Nektar Therapeutics announced that the first subjects were dosed in a Phase 1 clinical study for NKTR-171, a new sodium channel blocker being developed as an oral therapy for the treatment of peripheral neuropathic pain. The single-ascending dose Phase 1 clinical study of NKTR-171 will assess its pharmacokinetics, tolerability and safety in up to 50 healthy subjects. NKTR-171 is a new molecular entity that is specifically designed to treat neuropathic pain by blocking hyperactive neuronal sodium channels associated with damaged nerves in the peripheral nervous system.

Chronic neuropathic pain arises from nerves injured or damaged by systemic disease, infection, toxins, or physical trauma that are in a continuous state of hyper-excitability, often due to aberrant sodium channel firing. This hyper-excitability results in transmission of abnormal pain signals from the periphery to the central nervous system (CNS).(1) Existing therapies that block sodium channels have been shown to provide effective pain relief but are typically associated with significant unwanted CNS side effects, including dizziness, ataxia and somnolence. NKTR-171 is designed to be a peripherally-restricted molecule which selectively blocks hyper-excitable sodium channels without causing the CNS side effects that limit usage of existing therapies.

In preclinical studies, NKTR-171 demonstrated an improved efficacy and CNS side effect profile when compared to pregabalin (Lyrica(R)) (2,3) NKTR-171 also exhibited significantly reduced CNS penetration versus currently-approved sodium channel blockers. Neuropathic pain, also known as nerve pain or peripheral neuropathy, is the result of nerve damage and can be caused by such diverse conditions as diabetes, shingles, cancer, HIV, multiple sclerosis and fibromyalgia, as well as injury or trauma to the nerves.