West Coast Editor

Advancis Pharmaceutical Corp. said it has the go-ahead from the FDA to start a Phase III trial of Amoxicillin Pulsys, a tablet formulation of the popular antibiotic that provides longer exposure, lower dosing and a shorter course of therapy.

The trial will begin next month, with results expected between April and June 2005, said Edward Rudnic, chairman, president and CEO of Germantown, Md.-based Advancis.

"For a Phase III trial, it's relatively quick," he said.

The company's stock (NASDAQ:AVNC) closed Friday at $8.30, up 20 cents.

Advancis is moving forward with a clinical program designed to support approval of Amoxicillin Pulsys for acute pharyngitis/tonsillitis in adults and adolescents due to Group A streptococcal infections.

The trial is a two-arm, 500-patient, double-blind, non-inferiority Phase III study comparing Amoxicillin Pulsys for pharyngitis in a once-daily, 775-mg tablet for seven days to the FDA standard comparator therapy of 250-mg of penicillin dosed four times daily, for 10 days.

Primary endpoint for the study will be bacterial eradication, as measured by throat swabs before and after treatment. The trial will be conducted mainly in individual or group physicians' offices specializing in family practice, pediatric or internal medicine. Through a contract research organization, Advancis has accepted 60 sites in 22 states across the U.S.

An investigators' meeting is slated for Oct. 1, and Advancis expects to begin dosing patients later that month, with a new drug application filing likely in the second half of 2005.

The Pulsys technology amounts to a combination of polymers and osmotic ingredients that allows for "rapid staccato bursts of antibiotic, as opposed to normal waves," with the first burst being released in the stomach and later pulses at "very definite, reproducible and localized areas" in the gastrointestinal tract, Rudnic said.

In June, Advancis signed a definitive agreement with Par Pharmaceutical Inc., of Spring Valley, N.J., a subsidiary of Par Pharmaceutical Companies Inc., as its partner to develop and commercialize Amoxicillin Pulsys, finalizing a letter of intent reported in March.

More than 62 million prescriptions for amoxicillin were written in 2003 and the antibiotic has had more than 1 billion total patient exposures. Indicated for a range of infections, the drug is commonly prescribed as a first-line therapy for common infections such as otitis media (middle ear infection), pharyngitis (sore throat), and sinusitis (sinus infection).

According to data from IMS Health, a pharmaceutical research company, annual U.S. amoxicillin sales are about $500 million, with about one-quarter of total amoxicillin prescriptions written for pharyngitis, strep throat, and tonsillitis for both adults and children.

"It was the sixth most prescribed drug last year," Rudnic said, even with physicians becoming less quick to offer antibiotics due to a growing resistance problem. Doctors are "much tighter" with prescriptions "but you have to understand that antibiotics have a role to play in keeping people from developing very serious infections and having to go to the hospital," he said.

Even so, patient compliance can be a problem.

"Almost half of the antibiotic regimens prescribed in the U.S. are not being complied with," Rudnic told BioWorld Today. "That's a tremendous amount of inefficient dosing. If you think about it, for the first five days you're motivated because you're sick, and for the last five days you're not so motivated." Some dosing regimens extend for two weeks.

The Pulsys technology should help in that regard, too - with amoxicillin and other antibiotics. In June, Advancis paid $11 million to acquire exclusive U.S. rights to the Keflex brand of cephalexin from Eli Lilly and Co., of Indianapolis.

"We expect to have a once-per-day product in the clinic next year," Rudnic said. Keflex Pulsys is likely to reach the market about a year after the amoxicillin version, he said. The Lilly drug "has been over-genericized, and Lilly had let that go for a bit," Rudnic noted. Keflex sold only $4 million last year.

"We think we can build the brand back," he said. Cephalexin is a cephalosporin antibiotic used to treat bacterial infections such as pneumonia and those of the bone, ear, skin and urinary tract.

Advancis also has a deal with London-based GlaxoSmithKline plc for the development, manufacture and sale of a Pulsys version of its strong-selling antibiotic Augmentin (amoxicillin with potassium clavulanate). Augmentin sold $700 million for GSK last year, "even though it was under tremendous generic attack."

GSK expects to take the Augmentin Pulsys into Phase III trials next year, and Advancis is due $49 million in development milestones over the next years, plus $50 million in sales milestones apart from royalties.

The fewer-dosing advantage is one widely hailed with regard to the antibiotic Zithromax (azithromycin), New York-based Pfizer Inc.'s five-day pill approved in the U.S. in 1992.

"Zithromax is an OK antibiotic, but its real benefit is convenience," Rudnic said. "We know that for the indications we're going after, amoxicillin is a better antibiotic than azithromycin." So, for that matter, is cephalexin, he said.

Advancis has "11 products in development, with six in human trials," Rudnic said - not bad for a company that's not quite five years old with 100 employees. The firm went public last October, raising $60 million.

"We've been working on amoxicillin for about four years," he said, adding that the company "[continues] to have discussions with big pharma about improving antibiotics that are still under patent."

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