TOPOFEN™: Achelios’ Proprietary Transdermal Ketoprofen Formulations
TOPOFEN™ is a clinical stage product that pairs Achelios’ powerful transdermal drug delivery technology system, TOPOGEL™, with ketoprofen, a well-established non-steroidal anti-inflammatory molecule. Ketoprofen has been used globally for a long period of time; consequently, significant safety and efficacy data are available. These data are based on both the orally ingested tablet form of ketoprofen, as well as the topical gels that are available today via prescription. TOPOFEN™ is formulated as a 5% ketoprofen gel for topical use in acute migraine, whereas the current, acute treatment options in migraine (triptans) are primarily prescribed in oral form. Botox®, another therapeutic in the broader marketplace, differs from traditional migraine treatments in that it is used prophylactically. Since its approval for this indication, it has captured market share from certain acute therapies due to its ability to prevent migraine attacks from occurring. As Botox® is an injection it must be administered by a qualified healthcare professional.
The main driver of differentiation for TOPOFEN™ is provided by Achelios’ proprietary, patent-protected transdermal drug delivery system. This platform, TOPOGEL™, delivers substantially greater amounts of active ingredient than current topical delivery systems, thus making it an alternative to oral delivery. In clinical trials the product was generally well tolerated, and has shown no photosensitivity in animals or humans. Additionally, TOPOFEN™ is expected to yield a reduced incidence of serious gastrointestinal, cardiac, renal, and hepatic side effects commonly associated with oral ketoprofen therapies, all while maintaining clinical efficacy.
As TOPOFENTM delivers substantial amounts of drug into the underlying tissue, topical treatment of disorders that require effective levels of drug in the deeper tissue layers has become possible. Apart from the classic target indications of osteoarthritis and sprains and strains, and also TMJ disorders, TOPOFEN™ also generated promising results in clinical trials in acute migraine, and is being considered for use in migraine prophylaxis. TOPOFEN™ has the potential to take significant market share from the current standard of treatment for acute migraines due to its strong efficacy and safety profile, as well as its ease of administration. The potential use of TOPOFEN™ in migraine prophylaxis is an opportunity to generate additional value.
Mechanism of Action
Non-steroidal anti-inflammatory drugs (NSAIDs), including over-the-counter NSAIDs such as aspirin, ibuprofen, naproxen, and ketoprofen, have been used for over 20 years to treat acute migraine attacks. All of these agents have a common property: they inhibit prostaglandin synthesis and thereby reduce the consequences of the inflammatory reaction. The headache phase of migraine is thought to develop as the result of an abnormal interaction (and perhaps an abnormal release) of vasoactive neurotransmitters from terminals of the trigeminal nerve with large intracranial and extracranial blood vessels. By modulating neurotransmitter release, NSAIDs inhibit sympathetic neural transmission. They also promote the contraction and relaxation of vascular smooth muscle, enhance vascular permeability, and mediate the actions of other vasoactive substances. On balance, these actions are effective in reducing migraine pain.