Washington Editor

The anti-infective firm Replidyne Inc. filed for broad FDA approval of Orapem, an oral prodrug derivative of faropenem, seeking clearance for acute bacterial sinusitis, community-acquired pneumonia, acute exacerbations of chronic bronchitis and uncomplicated skin and skin structure infections.

"The primary focus is respiratory tract infections," Jill Clark, Replidyne's senior director of finance and administration, said. "Skin is in addition to that."

The new drug application, which marks the first submission for Orapem worldwide, is the Louisville, Colo.-based company's first regulatory filing. It was submitted electronically last month in the common technical document format, meaning that it can be sent for approval in other territories around the world.

But Clark told BioWorld Today that Replidyne's plans are focused only on the U.S. right now, adding that the submission "takes us to another level as a company." Now planning commercial activities for the first time, privately held Replidyne is contemplating partnership opportunities to supplement internally driven promotional efforts in advance of Orapem's hoped-for approval, which Clark said could come late this year after a standard review period.

Market estimates put annual spending on branded respiratory tract infection products in the U.S. at $8.5 billion

Replidyne acquired Orapem's exclusive rights in March 2004 from Daiichi Asubio Pharma Co. Ltd. for the U.S. and Canada, as well as an exclusive option on the rest of the world except Japan. Clark declined to say whether the filing triggered a milestone payment.

The NDA is based primarily on data from 11 Phase III trials that assessed Orapem's clinical and microbiological efficacy, as well as its safety and tolerability profiles in treating respiratory tract and skin infections. The safety database alone includes more than 5,000 Orapem-treated patients, but Clark declined to discuss data from the trials.

If approved, it would be the first oral antibiotic of the penem class to be marketed in the U.S. Faropenem, its primary ingredient, is the only orally bioavailable penem drug. The prodrug offers better oral bioavailability and leads to higher systemic concentrations of the drug, Replidyne said.

Replidyne has planned additional studies to test higher doses of Orapem for shorter durations of therapy, as well as other indications for the product. For example, the company already is clinically testing a suspension formulation to treat pediatric patients, initially for otitis media or ear infections.

Orapem was discovered by scientists at Suntory Institute for Biomedical Research, now part of Tokyo-based Daiichi Asubio, and is manufactured there by Nippon Soda Co. Ltd.

Beyond Orapem, Replidyne's pipeline includes a topical antibacterial product, REP8839, which uses a new mechanism of action to address methicillin-resistant Staphylococcus aureus (MRSA). Clark said the company plans to file an investigational new drug application in the first half of this year, with early clinical studies to follow. Replidyne also has discovery programs directed toward inhibiting bacterial DNA replication, which could result in therapies to treat a range of antibiotic-resistant bacteria.

In September, the company raised $62.5 million in a Series D financing, one of the industry's largest rounds of the year. To date, it has brought in $121.5 million.