Abstract
Background
Palliative care aims to improve the quality of life for patients with terminal illnesses by addressing physical, psychological, and social needs. However, only 14% of individuals globally who need palliative care receive it. In Pakistan, the availability is critically low, with a palliative care-to-population ratio of 1:90 million. Access to strong opioids for pain relief is severely restricted, with only 2% of terminally ill patients receiving adequate analgesia. These limitations, driven by concerns over opioid misuse and regulatory restrictions, highlight the urgent need for effective, accessible non-opioid alternatives. Suzetrigine, a novel NaV1.8 channel inhibitor, may offer a promising solution.
Methods
This brief review summarizes clinical trial data from multiple Phase 2 and Phase 3 studies evaluating the efficacy and safety of Suzetrigine in managing acute and chronic pain. Primary endpoints included the time-weighted sum of pain intensity difference over 48 hours and weekly average pain score reductions assessed using the numeric pain rating scale. The implications of these findings were contextualized in the setting of Pakistan's opioid-restricted palliative care landscape.
Results
Suzetrigine demonstrated statistically and clinically significant analgesic effects in trials involving postoperative pain, lumbar radiculopathy, and diabetic neuropathy. The drug was well-tolerated, with adverse events such as nausea, headache, and constipation being mild and infrequent.
Conclusion
Suzetrigine presents a viable non-opioid analgesic alternative for palliative care in Pakistan, where regulatory and systemic barriers limit opioid access. Its introduction could enhance pain management, reduce opioid-related harms, and support the development of a safer, more accessible palliative care model.
Introduction
Palliative care enhances the quality of life for patients with terminal illnesses and their families by addressing physical, psychological, and social challenges. Despite the global need, only 14% of the 78% of people who require palliative care globally receive such care. 1 A recent study reports the ratio of palliative care in Pakistan relative to its population as 1:90 million. 2 Furthermore, inadequately qualified personnel, resources, and mass awareness present additional challenges to its implementation. Pain, a key symptom of terminal illness, is often poorly managed. Despite international support for the use of strong opioids to manage terminal disease-associated pain, only 2% of patients with terminal diseases in Pakistan have access to such medications. 3 This restriction is often attributed to an attempt to prevent opioid abuse or misuse by classifying strong opioids like morphine and oxycodone as “controlled drugs” with limited allocation to military and tertiary care hospitals in the country. Amid this restricted and inadequate availability of opioids, Suzetrigine can serve as a potential alternative.
Understanding suzetrigine
Suzetrigine (VX-548), commercially known as Journvax, is an oral non-opioid analgesic representing the first novel pharmacological class for acute pain management in the past two decades. VX-548 is a highly selective inhibitor of voltage-gated NaV 1.8 channels. The channels expressed in peripheral sensory neurons are predominantly nociceptors, and an attractive therapeutic target for pain relief. VX-548 acts by selectively binding and stabilizing these channels in their closed state, inhibiting the transmission of pain signals to the CNS.
Suzetrigine was evaluated in two randomized, double-blind trials for acute pain management. 4 Both studies used the time-weighted sum of the pain intensity difference over 48 h (SPID48) as the primary endpoint, comparing VX-548 to a placebo. The high-dose VX-548 group showed a SPID48 improvement of 37.8 (95% CI: 9.2–66.4) after abdominoplasty and 36.8 (95% CI: 4.6–69.0) after bunionectomy. 4 As a secondary outcome, 52% of bunionectomy patients and 25% of abdominoplasty patients experienced a > 70% reduction in pain intensity within 24 h. 4
Another study evaluated Suzetrigine's efficacy in lumbar radiculopathy by assessing weekly average leg pain intensity changes on the numeric pain rating scale (NPRS) over 12 weeks. 5 Among participants, 92% also reported back pain. After two weeks, NPRS scores decreased by an average of 2.02 points, a clinically and statistically significant improvement.
A Phase 2 study on diabetic neuropathy showed promising results, with 192 patients monitored for changes in weekly average pain over 12 weeks. 6 All VX-548 treatment groups experienced statistically and clinically significant pain reduction. The pregabalin reference arm had a least square mean change of −2.09 (95% CI −2.65 to −1.52), while the high-dose VX-548 group showed a mean change of −2.26 (95% CI −2.8 to −1.70). These findings support Suzetrigine's potential as an alternative for chronic pain management. In January 2025, the FDA authorized the medication for moderate to severe acute pain following encouraging outcomes in a Phase 3 study. 7
Suzetrigine is generally well tolerated and has a superior side effect profile compared to opioids. Most adverse effects were mild to moderate, with nausea, headache, and constipation being the most common. Given the concerns about the safety profile of opioids and the side effects of NSAIDs, especially with long-term use, the introduction of a safe analgesic is beneficial, especially for the population at risk. The addiction potential of opioids is a hindrance in its commercial availability. According to data from the CDC, in 2022, 108,000 people died of drug overdose in the U.S. alone, and nearly 82,000 of those involved opioids.
Palliative care crisis in Pakistan
Pakistan's palliative care system faces challenges, including restricted access to essential pain relief medications and a severe shortage of specialized services. Despite producing substantial quantities of opium and morphine, the country's mean opioid consumption is a mere 0.05 mg per capita, starkly lower than the global average of 6.24 mg per capita. This disparity highlights the severe inadequacy of pain management resources available to patients with terminal illnesses. In a 2017 study on participants with advanced cancers, only one-third reported adequate pain relief. It also faces a significant shortfall in palliative care facilities. In 2019, only one WHO-recognized palliative care program was available in the country's largest city. The few existing palliative care services are predominantly within private sector institutions, limiting access for the broader, poorer population. The healthcare system's focus on revenue-generating treatments, such as antineoplastic therapies, often overshadows the importance of palliative care. This financial emphasis discourages palliative services, even when patients have a poor prognosis. The Pakistan Medical and Dental Council (PMDC) does not mandate palliative care education for undergraduate medical students. Similarly, the College of Physicians and Surgeons (CPSP) lacks structured training programs in this field, hindering the development of a proficient palliative care workforce.
Implications of suzetrigine for palliative care in Pakistan
In Pakistan's opioid-restricted healthcare system, Suzetrigine offers a promising alternative for sustainable and effective pain management in palliative care. Although Pakistan ranks eighth globally in opium and morphine production, it remains one of the lowest-rated countries in terms of the availability of palliative care pain relief services. Additionally, drug misuse and opioid use disorder are associated with severe social, economic, and medical consequences. In this context, non-opioid analgesics are preferable, as they do not require controlled drug regulations, making them more accessible for healthcare workers. This accessibility can significantly improve the management of severe pain in terminally ill patients and enhance the overall effectiveness of palliative care. These drugs are also considered safer for long-term use compared to opioids, as they carry a significantly lower risk of dependance, tolerance, and overdose, reducing the risk of harmful side effects and complications associated with opioid use. Additionally, reforms must be introduced in existing health policies to address the access and affordability of Suzetrigine. The introduction of Suzetrigine into Pakistan's opioid-restricted healthcare system could lead to better patient outcomes by promoting a more holistic approach to palliative care.
Footnotes
Author contributions
MM: Conceptualization, Writing - Original Draft, Supervision SK: Literature Review, Writing - Review & Editing MP: Writing - Review & Editing MB: Methodology, Investigation, Visualization MM: Writing - Review & Editing AK: Writing - Original Draft SK: Literature Review, Writing - Review & Editing SB: Methodology, Investigation, Visualization FFS: Methodology, Investigation, Visualization AN: Writing - Review & Editing, Visualization AA: Writing - Original Draft MMK: Writing - Original Draft, Supervision.
Data availability statement
This study is a review-based short communication and does not include primary data. All data supporting the findings are derived from publicly available sources, which are cited in the manuscript.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethical approval and informed consent
There are no human participants in this article and ethical approval or informed consent is not required.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
