Akari announced that votucalis has potential as a treatment for pain and itch associated with conditions such as atopic dermatitis, psoriasis and neuropathic pain.
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Headquartered in both New York and London, Akari Therapeutics has built its therapeutic portfolio with pharmaceuticals targeting dermatology, orphan autoimmune and inflammatory diseases. The company specifically seeks to develop drugs that combat afflictions in the complement or leukotriene system, which work collaboratively in the mechanics of the immune system.
The newest addition to the collection of drug candidates is votucalis, a broad spectrum antihistamine that has shown promise in preclinical model data involving mice. The data was published in Frontiers in Pharmacology.
The activation of histamine receptors afflicts a large portion of the global population, resulting in chronic pain or itch and generalized inflammation. While most currently marketed antihistamines target two of the available histamine G-protein coupled receptors (H1 and H2), votucalis works to inhibit all four target receptors: H1, H2, H3 and H4.
Despite affecting each receptor protein at different percentages, the average reduction of itch symptoms and sensations was shown to be between 80% and 90% when coupling votucalis with peripheral antagonists. The high efficacy of inhibition comes as votucalis captures and binds to histamine, the key operator in inflammatory responses. This inhibition was shown to be withstanding for long durations. Akari hopes to explore higher dosages, potentially resulting in even higher efficacy in diminishing itch sensations.
Clive Richardson, CEO and COO of Akari, said in a press release that the drug highlights the potential for votucalis “where current treatments such as opioids can be ineffective and can have serious side-effects, including addiction.”
Much like current methods of opioid administration, votucalis proved to be much more effective when locally administered to patients, rather than systemic administration through oral dosages. Akari hopes to also explore topical methods of administration, expanding the drug’s potential to patients not willing to be injected with another drug. Topical use of the drug has shown promise in human skin cadaver experiments.
When exploring the pharmacokinetics of votucalis, it is seen that the central nervous system is not affected, another key point to be made in the argument for votucalis versus opioid prescriptions. Opioids have been seen to be detrimental to the central nervous system of those who are chronically prescribed.
The discovery of votucalis came alongside research for Akari’s phase III clinical-stage drug, nomacopan, a c5 complement inhibitor that affects leukotriene B4 activity. Current indications and clinical evaluations for nomacopan include bullous pemphigoid, thrombotic microangiopathy and other eye and lung diseases. Upon receiving confirmation of the safety and efficacy of nomacopan, Akari may open up the drug for expanded access programs, rather than limiting its use to clinical trials.
Nomacopan is currently indicated as a locally injectable drug in its late-stage trials. Durham University and Newcastle University are collaborating to work towards a clinical program to explore this new indication for nomacopan by the end of 2022. Akari hopes to use the same collaborations to move forward with research and possibly phase I studies for votucalis.
If successful, a broad-based antihistamine targeting all receptors is likely to be highly marketable for a variety of indications.
