BioAlliance Pharma Announces Publication Demonstrating Potential of Miconazole Lauriad Bioadhesive Buccal Tablets to Provide Improved Antifungal Drug Exposure in the Oral Cavity.

PARIS -- Once Daily Application May Improve Patient Compliance and Avoid Drug Interactions and Adverse Effects in Treatment of Oropharyngeal Candidiasis 

BioAlliance Pharma, a biopharmaceutical company focused on the field of drug resistance, today announced that a research team, including the company, reported results demonstrating the potential superiority of a new formulation of miconazole administered as a bioadhesive extended release buccal tablet compared to the same drug applied in a topical gel for treatment of oropharyngeal candidiasis, an oral fungus commonly known as "thrush".

The research team came from the Biopharmaceutics department, Faculty of Pharmacy, University of Clermont-Ferrand, France, and BioAlliance Pharma. The study was reported in the British Journal of Clinical Pharmacology (Vol. 58, No. 4: 345-351, 2004).

"This study of our once a day topical formulation of miconazole in the form of a an extended release bioadhesive buccal tablet played a key role in our decision to proceed with further clinical development of this first product utilizing the Lauriad drug delivery platform," said Dominique Costantini, M.D., president and CEO of BioAlliance Pharma. "The two completed Phase 3 trials in the EU and the planned Phase 3 trial in the US are designed to demonstrate the superiority of this approach in the treatment of oropharyngeal candidiasis commonly found in immune compromised patients, including HIV and cancer patients, diabetics and the elderly."

While current treatment guidelines for oropharyngeal candidiasis call for use of topical or localized therapies whenever possible, currently available gels, lozenges and mouthwashes have been generally unsuccessful in treating this infection. This is due to their multiple daily applications, unpleasant taste and transient drug concentration in the oral cavity. The lack of effective local treatments has lead to preferential use of systemic anti-fungal agents.

In order to provide a first-line alternative to treatment using systemic therapies, the current study was designed to demonstrate the potential of a once daily application of a buccal tablet formulated to provide an extended release of miconazole. Miconazole is a well-known antifungal with broad-spectrum activity against various species of Candida. Such an approach would eliminate the problems of patient compliance and tolerance associated with other topical treatments. At the same time, it would increase the likelihood of therapeutic success through prolonged exposure to miconazole in the oral cavity at a level sufficient to effectively eradicate the Candida and avoid the drug-drug interactions and development of microbiological resistance frequently associated with systemic therapy.

The study was conducted using a proprietary bioadhesive buccal tablet (Lauriad(R)) placed on the cuspid fossa beneath the upper lip. This placement allows the tablet to adhere to the buccal mucosa for an extended period while releasing the antifungal agent. A natural polymer, extensively used in the food industry, with good tolerance and appropriate adhesive properties was used to formulate the drug. The tablet adheres to the gum and then absorbs water, which triggers sustained release of miconazole and tablet erosion. Once the tablet is in place, patients can eat, drink and carry on normal daily activities while the tablet dissolves, slowly or gradually releasing the drug.

In the study, plasma and salivary measurements of miconazole were assessed in 18 healthy subjects over a 24-hour period. In all subjects, the single administration of a 50 mg tablet of miconazole Lauriad(R) gave higher and more prolonged salivary concentrations of the drug than did the gel. A 100 mg tablet was also tested in the study but the 50 mg tablet demonstrated better tolerance and acceptability, primarily due to its smaller size. The mean duration of tablet adhesion was 15 hours.

Mean salivary concentration was consistently 18.9 times greater when compared to a commonly used miconazole gel administered 3 times over a 12-hour period for a total dose of 375 mg -- 7.5 times higher than the Lauriad(R) 50 mg tablet. The mean time that salivary concentrations of miconazole were above the minimal inhibitory concentration level needed to treat the infection was 7 hours for the tablet compared with 1.5 hours for the oral gel.

Plasma miconazole concentrations were generally below the limit of detection, confirming a very low absorption through the buccal mucosa or the gastrointestinal tract after swallowing saliva.

"Data from the study strongly support the further development of miconazole Lauriad(R) 50 mg bioadhesive buccal tablets as an extended release formulation leading to improved antifungal exposure in the oral cavity," said Professor Jean-Marc Aiache, Emeritus Professor, Biopharmaceutics Department, Faculty of Pharmacy, University of Clermont-Ferrand, France, and inventor of the Lauriad(R) technology.

"A single daily application with a low dose of miconazole could improve patient compliance and might also diminish drug-drug interaction, supporting the safety profile of the miconazole Lauriad(R) tablet in the Phase III studies," said Professor Jean-Michel Cardot, Department Head, Biopharmaceutics Department, Faculty of Pharmacy, University of Clermont-Ferrand, France, an investigator on the study.

About BioAlliance Pharma

BioAlliance Pharma is a privately held biopharmaceutical company focused on the development and commercialization of innovative therapeutics and predictive assays in the field of drug resistance, targeting cancer and infectious diseases, including in particular HIV. The company has a balanced portfolio of products and proprietary technologies in various stages of development, from preclinical research to a product currently on the market. To supply its extensive pipeline of products, BioAlliance maintains a unique network of alliances with leading academic investigators from French research institutions, including the Centre National de la Recherche Scientifique (CNRS), the Institut National de la Sante et de la Recherche Medicale (INSERM) and the Institut Pasteur, among others.

The company's lead product within its adhesive technology program, the miconazole Lauriad(R) 50 mg Bioadhesive Buccal Tablet, is being investigated in two recently completed Phase III trials in Europe for treatment of oropharyngeal candidiasis in cancer and HIV patients. An IND to conduct a Phase III trial in the US is on track for filing early next year. A second product utilizing the Lauriad(R) drug delivery platform, acyclovir Lauriad(R) for treatment of oral herpes, is scheduled to enter the clinic by early 2005. A Phase I/II trial in hepatocellular carcinoma utilizing the company's doxorubicin Transdrug(TM) delivery technology is ongoing in Europe.

For additional company background, please visit the BioAlliance Pharma web sites at: www.BioAlliancepharma.com and www.viralliance.com.