does what is best for the EU pig industry. We are pleased that sound science had the final word."
Reduced withdrawal time
In addition to regaining marketing authorization for Econor, Novartis Animal Health said it had also received approval of a new, more flexible 1-day withdrawal time for its popular 10% and 50% premix formulations. The previous withdrawal period was 4 days. Econor's 0.5% and 1% formulations already had the 1-day withdrawal.
"The new 1-day withdrawal period on the10% and 50% formulations gives producers added marketing flexibility, particularly when treating diseases such as swine dysentery or pneumonia late in the fattening phase," says Colin Meyers, international brand manager for Econor.
According to Meyers, Novartis Animal Health will resume marketing Econor immediately in most EU markets and begin shipping the10% formulation by mid-June. The other formulations of Econor are expected to become available later this summer.
For food animals only
Econor is a semi-synthetic antibiotic that interferes with bacterial protein synthesis at the ribosomal level. Valnemulin, the active ingredient in Econor, inhibits the creation of peptide chains by preventing the addition of amino acids needed for protein production. Without these basic building blocks, the target organisms are unable to grow and reproduce.
"Econor is unique in that it was developed specifically for use in food animals and no pleuromutilin antibiotics are used in human medicine," says Dr. Ulrich Klein, a professional services veterinarian for the company. "This is a tremendous benefit with the growing concern for cross-resistance and transfer of resistance to humans."
From a production standpoint, Klein adds, Econor has been shown to be the most active product for preventing and treating swine dysentery. Field trials have also demonstrated good efficacy against tylosin- and lincomycin-resistant strains of Brachyspira hyodysenteriae, the causative organism of swine dysentery. Research has also shown activity against spirochaetal colitis and ileitis, and Novartis is actively pursuing label claims for these increasingly significant conditions.
The development of Econor also gave the world's pig industry a new dimension in antibiotic activity for preventing and treating enzootic pneumonia.
Studies throughout the EU, Latin America and the Pacific Rim show that diseased pigs treated with Econor have significantly better daily gains and feed conversion than untreated controls.
Isolated reactions
Despite its early success throughout the EU, including Scandinavia, Econor hit a bump in the road in October 2000 when the European Commission suspended the product's license following a series of adverse drug reactions in four EU countries.
Of the 36 cases reported, 34 of them - or more than 94% - occurred in Denmark and Sweden. One was reported in Finland and another in Ireland. Still, overall incidence of ADRs in the affected countries ranged from 0.03% to 1.76% of all pigs treated. Mortality rate in affected herds ranged from 0.7% to 1.2%.
"The ADRs in Denmark and Sweden were really puzzling," Klein says. "With the exception of two isolated cases, we had not seen these types of reactions - fever, lack of coordination, depression, oedema, to name a few - anywhere else in the EU, nor had any been reported in Eastern Europe, Latin America or the Pacific Rim."
"Furthermore, while the ADRs in the affected countries seemed to be associated in some way with the use of Econor, the product alone could not have accounted for all the observed effects we were seeing in Scandinavia."
Initially, Klein says, veterinarians, epidemiologists and pathologists thought the ADRs might be linked to nutritional programmes or interactions with other feed ingredients unique to these countries. Since then, however, investigators have trained their sights on the breeding programmes used in Denmark and Sweden and, more specifically, a possible deficiency of the enzyme CYP2A P450. This deficiency can slow the metabolic processes of swine and, in turn, could make pigs more susceptible to ADRs.
(Note to editors: See editorial backgrounders, "One of a Kind - Unique Breeding Schemes in Denmark and Sweden May Be Factor in Mystery ADRs" and "Novartis Completes Extensive Investigation Of Mysterious Adverse Drug Reactions" for more information.)
"Scientists are still conducting studies to identify the exact cause of the problem in Scandinavia," Klein says. "Meanwhile, statistics and circumstantial evidence strongly suggest that ADRs seen in Denmark and Sweden are restricted to pigs bred for those markets. We do not expect this phenomenon to spill over to other markets, unless the pigs being raised are of Scandinavian origin."
Modified label
To make sure veterinarians and producers are aware of the risks associated with these specific breeding lines, Novartis has reintroduced Econor with a new label advising "extreme care" with the product's use in "pigs of Scandinavian origin," especially Danish and Swedish Landrace breeds and their crossbreeds.
The company has also re-emphasised the duties of pharmacovigilance managers and their deputies in each market to closely monitor product performance - not just for Econor, but for Tiamutin® (tiamulin) and the company's other food animal health products.
"ADRs are rarely seen when animal health products are used according to label directions, but we want to be ready for them when and if they occur," Putz says. "Besides designating pharmacovigilance managers for all subsidiaries, we have trained our sales, professional services and regulatory people to respond quickly to suspected ADRs, all of which will be reported to the regulatory authorities. As before, we are committed to maintaining a clearly defined, open-book policy designed to keep the industry informed of ADRs and to ensure a quick response."
For more information about Econor, contact the company at Novartis Animal Health, Inc., WRO 1032.3.41/AH 6.4, CH-4002, Basel, Switzerland. Tel: +41-61-697-7851.
