FDA Briefing Package (Gemifloxacin) Anti-Infective Drugs Advisory Committee (March 4, 2003) New Drug Application (NDA) 21-158 Factive (gemifloxacin mesylate)

WALTHAM, Mass.--(BUSINESS WIRE)--Sept. 9, 2004--Oscient Pharmaceuticals Corporation (Nasdaq: OSCI) has launched once-daily FACTIVE(R) (gemifloxacin mesylate) tablets (320 mg), a potent new oral antibiotic approved by the United States Food and Drug Administration (FDA) for the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB) and mild to moderate community-acquired pneumonia (CAP). Together, these conditions afflict more than 17 million individuals in the United States each year, resulting in significant illness, economic expense and, in some cases, death.

FACTIVE tablets, part of the fluoroquinolone class of antibiotics, were the first antibiotics approved for the treatment of multi-drug resistant Streptococcus pneumoniae (MDRSP) and have the shortest course of therapy for this indication (seven days). FACTIVE tablets are the most active antibiotics against S. pneumoniae available to physicians today based on laboratory testing (using minimum inhibitory concentrations, or MICs). FACTIVE tablets cover a broad spectrum of strains that are resistant to other antibiotic classes and attack bacteria at two sites (dual targeting). With resistance rates to older antibiotic classes ranging from 25 to 30 percent and continuing to increase, FACTIVE tablets offer physicians an important new treatment option.

"FACTIVE tablets are an important option for first-line therapy for ABECB and CAP, especially for at-risk patients, people who have received antibiotics within the past three months or those who have significant underlying medical conditions such as COPD, diabetes, renal failure or malignancies," said Thomas File, M.D., Professor of Internal Medicine, Northwestern Ohio Universities College of Medicine and a lead FACTIVE clinical investigator. "As such, the Infectious Diseases Society of America's outpatient CAP treatment guidelines recommended use of fluoroquinolones, such as FACTIVE tablets, as appropriate first-line therapeutic options in these populations. FACTIVE tablets are the most active of the respiratory fluoroquinolones against S. pneumoniae in the laboratory setting."

Once-daily FACTIVE tablets offer short-course dosing (five days for ABECB and seven days for CAP) with no dosing adjustment requirements in the elderly, individuals with liver impairment or individuals with mild-to-moderate renal impairment.

"Oscient's once-daily FACTIVE tablets are a powerful, first-line, short-course therapy that will provide physicians and patients an important new treatment option while playing a role in reducing the medical and economic burden of these two conditions," said Steven M. Rauscher, President and Chief Executive Officer of Oscient Pharmaceuticals. "The launch of FACTIVE tablets is a major milestone for the medical community and for Oscient."

Oscient continues to develop FACTIVE tablets for the treatment of respiratory tract infections. Clinical trials for the treatment of acute bacterial sinusitis (ABS) are complete and a regulatory submission for that indication is planned for next year, pending the outcome of planning discussions with the FDA. In addition, Oscient is conducting a Phase III trial of FACTIVE tablets for the potential treatment of CAP in five days and is developing a FACTIVE intravenous formulation for the potential treatment of patients hospitalized with severe CAP. FACTIVE has not been approved for either severe CAP, five-day CAP or ABS at this time.

Clinical Studies of FACTIVE Tablets

The safety and efficacy of FACTIVE tablets were established through a robust clinical development program involving 6,775 patients. In these studies, FACTIVE tablets demonstrated excellent clinical response rates at test-of-cure visit for CAP and ABECB as good as comparators including clarithromycin, levofloxacin, amoxicillin/clavulanate, ceftriaxone and oral cefuroxime.

Two studies published in the August issue of Respiratory Medicine further supported the safety and efficacy of FACTIVE tablets. In the first study involving 324 patients with suspected pneumococcal CAP, once-daily FACTIVE tablets (320 mg) for seven days were found to be as clinically effective as ten days of high-dose amoxicillin/clavulanate (1g/125 mg) taken three times daily. In the second study involving 360 patients with ABECB, once-daily FACTIVE tablets (320 mg) for five days were clinically equivalent to levofloxacin (500mg) taken once-daily for seven days. The clinical success rates at long-term follow-up in this study were 80.8% for FACTIVE tablets and 70.8% for levofloxacin in the intent-to-treat population, a statistically significant difference. The study also showed that FACTIVE tablets and levofloxacin were safe and well-tolerated, although the withdrawal rate due to adverse events was lower with FACTIVE tablets (2.2%) than with levofloxacin (5.6%).

Important Safety Information about FACTIVE Tablets

The most common (more than 2% incidence) side effects reported in FACTIVE clinical trials were diarrhea (3.6%), rash (2.8%) and nausea (2.7%). In clinical trials, rash was reported in 2.8% of patients receiving gemifloxacin and was more commonly observed in patients less than 40 years of age, especially females. The incidence of rash increases with treatment longer than the maximum-labeled duration of 7 days. In clinical trials, the discontinuation rate due to related adverse events was similar for FACTIVE tablets and comparators (2.2% versus 2.1%, respectively).

Gemifloxacin is contraindicated in patients with a history of hypersensitivity to gemifloxacin, fluoroquinolone antibiotic agents, or any of the product components.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of FACTIVE tablets and other antibacterial drugs, FACTIVE tablets should be used only to treat infections that are proven or strongly suspected to be caused by bacteria.

Patients receiving marketed fluoroquinolones have reported serious and occasionally fatal hypersensitivity and/or anaphylactic reactions, peripheral neuropathy, and tendon ruptures. These adverse events have not been reported by patients taking gemifloxacin. However, gemifloxacin should be discontinued immediately at the first sign of any of these events.

Gemifloxacin may prolong the QT interval in some patients. Gemifloxacin should be avoided in patients with a history of prolongation of the QTc interval, patients with uncorrected electrolyte disorders (hypokalemia or hypomagnesemia), and patients receiving Class IA or Class III antiarrhythmic agents.

In clinical studies with gemifloxacin, CNS effects have been reported infrequently. As with other fluoroquinolones, gemifloxacin should be used with caution in patients with known or suspected CNS diseases. If CNS reactions occur, gemifloxacin should be discontinued and appropriate measure instituted.

No significant drug-drug interactions were seen with theophylline, digoxin, oral contraceptives, cimetidine, omeprazole, and warfarin, although patients receiving a fluoroquinolone concomitantly with warfarin should be monitored closely. Drug-drug interactions include probenicid, sucralfate, antacids containing aluminum or magnesium, iron, multivitamins containing metal cations, and didanosine.

The safety and effectiveness of gemifloxacin in children, adolescents (less than 18 years of age), pregnant women, and lactating women have not been established. For complete safety and efficacy information, please see the full prescribing information available at www.FACTIVE.com.

About Oscient Pharmaceuticals

Oscient Pharmaceuticals Corporation is a biopharmaceutical company committed to the clinical development and commercialization of novel therapeutics to address unmet medical needs. The Company is marketing FACTIVE(R) (gemifloxacin mesylate) tablets, approved by the FDA for the treatment of acute bacterial exacerbations of chronic bronchitis and community-acquired pneumonia of mild to moderate severity. In addition to the oral tablet form, Oscient Pharmaceuticals is developing a FACTIVE intravenous formulation for use in hospitalized patients.

The Company has a novel antibiotic candidate, Ramoplanin, in advanced clinical development for the treatment of Clostridium difficile-associated diarrhea (CDAD). The Company's preclinical program includes an oral peptide deformylase (PDF) inhibitor series, under preclinical development for community-based respiratory tract infections.