Along with electing Donald J. Trump as the United States’ 45th president in the Nov. 8 election, the legal cannabis industry scored landmark victories in concurrent ballot measures in several states, raising hope for those who support developing new cannabis-based therapies for unmet medical needs, especially in the management of chronic pain.
Use of recreational cannabis is now legal in California, creating the nation’s largest market for legalized pot, as well as in Nevada and Massachusetts. With recreational marijuana use already legal in Colorado, Washington State, Alaska, Oregon and Nevada, and medical cannabis legalized in 20 more states and the District of Columbia, some 20% of Americans can legally use recreational cannabis. According to a FinancialBuzz.com press release, citing poll data indicating that about 60% of Americans now support cannabis legalization, nearly doubling the corresponding metric of 31% in 2000.
FinancialBuzz.com projects markets for both recreational and medicinal cannabis to grow to $22 billion by 2020, with November’s election results potentially influencing other states to consider reforming their laws prohibiting cannabis, and may even help persuade the federal government to lift its ban.
However, the report notes that uneven regulations among states regarding legal cannabis creates complexities for both governments and businesses involved. For example, governments are collecting new tax dollars from cannabis companies, but because of the federal cannabis ban, these same companies often are unable to open bank accounts, greatly complicating their operations.
The report also notes that the cannabis market is becoming more diverse in scope and focus. For instance, Zynerba Pharmaceuticals is a clinical stage specialty pharmaceutical company, and developer of next-generation synthetic cannabinoid therapeutics for transdermal delivery in the treatment of patients with high unmet medical needs, including those living and suffering with fibromyalgia and peripheral neuropathic pain, epilepsy, Fragile X syndrome and osteoarthritis.
Devon, Pa.-based Zynerba notes that oral administration of medical marijuana can lead to limitations in safety and efficacy, including low bioavailability, inconsistent plasma levels and significant first-pass liver metabolism. That is a process in which the liver breaks down therapeutics ingested directly or indirectly through the gastrointestinal system, such as through oral or oral mucosal delivery methods, allowing only a small amount of drug to be absorbed into the circulatory system.
Conversely, transdermal therapeutics are absorbed through the skin directly into the systemic circulation. That delivery method avoids first-pass liver metabolism and potentially allows lower doses and more consistent blood levels with fewer peaks and valleys, resulting in enhanced efficiency and a better tolerability profile.
Zynerba is concentrating on two product candidates, ZYN002 and ZYN001, over these five indications, and planning a Phase 1 clinical trial projected to begin in the first half of 2017 to study ZYN001 — a pro-drug of THC (tetrahydrocannabinol) that may provide once-daily dosing and enables transdermal delivery via an easy-to-apply patch in patients with fibromyalgia and peripheral neuropathy.
Pro-drugs are agents designed to enable more effective delivery, then converted in the body into different forms through normal metabolic processes.
In October, Zynerba announced it is working with LTS Lohmann Therapie-Systeme AG of Andernach, Germany, and West Caldwell, N.J. — a market leader in transdermal therapeutic solutions, to collaborate on optimizing the formulation of ZYN001 into a state-of-the-art drug-adhesive matrix transdermal patch. Zynerba expects to begin Phase 2 clinical trials during the second half of 2017.
“We are thrilled with the progress made in our development compounds – ZYN002 and ZYN001. Additionally, we are excited with the tremendous progress made by LTS in transforming ZYN001 into an optimized transdermal patch that balances efficacy with patient convenience,” said Armando Anido, Chairman and CEO, in a press release. “We have completed the development of several prototypes which are smaller and more patient-friendly than our original design and believe that it is appropriate to move to this state of the art patch technology prior to initiating clinical development,” he said.
Fibromyalgia syndrome (FS) is a chronic disorder that causes pain throughout the body, and a diverse array of other symptoms such as fatigue, and may include cognitive (memory or thought) problems. An estimated 5.6 million patients in the U.S. are battling fibromyalgia.
Peripheral neuropathic pain also may be experienced by FS patients and is defined as pain initiated or caused by a primary lesion or dysfunction of the central or peripheral nervous systems. In patients with peripheral neuropathic pain, the pain is a symptom of another disease that has caused nerve damage —such as a herniated disc (lower back pain), diabetes (diabetic neuropathy), cancer (neuropathic cancer pain), or herpes zoster infection (postherpetic neuralgia), but is recognized as a clinical condition on its own. Approximately 14.0 million patients in the U.S. are believed to suffer from peripheral neuropathic pain.
Three Phase 2 clinical trials of ZYN002, a synthetic cannabidiol formulated as a permeation-enhanced gel for transdermal delivery, in patients with the genetic disorder Fragile X syndrome are underway. The company says it expects to report top-line results of all three Phase 2 clinical trials in the first half of 2017. In February 2016, the U.S. Food and Drug Administration (FDA) granted ZYN002 orphan-drug designation for the treatment of patients with Fragile X syndrome in the U.S.