Therapy Analysis - Drug Reprofiling
A winning combination?
Another approach to drug reprofiling is the discovery of
synergistic combinations of existing drugs, which can be
used to treat new indications or increase efficacy in existing
ones. One of the leaders in this field is the aptly-named
US company CombinatoRx. This company specialises
in producing combination drug candidates with
new mechanisms of action, based on the synergism of
the constituent drugs and targeting of multiple disease
pathways in a broad range of disease areas.
CombinatoRx' lead candidate is CRx-102, an oral product combining the long-established steroid prednisolone with the equally well-known antithrombotic dipyridamole utilising controlled-release technologies. It is in development for the treatment of osteoarthritis (OA), rheumatoid arthritis (RA) and periodontitis. The rationale for such a product is based around the fact that dipyridamole amplifies the therapeutic activity of prednisolone, without concomitantly increasing side-effects. Additionally, the physiological effects of these products separately are well-documented, removing a major uncertainty as to what these compounds will do once they are administered together to patients. In a Phase IIb trial (COMET-1) in 279 symptomatic knee OA patients, interim results showed a trend in favour of CRx-102, although the change in WOMAC score did not reach significance. Results from an intent-to-treat analysis, however, showed high-dose CRx-102 provided various treatment benefits. In a Phase IIa trial in 59 RA patients, CRx-102 in combination with disease-modifying antirheumatic drugs gave significant improvements in CRP levels as well as ACR20 and DAS28 responses. It also proved to be well-tolerated, with no serious adverse events reported. Pivotal Phase III trials in OA patients are planned for the first half of 2009.
Another promising candidate from CombinatoRx' pipeline is FOV-1101, a topical combination of enhanced steroids, in development for the treatment of ocular diseases. It is licensed to the specialty ophthalmic company Fovea, with CombinatoRx retaining development and commercialisation rights in North American and certain other countries, as well as co-development rights in Japan and Taiwan. FOV-1101 is currently in preclinical development, with clinical trial initiation expected very soon.
