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FDA Fast Tracks New Injection for Morton's Neuroma

November 18, 2016
The US Food and Drug Administration (FDA) has fast-tracked a novel, nonopioid injection therapy for Morton's neuroma, a painful nerve condition that currently lacks any FDA-approved therapies.

Interview with James Campbell, MD

The US Food and Drug Administration (FDA) has granted a Fast Track designation to a new treatment for Morton’s neuroma, a nerve disorder in the foot that can cause serious neuropathic pain.

Currently referred to as CNTX-4975, this prospective nonopioid drug is under manufacture by Centrexion Therapeutics. According to the company, the drug has completed a successful Phase 2b study and a Phase 3 clinical trial is forthcoming over the next year.

“Morton’s neuroma is a really an interesting condition in that there really is no FDA-approved treatment,” James Campbell, MD, founder, president, and chief scientific officer of Centrexion, told Practical Pain Management.

Designed to be the first-ever patented form of synthetic capsaicin (a derivative of the chili plant), CNTX-4975 is described as a “potent” and “ultrapure” trans-capsaicin agent that doctors will be able to inject directly into the foot at the site of the neuroma.1

What is Morton’s neuroma?

Morton’s neuroma occurs when the tissue surrounding one of the nerves in the foot thickens. Patients typically report feeling as if a pebble is stuck in their shoe. A burning pain in the ball of the foot can emerge, especially when the ball of the foot is put under strain, such as when walking, running, or wearing high-heeled shoes. Burning, tingling, and numbness in the toes is also common with the condition.

Doctors commonly see the condition in adult women, who can experience Morton’s neuroma from wearing high heels or long-distance running. The condition can vary in seriousness. While some can find alleviation of the pain simply by wearing lower-heeled shoes or orthotics, many patients can find the pain disabling and require medical intervention.

An Analgesic Derived from Chilies

Capsaicin is the active component found in chili peppers and for years has been a useful nociceptive agent for studying pain in humans. “Unlike a lot of other pain stimulators where there is a liability of tissue injury,” capsaicin-induced pain fades after a few days with no apparent injury, Dr. Campbell said.

This occurs through the transient receptor potential cation channel subfamily V member 1 (TrpV1), which colloquially referred to as the capsaicin receptor. “This receptor is selectively expressed on pain fibers, and when it’s over-activated as with capsaicin, the pain terminal is deactivated for long periods of time,” Dr. Campbell said.

Doctors now are working to exploit this analgesic effect to work as a “molecular scalpel,” by cutting out the pain, not cutting out the nerve.

Even though doctors have been aware of Morton’s neuroma for decades,2 current standards of care include surgical removal of the affected nerve, which results in complete loss of function of the nerve, causing numbness in the affected area. Despite the seriousness of this intervention, some data suggests resection of the nerve has a varied rate of success in treating the condition.3

Other treatments have emerged over the years as possible interventions for Morton’s neuroma, including ultrasound-guided alcohol sclerosing injections, as well as radio-frequency ablation and cryoablation therapy.4-8 However, like surgical interventions, these treatments also appear to have a varied rate of success and similarly rely on destroying the peripheral nerve to counteract the symptoms.

Other existing therapies for Morton’s neuroma present their own problems, as well. While doctors may prescribe nonsteroidal anti-inflammatory drugs (NSAIDs) to patients suffering from Morton’s neuroma, the risk of toxicity is a relevant issue. Also, opioid medications prescribed to treat Morton’s neuroma can place patients at risk of dependence, addiction, and overdose.

A Hopeful Alternative to Invasive Interventions

According to Centrexion, CNTX-4975 works differently by specifically targeting the capsaicin receptor (TRPV1) in order to inactivate the local pain fibers transmitting stimuli to the brain. However, unlike other therapies, the injection is less invasive. The nerve is not permanently damaged by the procedure.

In a Phase 2b randomized, double-blind, placebo-controlled, parallel group, single-injection study, researchers found positive results from the initial injection given to patients suffering from Morton’s neuroma. Patients experienced rapid analgesia with no loss of sensation in their toes.

Granted, pain at injection is an expected side effect of the procedure, and the level of pain that patients experience can vary widely. “But we also noticed that even with placebo, there is a range of pain responses going to the extremes. So we have been working on dealing with the procedure discomfort, and we’ve identified some local procedures that can be instituted that contain the procedure pain. So at the end of the day, the patient comes away from this saying the procedure pain is tolerable,” Dr. Campbell noted.

Patients typically feel the side effect subside after a half hour to an hour after injection with some lingering discomfort 24 to 48 hours after the injection. However, after getting through the initial discomfort of the procedure, patients experience long-lasting analgesic benefit from the single injection.

“One of the things we need to get more information about is the durability of the effect.” Since patient outcomes from the first phase 2b trial showed the analgesic benefits of the treatment did not fade at all after 12 weeks, the company still is determining how long an analgesic benefit patients can expect to experience, Dr. Campbell told Practical Pain Management.

Also, CNTX-4975 is a non-opioid treatment, so it avoids the risks commonly associated with opioid medications. Because the drug is cleared from the body within 24 hours of injection, the risks of toxicity are significantly better compared to taking NSAIDs, according to the company.

“Our reason for being excited about this condition is that we are looking at the prospects of addressing the pain without interfering with the other aspects of the nerve function,” Dr. Campbell told Practical Pain Management.

The FDA’s Fast Track designation facilitates a more expedited review process of prospective drugs so they can reach drug approval more quickly. The Fast Track designation is typically awarded to prospective drugs used to treat serious conditions or to interventions that can meet a significant, unmet medical need in the population.

The drug is also being considered as a possible site-injection treatment for chronic moderate to severe pain from knee osteoarthritis (OA), with a Phase 2b study currently in process. A double-blind trial in pet dogs is also in progress. The company has not announced an expected timeframe for releasing the drug to market, although it plans to begin Phase 3 research sometime in next year.

“We are committed to beginning the Phase 3 program over the next year. This is a high priority for the company and we are very excited about this product,” said Dr. Campbell.

Last updated on: November 18, 2016
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