The arsenal of medications for pain treatment has just expanded in the United States. In a country plagued for years by the opioid crisis, the recent approval by the regulatory agency FDA of suzetrigine (marketed as Journavx by Vertex Laboratories) has generated great anticipation as a safer alternative to these drugs and, for now, without suspicion of addictive potential.
The new oral medication has been approved for the treatment of acute pain of any kind, from moderate to severe. It is the first innovation in analgesia in 20 years. Suzetrigine is a medication, the first of its kind, a selective inhibitor of the sodium channel NaV1.8. It acts on this signaling pathway of the peripheral nervous system, preventing pain sensations from reaching the brain.
In reality, the drug blocks sodium channels similarly to local anesthetics, such as lidocaine. However, by specifically acting on the pain-transmitting neurons, it only relieves painful stimuli and avoids side effects, as it does not affect other sensations like pressure or touch, explains Carlos Goicoechea, Professor of Pharmacology at King Juan Carlos University and Vice President of the Spanish Pain Society (SED).
The pharmacologist illustrates the difference between suzetrigine and lidocaine with the typical effect of this anesthetic administered in a dentist's office. After a dental procedure, he recalls, it is common for the patient to bite their tongue because they cannot feel it: "Not only does it block the painful stimulus but also other types of stimuli, which does not happen with this medication," he points out.
How does this new pain medication work?
The specific mechanism of action of suzetrigine allows for oral administration, clarifies Goicoechea. "Lidocaine needs to be used parenterally, through an injection near the nerve to be anesthetized, as otherwise it can produce more general effects. Suzetrigine, as it only acts on pain neurons, does not affect other nerve transmissions. This makes it, at least in theory, a very interesting and innovative drug."
According to the SED spokesperson, its mechanism of action allows him to anticipate that the drug will be safe, and significant central side effects would not be expected. He indicates that it "acts peripherally, like other well-known drugs such as ibuprofen, but instead of acting on the pain focus, it intervenes in the transmission of painful information and reduces the amount of pain-related information that reaches the brain."
What do the clinical trials, on which the FDA based its approval, say?
The FDA's approval of suzetrigine is supported by two double-blind, randomized, placebo-controlled clinical trials in surgically operated patients who had undergone abdominoplasty or bunionectomy (bunion removal or toe realignment). All participants were allowed to use ibuprofen as a rescue analgesic. The results showed a statistically significant reduction in pain with the active treatment.
Regarding safety, the drug was associated with itching, rash, muscle spasms, and an increase in blood creatine phosphokinase levels. Concomitant use with potent CYP3A inhibitors is contraindicated, and patients should avoid grapefruit-containing foods or beverages while taking the drug.
Why is it a safer alternative to current opioids?
Suzetrigine stands out for its potency, but above all, in comparison with opioids, for its safety, highlights Agustín Mendiola, Coordinator of the Pain Unit at Puerta de Hierro Hospital and Vice President of the Pain Section of the Spanish Society of Anesthesiology, Resuscitation, and Pain Therapy (Sedar). "The main difference lies in the side effects associated with opioids. These can cause severe constipation, drowsiness, dependence, dizziness, and mobility disorders, especially in older patients. In contrast, these effects have not been reported with suzetrigine."
Due to its efficacy and safety attributes, Mendiola explains that in terms of analgesic potency, the drug would be placed in the third tier of the WHO analgesic ladder, at the same level as potent opioids; but due to its side effect profile, it could be placed in the second tier, along with weak opioids like tramadol and codeine.
The potential arrival of this drug in Spain would be very welcome, agree the experts, but Mendiola warns that its cost could limit its use. Despite the drawbacks of opioids, the Sedar expert points out that they are cost-effective drugs, whereas it is likely that if the drug is launched in Spain, it will come with a high price tag, "so it is probable that, in Spain, its use will be limited to patients intolerant or allergic to opioids, without reaching widespread application."
Suzetrigine represents a paradigm shift in the management of acute pain, but the company is confident that its potential market will be much larger with future approvals for chronic and neuropathic pain. Currently, it is being investigated in phase III for peripheral diabetic neuropathy, and the company announced in December positive results from a phase II study in painful lumbosacral radiculopathy, one of the most common causes of peripheral neuropathic pain.