Recent research suggests that low doses of psychedelic compounds such as LSD and ketamine can help alleviate pain. Could therapies that use small amounts of these substances be the future of pain management?
Bexson Biomedical believes that its system for delivering low doses of ketamine may provide an effective alternative to opioid-based pain relief strategies which have greater potential for addiction. The company has teamed up with the device manufacturer Stevanato Group to create a wearable ketamine delivery device for patients who need short term relief from chronic and acute pain after receiving surgery. The device and its proposed ketamine therapy are still in the early stage of research.
“Post-operative pain is one of the leading drivers in the opioid crisis. If you want to move the needle on opioid addiction in America you need to provide a new, non-opioid therapy that patients can go home with that has opioid-level efficacy,” Gregg Peterson, Chief Executive Officer at Bexson, told Forbes. “We think our product will be able to do that.”
According to Bexson, doctors are already providing ketamine for postoperative pain relief through intravenous infusions at clinics or hospitals that allow for “steady state plasma levels” or a consistent level of effective pain relief. Megan Oxley, an emergency physician and vice president of the American Society of Ketamine Physicians, says that for relief from the type of acute pain that a person would experience after breaking a leg or recovering from surgery “steady state [plasma] levels probably do allow for better pain control.”
Patients who are discharged from the hospital are not typically offered ketamine infusions by medical providers. While some people use ketamine lozenges for pain relief, patients are instead often prescribed opioids.
Oxley says Ketamine infusions also aren’t offered for home because this form of administration needs to be monitored. “Chronic pain can certainly be treated with other forms of ketamine at home. It is harder to treat acute pain with the current home options but it can be done,” says Oxley.
The new technology now being developed by Bexson is a customized modification of Stevanato’s patented SG EZ-be Pod portable insulin delivery device. It includes a disposable pod containing between 20 and 70 milligrams of ketamine, a needle, and a Bluetooth-enabled control unit that slowly delivers the dose over a period of 24 hours. According to Bexson, the pod has anti-tampering technologies that prevent the user from increasing the intended dosage, whether by mistake or deliberately. Bexson did not provide detailed information about how these anti-tampering systems are expected to operate.
The Bexson device delivers ketamine subcutaneously, which means it enters the layer of fat between the skin and the muscle. To increase the bioavailability of ketamine through this method, Bexson is developing a proprietary formulation of ketamine, BB106, with a higher pH. Company co-founder Jeffrey Becker, who is a psychiatrist, emphasizes that the system provides a low dose of ketamine, rather than a microdose, adding that the company is “not currently developing a `microdose’ use case.”
Bexson says it is targeting the $12 billion dollar market for post-operative pain control. The company will start animal testing on its ketamine delivery product this year and plans to launch a phase one clinical trial in 2021. It has not yet released peer reviewed research demonstrating the effectiveness of its BB106 formulation.
Medical researchers are raising questions about potential damage to the epithelial lining of the bladder caused by sustained ketamine use in different kinds of therapies and usage patterns. Researchers have not flagged any specific concerns about the Bexson device.
Bexson believes that its device could gain FDA approval by 2026. In the meantime, the company says it is devising ketamine formulations to target other conditions, including mental health treatments. Based on its present research plan, Bexson is in the process of closing a Series A funding round, its first significant round of venture capital funding.
Propriety formulations and patented delivery systems can sometimes increase the cost of ketamine-based therapies. Spravato, the prescription esketamine nasal spray developed by the Janssen Pharmaceuticals unit of Johnson & Johnson for treatment resistant depression (TRD) and major depressive disorder (MDD), is administered in 28 mg, 56 mg, or 84 mg doses. A full 84 mg dose can cost $850 with an induction regimen that includes two treatments a week for three weeks. This does not include the cost of two hours of supervision which are required by the FDA and the manufacturer.
According to a Bexson spokesperson, the company has not yet identified a price point for their ketamine delivery device for pain relief. As it is not a mental health treatment, patient care is expected to follow a different model. According to a statement by Steven Kaufman, Vice-President of Drug Delivery Systems for the Stevanato Group, the modified SG EZ-be Pod device will help keep treatment costs down. “This design will support patient comfort with a discreet and intuitive device, and by utilizing our patented technologies, we address the importance of sustainability, while minimizing the overall cost per treatment,” said Kaufman.
“I believe, this is my opinion, because you are using the cheaper generic version of ketamine, the administration system is the expensive and patented part,” says Oxley, the physician. “But you can price it however you want and make sure you are lower than your competition. Remember Spravato is a patented medication, Bexson created a delivery device, but is using a generic old medication.”
Ketamine was first used as a veterinary anesthetic in 1963. Research strongly suggests that ketamine can also be a fast-acting and highly effective antidepressant. Patented for human use in 1966 and approved four years later by the FDA, ketamine has a long history of use as an anesthetic beginning with the treatment of soldiers during the Vietnam War. Together with a team of investigators, Dr. Carlos Zarate, a psychiatrist working at the National Institute of Mental Health (NIMH) published in 2006 seminal research on the use of IV ketamine as a therapy for treatment-resistant depression.
Medical professionals like Oxley offer ketamine off-label for mental health treatments as intramuscular injections, IV treatment or via lozenges. The National Institute of Mental Health (NIMH) investigated ketamine for the treatment of depression. The Yale University School of Medicine developed what is known as the NIMH protocol which uses .05 mg/kg per 40 minutes IV dosage for treatment-resistant depression which is typically repeated over the course of six treatments in two or three weeks.
Becker, who serves as Chief Scientific Officer at Bexson, says that when Bexson’s ketamine delivery device is tailored for mental health conditions instead of pain relief, the “doses may be higher as is clinically appropriate.” Specific doses will be fine-tuned based on data from Phase I and II studies.
Peterson told Forbes that the ketamine dosage delivered by the Bexson device for pain relief will result in a mild altered state similar to ingesting “a glass of wine, maybe a martini.” But according to Bexson, the device will support dosage control and reduce the need for patient monitoring.
Becker asserts that “ketamine is not as easy to abuse [as opioids]” and notes that the device’s delivery method only makes low doses available to patients,. which is key to the device’s safety.
While prescription opioid painkillers are one of the most common treatments for postoperative pain, these medications are a major factor in the opioid crisis in the U.S., which sees increasing numbers of people succumbing to opioid addiction and sometimes fatal overdose. Peterson told Lucid News that by “providing an effective non-opioid therapy for at home use, we believe we can reduce opioid addiction rates, and ultimately opioid-related overdose deaths.”
Elias Dakwar, an associate professor of Clinical Psychiatry at Columbia University, agrees that this delivery method reduces the chances for the type of addiction patterns that patients encounter with opioids.
“Low dose infusions of ketamine have a very low potential for being abused given reduced psychoactive effects. They have been used in pain management settings for many years in inpatient settings, without incidence of abuse,” says Dakwar. “It is likely that their use in outpatient settings through a device will be similarly safe.”
Given that the anticipated dose of ketamine for Bexson’s device may still produce mild psychoactive effects, Dakwar recommends that users avoid operating any heavy machinery and driving when the infusion itself is taking place. Low dose infusions of ketamine, says Dakwar, “are known to address chronic pain, acute pain, and refractory pain; they may also reduce the need for opioids, without necessarily replacing them altogether.”