Diclofenac (Intravenous)

Reformulated diclofenac has the potential to target neuropathic pain

Cutting-edge science and differentiation

In 2001, Javelin acquired the rights to technology that employed hydroxypropyl beta-cyclodextrin to solubilise diclofenac with the result that diclofenac can be administered as a single intravenous bolus (Dyloject) within five seconds. New teachings by McCormack showed that because peak levels of Dyloject are achieved almost instantaneously, the pharmacology of Dyloject is unique and very different to that of oral or slowly-infused diclofenac. McCormack identifies a new and previously-unknown pharmacology in which it is argued that the analgesic action of Dyloject uniquely involves the coincident, but not necessarily simultaneous effects upon both cyclooxygenase and a newly-discovered ion channel (the outcomes of published phase II studies by Javelin suggested the co-involvement of cyclooxygenase-independent mechanisms).

Clinical implications of new teachings

With this new pharmacology McCormack designed a novel formulation to exploit and enhance the the ion channel-mediated effects of Dyloject. This new formulation of Dyloject would enable, for the first time, an NSAID with the capacity to attenuate neuropathic pain (a high unmet need). With the subsequent acquisition of Javelin by Hospira, this Javelin-sponsored program of work was discontinued.

These exciting findings offered the prospect of profound value-differentiation for the use of Dyloject in several subgroups, including patients with some types of chronic pain. Novel effects were proposed together with the prospect of significant benefits associated with a new NSAID formulation that in clinical practice may show dose-related non-superimposable efficacy and toxicity dose-response curves. That is, efficacy could be achieved independently of toxicity. However, the existing posology and composition of Dyloject would need to be modified as McCormack’s original teachings indicated.

Key outcomes

• Prospect of new IP within a new indication (chronic pain/neuropathic pain)