Wafermine: the world’s first patented sublingual racemic ketamine wafer for pain and depression
iX Biopharma is transforming approved drugs such as ketamine into novel therapies using its wafer-based sublingual technology, to develop therapies for pain, depression and more.
Since its establishment in 2008, iX Biopharma has used its patented wafer-based delivery platform technology, WaferiX, to develop novel sublingual drugs for pain and other conditions. The company’s lead drug candidate utilizing WaferiX is Wafermine, the world’s first patented sublingual racemic ketamine wafer for the treatment of acute moderate to severe pain and major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate antagonist, has only been approved for use as an anesthetic administered via intravenous (IV) injection in 1970 and has since been used off-label for the management of acute and chronic pain and depression.
In light of the opioid epidemic gripping the USA and many other parts of the world, Wafermine is a timely and much-needed drug, as it can be used both as an adjunct to opioids or as a substitute. When used with opioids, ketamine has been shown to reduce opioid use owing to its dose-sparing effect. Furthermore, compared with opioids, which, when misused, can cause respiratory depression leading to death, low-dose ketamine is a safer option as it does not affect the respiratory system. “Against the background of the opioid epidemic, the time for ketamine, a nonopioid drug, is now,” said Janakan Krishnarajah, iX’s COO.
Wafermine is developed under the US Food and Drug Administration (FDA) 505b(2) New Drug Application (NDA) pathway for acute moderate to severe pain. A phase 2b study in moderate to severe acute, postoperative pain confirmed that Wafermine has strong analgesic efficacy and is safe and well tolerated in patients; an end-of-phase 2 meeting with the FDA has been scheduled in Q3 2019 to evaluate the phase 3 program.
Although Wafermine is an unregistered drug, iX has been supplying Wafermine to hospitals in Australia since 2014 under a regulatory exemption for use by specialists to treat pain, with excellent results and safety. Stephan Schug, chair of Anaesthesiology and Pain Medicine at the Medical School of the University of Western Australia and director of Pain Medicine at the Royal Perth Hospital, Australia, said, “Our pain service is using sublingual ketamine in the acute setting with excellent efficacy and minimal adverse events.”
In addition to pain, Wafermine is ready for phase 2 trials in MDD. In recent decades, racemic ketamine has also proved to be effective for treatment-resis¬tant depression (TRD): IV ketamine is used off-label to treat depression in the European Union, USA and Australia; and Janssen’s Spravato, an intrana-sal esketamine, was recently approved for use in combination with antidepressants for TRD. “While oral antidepressants take weeks to start having an effect, the ketamine delivered by Wafermine takes only hours and without the need for IV administra-tion—it’s simply placed under the tongue,” said Krishnarajah. “As well as effectively treating TRD, Wafermine could be used as a bridging initiation therapy in more severe MDD.”
WaferiX sublingual delivery
The sublingual wafers are made at iX’s research and development and manufacturing center in Melbourne, Australia using a proprietary freeze-drying manufacturing process (Fig. 1). WaferiX comprises a choice of matrix-forming agents and
has been carefully designed to minimize dissolution time, maximize the extent of full dissolution of all components, maximize the rate of transfer of bio-logical active to the sublingual mucosal membrane, optimize the contact time of the biological active with the sublingual mucosal membrane and minimize the fraction of biological active inadvertently swallowed by the patient.
When introduced to the moisture in the oral cavity, the wafer disintegrates rapidly and releases the active compounds for absorption through the thin epithelial layer under the tongue directly into the body’s systemic circulation via the jugular vein. This allows the active compounds to truly bypass the gastrointestinal tract (where there is high variabil¬ity in absorption owing to pH effects, type of food consumed, gut flora and more) and the hepatic first-pass effect (where many bioactives are degraded or removed by liver enzymes).
Versatile and flexible, WaferiX can be used to formulate a wide variety of small-molecule drugs. iX has a portfolio of innovative WaferiX-based products, including sildenafil, buprenorphine and cannabis sublingual medications. Its sildenafil sublingual wafer, Wafesil, for the treatment of erectile dysfunction, is registered in Australia, validating the robustness and utility of WaferiX technology for the formulation of pharmaceutical drugs.
Advancing Wafermine through partnering
iX is looking for partners to advance Wafermine through its phase 3 program in pain and/or its phase 2 program in MDD. “Wafermine is a unique drug that targets two large addressable markets and unmet clinical needs. The commercial and develop¬ment risk is low given that Wafermine is in late-stage development, ketamine’s safety is already established as an approved drug and its effectiveness as a pain medication well demonstrated from clinical experience,” pointed out Krishnarajah.
Eva Tan, Director of Corporate
and Commercial Strategy
iX Biopharma Ltd
Tel: +65 6235 3212