Topical TV-45070 8% ointment in herpes zoster pain not effective
Teva Pharmaceutical Industries Ltd. at the end of June 2017 disclosed the results of a Phase II study analysing topical TV-45070 4% and 8% oil in patients with post-herpetic neuralgia (PHN). The ointment treatment (twice a day) did not reduce the primary endpoint, pain measured via the NRS, at week four compared to placebo. However, there were no side effects.
The study was carried out at 48 centers in the US and involved 300 patients randomized to 100 patients receiving 4% TV-45070, 100 patients receiving 8% TV-45070 and 100 patients receiving placebo.
TV-45070: a sodium channel Nav 1.7 inhibitor
TV-45070 is a small-molecule inhibitor of the sodium channel Nav1.7, expressed in the pain-sensing peripheral nervous system.
This is unfortunate for TEVA, but on hindsight PHN might also not be the best indication due to the specific pathogenesis and the mechanism of action of topical sodium channel blockers.
Phenytoin cream for neuropathic pain
In the same class as the TEVA compound we find phenytoin.
Phenytoin however is a broad acting sodium channel blocker with additional mechanisms of action, and formulated in cream might have certain advantages, and might be more fit to influence the specific targets in the skin.
The datapool of patients treated with phenytoin cream is growing and Topical Innovations reached already 50 patients, all described in great detail. At the Neupsig in Gothenburg (June 2017) there was also much interest in these recent findings.
Literature on topical phenytoin
- Keppel Hesselink JM, Kopsky DJ. Topical phenytoin cream reduces burning pain due to small fiber neuropathy in sarcoidosis. J Anesth Pain Med. 2017; 2(1): 1-3. (PDF)
- Keppel Hesselink JM. Amantadine and phenytoin: patent protected cases of drug repositioning Clin Invest. 2017; 7(1):11-16.
- Keppel Hesselink JM, Kopsky DJ. Bottlenecks in the development of topical analgesics: molecule, formulation, dose finding, and phase III design. J Pain Res. 2017; 10: 635-641. (PDF)
- Keppel Hesselink JM, Kopsky DJ. Burning pain in small fibre neuropathy treated with topical phenytoin: rationale and case presentations. J Clin Anesth Pain Med. 2017; 1(1): 6. (PDF)
- Kopsky DJ, Keppel Hesselink JM. Phenytoin in topical formulations augments pain reduction of other topically applied analgesics in the treatment of trigeminal neuralgia. J. Clin Anesth. 2017; 38: 154-155.
- Keppel Hesselink JM, Kopsky DJ. Topical phenytoin in neuralgic pain, peripheral modulation of central sensitization: two case reports. J Pain Relief 2017; 6(2): 284. (PDF)
- Kopsky DJ, Keppel Hesselink JM. Topical phenytoin for the treatment of neuropathic pain. J Pain Res. 2017; 10:469-473. (PDF)
- Keppel Hesselink JM, Kopsky DJ. Phenytoin: 80 years young, from epilepsy to breast cancer, a remarkable molecule with multiple modes of action. Journal of Neurology. 2017:1-5.
- Keppel Hesselink JM, Kopsky DJ, AK Bhaskar. Skin matters! The role of keratinocytes in nociception: a rational argument for the development of topical analgesics. J Pain Res. 2017; 10:1-8. (PDF).
- Keppel Hesselink JM. Thinking out of the pillbox: the relevance to topiceuticals in the treatment of neuropathic pain. J Pain Relief 2016; 6(5): (PDF).
- Keppel Hesselink JM, Kopsky DJ, Sajben NL. New topical treatment of vulvodynia based on the pathogenetic role of cross-talk between nociceptors, immunocompetent cells and epithelial cells. J Pain Res. 2016; 9: 757-762. (PDF)
- Keppel Hesselink JM, Kopsky DJ. Topical analgesic creams and nociception in diabetic neuropathy: towards a rationale fundament. Clin Case Rep Rev. 2016; 2(7): 500-502. (PDF)
- Kopsky DJ. Topical analgesia is a viable option. J Pain Relief 2016; 5(3):245. (PDF)
- Kopsky DJ. Extending the therapeutic scope for the treatment of neuropathic pain with topical analgesics. J Pain Relief. 2016; 5(3): 251-252. (PDF)