Replidyne is developing faropenem medoxomil, the ester-type prodrug of faropenem, for the treatment of bacterial infections
and respiratory tract infections, including acute exacerbations of chronic bronchitis (AECB), acute bacterial sinusitis (ABS)
and community-acquired pneumonia (CAP). Faropenem medoxomil is also being developed for the treatment of tonsillitis, pharyngitis
and otitis media in children. Faronpenem medoxomil was discovered by scientists at Suntory Institute for Biomedical Research
(now Asubio Pharma). The compound has significantly improved oral bioavailability and is dehydropeptidase-I stable. Following
absorption, faropenem medoxomil is rapidly hydrolysed to the active drug faropenem. An NDA was filed in the US but was deemed
not approvable by the US authorities. Following the termination of the license agreement between Replidyne and Forest Laboratories,
Replidyne is now exploring other partnering opportunities for faropenem medoxomil. Daiichi Suntory Pharma (now Asubio Pharma)
has granted Replidyne the exclusive rights to faropenem medoxomil for the US and Canada and an exclusive option to develop
and commercialize the compound in the rest of the world, excluding Japan. Replidyne has rights to the preclinical and clinical
data generated up to the time of the agreement (August 2004) and will complete clinical development of the drug. Replidyne
is also developing a paediatric formulation for the treatment of common bacterial infections. In February 2006, Replidyne
sublicensed development, commercialization and distribution rights of faropenem medoxomil in the US to Forest Laboratories
Holdings (Forest Laboratories). However, the agreement was terminated in February 2007, following the US FDA's non-approvable
letter for the product. Replidyne re-acquired all US adult and paediatric rights previously granted to Forest. Bayer AG previously
licensed exclusive worldwide rights to develop faropenem medoxomil from Suntory (now Asubio Pharma) and conducted a number
of phase III clinical trials. This agreement appears to have been superseded by the agreement with Replidyne in 2004. In April
2007, Daiichi Asubio Pharma was renamed as Asubio Pharma Co., Ltd. Daiichi Asubio Pharma was the name used by Daiichi Suntory
Pharma after it became a wholly owned subsidiary of Daiichi Pharmaceutical in September 2005. Daiichi Suntory Pharma was the
joint venture company owned by Daiichi Pharmaceutical and Suntory. In April 2006, Daiichi Pharmaceutical merged with Sankyo
to form Daiichi Sankyo Inc. The FDA issued a non-approvable letter in October 2006 for faropenem medoxomil in the treatment
of ABS, CAP, AECB and uncomplicated skin and skin structure infections. Consequently, drug development has reverted back to
phase III in the US. The agency has indicated that four phase III trials in three adult respiratory indications, ABS, CAP
and AECB, will be required for a US marketing application. According to this advice, Replidyne may be required to conduct
one superiority study (versus placebo) each for the ABS and AECB indications and two non-inferiority, active-controlled studies
for the treatment of CAP. The required dose of faropenem medoxomil in future trials will be 600 mg, administered twice daily,
and trials will involve approximately 1500 patients to ensure an acceptable database of safety information for review. Replidyne
is continuing to work with the FDA on further trial details. Replidyne first filed the NDA seeking approval for faropenem
medoxomil in December 2005. This submission marked the first marketing approval application for faropenem medoxomil worldwide.
The NDA, which was accepted in February 2006, was primarily based on data from 11 phase III trials in patients with respiratory
tract and skin infections; the safety data included information from more than 5000 patients treated with the drug. The proposed
commercial name for faropenem medoxomil, Orapemtrade mark, was not approved by the FDA due to its similarity to another commercially
approved drug. Replidyne and the FDA are working together to identify a suitable alternative. Two phase III trials have been
conducted that demonstrated faropenem medoxomil was non-inferio o azithromycin and clarithromycin in the treatment of AECB.
Replidyne's phase II trial evaluating an oral liquid formulation of faropenem medoxomil (7.5-40 mg/kg) in paediatric patients
with acute otitis media (AOM), met its primary endpoint. The trial was completed in March 2007 and enrolled approximately
310 patients in Costa Rica and Israel. Replidyne intends to meet with the US authorities to discuss the design of the planned
phase III trial in paediatric AOM. In addition to 5 years of Hatch-Waxman exclusivity granted upon approval, faropenem medoxomil
is protected by an issued US composition of matter patent, which expires in 2015. Extension of exclusivity under Hatch-Waxman
legislation is expected.