Clinical Trials Begin in U.S. for First Cannabis-Based Medicine for Chronic Pain

By Pat Anson

The first clinical trials in the United States for a cannabis-based medicine for chronic pain are getting underway.

New York State has authorized a clinical trial of VER-01 in patients with chronic low back pain from lumbosacral radiculopathy, commonly known as sciatica. VER-01 was developed by Vertanical, a German biopharmaceutical company, and recently became available by prescription in Europe, where it is sold under the brand name Exilby.

Exilby is a full spectrum extract derived from THC, CBD and terpenes found in cannabis sativa. Unlike other cannabis-based medicines already on the market, such as Epidolex and Marinol, which are used to treat epilepsy and improve appetite, Exilby was specifically developed to treat chronic pain.

“This is an important moment for cannabis research in New York and for the future of evidence-based cannabis medicine,” John Kagia, executive director of New York Office of Cannabis Management (OCM), told The Marijuana Herald. “For decades prohibition and criminalization limited the ability of researchers to fully understand cannabis and its potential therapeutic applications.”   

Research into the pain-relieving properties of cannabis has been slow in the U.S., in large part because of marijuana’s longtime status as an illegal Schedule One controlled substance. Marijuana is now more readily available for research purposes, but there’s a lot of catching up to do with the rest of the world.

“Clinical research allows us to move beyond anecdote and evaluate cannabis-based medicines with the same rigor applied to any other therapy,” said Nakesha Abel, PhD, Director of Scientific Programs & Research Health & Scientific Affairs at OCM.

Vertanical has also begun recruiting patients in Texas for a Phase Three clinical trial of VER-01 with 810 participants. Researchers are looking for patients with chronic painful lumbosacral radiculopathy who have previously used non-opioid analgesics that were not sufficient for pain relief or caused unwanted side effects. 

In studies already completed in Europe, VER-01 provided better pain relief to patients with chronic low back pain in a head-to-head comparison with low doses of opioids. Vertanical is also studying VER-01 as a treatment for osteoarthritis and painful diabetic peripheral neuropathy 

Exilby became available in Germany and Austria in September, with approval in the United Kingdom expected by the end of the year.

In March, VER-01 received a Breakthrough Therapy designation from the FDA, which will speed up its development and review in the U.S. But even with “breakthrough” status, a new drug application for VER-01 to the FDA is not expected until 2028.  

More Lackluster Results for Non-Opioid Pain Reliever

By Pat Anson

New questions are being raised about the effectiveness of an experimental non-opioid analgesic and whether it can be a viable alternative to opioid pain medication.

Results from Vertex Pharmaceuticals’ Phase 2 clinical trial show that suzetrigine is essentially no more effective than a placebo in relieving back and hip pain caused by lumbosacral radiculopathy (LSR).

After 12 weeks of treatment with the drug suzetrigine, patients with LSR had a 2.02 average reduction in their pain scores on a rating scale of zero to 10. That compares to an average reduction of 1.98 for patients who received a placebo or sham treatment.

Although the difference between 2.02 and 1.98 is minuscule, Vertex claimed the overall findings were “statistically significant and clinically meaningful” in a press release. The company blamed the lackluster results on the placebo effect and the difficulty of treating lumbosacral radiculopathy.

“Suzetrigine has again demonstrated its potential to fill an important unmet need in the treatment of pain,” said Carmen Bozic, MD, Executive Vice President and Chief Medical Officer at Vertex. “We did not see separation between the suzetrigine and the placebo arms. Yet our post-hoc analyses suggest that this could be due to the high placebo response in this study.”

Despite the disappointing results, Vertex still plans to go ahead with a Phase 3 study of suzetrigine for LSR, while changing the study design to minimize the impact of the placebo.

“Managing the placebo response in pain trials is a complex challenge. We look forward to innovating in clinical trial design, including for the pivotal study, with the aim of bringing a potentially safe and effective treatment to patients suffering from LSR," said Christine Sang, MD, co-chair of Vertex’s Peripheral Neuropathic Pain steering committee and principal investigator of the study.

Suzetrigine is already under consideration by the FDA as a treatment for acute pain, with a decision expected in late January. If approved, suzetrigine would be the first new medication for acute pain in over two decades.

Unlike opioids, suzetrigine blocks pain signals in the peripheral nervous system before they reach the brain. That means it won’t have the “liking” effect that opioids can have in some patients or be as addictive.

Although suzetrigine has been touted as a novel painkiller that "could bring relief to millions” without the risk of addiction, findings from earlier studies have also been mixed. In a Phase 3 trial of patients recovering from minimally invasive surgery, suzetrigine was no more effective than a low dose combination of hydrocodone and acetaminophen, more commonly known as Vicodin.

Although Vertex downplayed the results from the Phase 2 study, shares of the company lost about 15% of their value after last week’s announcement. Wall Street analysts said the Phase 2 findings were “very messy” and "raise considerable risk around suzetrigine's potential.”

Ultimately, it will be up to the FDA to decide whether suzetrigine should be allowed on the market. The agency is under pressure to approve new non-opioid analgesics, so it may look past the disappointing clinical trial findings. If approval is granted in January, it will coincide with implementation of the NOPAIN Act, which will make non-opioid analgesics in outpatient surgical settings eligible for higher Medicare reimbursement rates.  

In addition to acute pain and lumbosacral radiculopathy, Vertex is also studying suzetrigine as a treatment for diabetic peripheral neuropathy.