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iStock, hapabapa BMO Capital Markets analyst Evan Seigerman in a note to investors said the late-stage data for Vertex’s experimental non-opioid pain medication “reaffirms our confidence in the strength of suzetrigine’s profile.” However, William Blair analysts view these data as “an incremental positive” as the company faces challenges in targeting the acute pain market. Vertex Pharmaceuticals ’ investigational non-opioid pain therapy suzetrigine has a cleaner safety profile than standard pain relief medicines and even placebo, according to full Phase III data presented over the weekend at the 2024 annual meeting of the American Society of Anesthesiologists in Philadelphia. In study participants who were undergoing abdominoplasty—more commonly known as a tummy tuck—adverse events of any severity arose in 50% of patients given suzetrigine. By comparison, toxicities were detected in 60.7% of patients managed with hydrocodone bitartrate/acetaminophen (HB/APAP) and in 56.3% of placebo comparators. Suzetrigine continued to have a better safety pro HB/APAP and placebo even after disaggregating according to severity. Severe toxicities developed in 1.8% of abdominoplasty patients in the suzetrigine arm, versus 2% and 2.7% in HB/APAP and placebo counterparts, respectively. One patient in the placebo arm died. Similar safety findings were observed in patients who underwent bunionectomy, which is a surgical procedure to correct a bone deformity in the toes. Aside from the positive safety data, Vertex also reported an efficacy update for suzetrigine at ASA 2024. In abdominoplasty patients, suzetrigine monotherapy led to a 48.4-point improvement in pain scores, as measured by SPID48, a tool that measures time-weighted pain intensity from 0 to 48 hours after surgery. This effect was statistically significant, with a p-value less than 0.0001, according to Vertex’s presentation. While suzetrigine’s effect seems to be weaker in bunionectomy patients, it still remained significantly better than placebo. Mean SPID48 scores were 29.3 points higher after suzetrigine treatment versus placebo. Compared with the HB/APAP combo, however, suzetrigine monotherapy did not lead to significantly better pain relief. Mean SPID48 scores improved by only 6.6 points in abdominoplasty patients versus HB/APAP, an effect that fell short of significance. Meanwhile, in bunionectomy patients, mean SPID48 scores appear to have worsened by 20.2 points in the suzetrigine arm, which was statistically significant. Suzetrigine is an orally available pain signal inhibitor that works by targeting and binding to the NaV1.8 voltage-gated sodium channel. Typically found on pain-sensing neurons, these channels help transmit pain signals from the peripheral nervous system back to the spine and brain. NaV1.8 channels are validated pain targets. In July 2024, the FDA accepted Vertex’s New Drug Application for suzetrigine for moderate to severe acute pain, with a target action date on Jan. 30, 2025 . If approved, suzetrigine could provide patients with an effective non-opioid option for pain relief. BMO Capital Markets analyst Evan Seigerman in a note to investors said the detailed late-stage data for Vertex’s non-opioid pain medication “reaffirms our confidence in the strength of suzetrigine’s pro acute pain.” However, William Blair analysts in a note to investors said they view Vertex’s presentation at ASA 2024 as “an incremental positive” for suzetrigine with some challenges as the company targets the acute pain market. “In the post-surgical outpatient setting, we continue to believe suzetrigine has a strong argument for inclusion in the market but note that pricing remains a point of investor contention along with how this impacts reimbursement, formulary placement, and prior authorization requirements, the latter of which Vertex is keen to avoid,” the analysts wrote. Truist Securities analyst Joon Lee in a note said his firm is “not entirely sold yet on the commercial case for suzetrigine in acute pain,” adding that “if there is indeed will to use non-opioid analgesic, we think there are numerous options that are readily available that will be significantly cheaper than suzetrigine.”

The increasing cases of peripheral neuropathic pain, rise in screening for diabetic neuropathic pain among diabetics, increase in the geriatric population, and launch of new approved drugs, among other reasons are likely to fuel the growth of the peripheral neuropathic pain market size during the forecast period (2024–2034). LAS VEGAS, Aug. 28, 2024 /PRNewswire/ --DelveInsight's Peripheral Neuropathic Pain Market Insights report includes a comprehensive understanding of current treatment practices, peripheral neuropathic pain emerging drugs, market share of individual therapies, and current and forecasted market size from 2020 to 2034, segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan]. Key Takeaways from the Peripheral Neuropathic Pain Market Report According to DelveInsight's analysis, the market size for peripheral neuropathic pain was found to be ~ USD 12 billion in the 7MM in 2023. The United States accounts for the largest market size of PNP in comparison to EU4 (Germany, Spain, Italy, France), the United Kingdom, and Japan. The total cases of peripheral neuropathic pain in the 7MM were approximately 60 million cases in 2023, which are expected to increase during the study period (2020–2034). Leading peripheral neuropathic pain companies such as Lexicon Pharmaceuticals, Merz Therapeutics, Apurano Pharmaceuticals, Vertex Pharmaceuticals, WEX Pharmaceuticals, Scilex Holding Company, and others are developing novel peripheral neuropathic pain drugs that can be available in the peripheral neuropathic pain market in the coming years. The promising peripheral neuropathic pain therapies in the pipeline include LX9211, XEOMIN (incobotulinumtoxinA), Adezunap (AP707), Suzetrigine (VX-548), HALNEURON (Tetrodotoxin or TTX), SEMDEXA (SP-102), and others. Compared to all the emerging therapies, LX9211 and SEMDEXA are expected to become the market leader, having a major influence on the peripheral neuropathic pain market of the 7MM by 2034. In November 2023, Lexicon Pharmaceuticals announced that it has enrolled the first patient in PROGRESS (A Phase IIb, dose-ranging, randomized, double-blind, placebo-controlled, parallel-group, multicenter study with an open-label extension in patients with diabetic peripheral neuropathic pain) studying LX9211. Discover which therapies are expected to grab the major peripheral neuropathic pain market share @ Peripheral Neuropathic Pain Market Report Peripheral Neuropathic Pain Overview Peripheral neuropathies refer to conditions affecting peripheral nerve cells and fibers, arising from a variety of underlying causes. These nerves include the cranial nerves, spinal nerve roots and ganglia, nerve trunks and divisions, and the autonomic nervous system nerves. Peripheral neuropathies can be classified in several ways, such as mononeuropathies, multifocal neuropathies, and polyneuropathies. Mononeuropathy involves damage to a single nerve, while multiple mononeuropathy affects two or more nerves in different locations. Polyneuropathy typically impacts many or most nerves. The diversity of symptoms associated with peripheral neuropathy allows for the identification of distinct clinical phenotypes, which is important for guiding the diagnostic process. Nerve conduction studies are crucial for determining the phenotype and assessing severity. Additional diagnostic tools, such as laboratory tests, genetic testing, cerebrospinal fluid examination, nerve imaging, and nerve biopsy, may be useful in specific clinical situations. Peripheral Neuropathic Pain Epidemiology Segmentation The peripheral neuropathic pain epidemiology section provides insights into the historical and current peripheral neuropathic pain patient pool and forecasted trends for the 7MM. It helps recognize the causes of current and forecasted patient trends by exploring numerous studies and views of key opinion leaders. The peripheral neuropathic pain market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Total Cases of PNP Type-specific Cases of PNP Treated Cases of PNP Peripheral Neuropathic Pain Treatment Market The treatment of peripheral neuropathic pain depends on the underlying cause and the severity of symptoms. Initial management typically involves conservative measures, including medications such as NSAIDs, acetaminophen, and, in more severe cases, opioids. For radicular symptoms, neuroleptic agents may be used, and systemic steroids are sometimes prescribed for acute low back pain. Nonpharmacological treatments like physical therapy, acupuncture, chiropractic manipulation, and traction are also employed, though their effectiveness is debated. Interventional procedures, such as epidural steroid injections and percutaneous disc decompression, are commonly performed, while surgical options like decompression and spinal fusion are considered for cases that do not respond to other treatments. Pain management for PNP also includes the use of drugs such as NSAIDs, anticonvulsants, and antidepressants, with specific medications like QUTENZA, NUCYNTA ER, and TARLIGE approved for certain patient groups. TARLIGE (mirogabalin besylate) is an oral gabapentinoid developed by Daiichi Sankyo to treat peripheral neuropathic pain (PNP), including diabetic PNP and postherpetic neuralgia. In January 2019, Daiichi Sankyo announced that TARLIGE received approval for marketing in Japan for PNP treatment, offering patients in Japan a new therapeutic option for managing PNP. NUCYNTA ER (tapentadol) is an opioid agonist available as an extended-release film-coated tablet for oral use. It is prescribed for managing neuropathic pain related to diabetic peripheral neuropathy (DPN). In August 2012, the US FDA approved a sNDA for NUCYNTA ER, allowing it to be used as an oral analgesic taken twice daily to manage neuropathic pain in adults with DPN when ongoing, around-the-clock opioid treatment is required for a prolonged duration. The QUTENZA (capsaicin) 8% topical system delivers capsaicin through a localized dermal application. Capsaicin acts as an agonist for the TRPV1 receptor. In July 2020, Grünenthal's US subsidiary, Averitas Pharma, obtained FDA approval for the QUTENZA 8% patch to treat neuropathic pain related to diabetic peripheral neuropathy in the feet of adults. To know more about peripheral neuropathic pain treatment guidelines, visit @ Peripheral Neuropathic Pain Management Peripheral Neuropathic Pain Pipeline Therapies and Key Companies LX9211: Lexicon Pharmaceuticals XEOMIN (IncobotulinumtoxinA): Merz Therapeutics Adezunap (AP707): Apurano Pharmaceuticals Suzetrigine (VX-548): Vertex Pharmaceuticals HALNEURON (Tetrodotoxin or TTX): WEX Pharmaceuticals SEMDEXA (SP-102): Scilex Holding Company Discover more about peripheral neuropathic pain drugs in development @ Peripheral Neuropathic Pain Clinical Trials Peripheral Neuropathic Pain Market Dynamics The peripheral neuropathic pain market dynamics are expected to change in the coming years. Emerging disease-modifying therapies for diabetic neuropathy, CIPN, and LSR are gaining attention due to the growing prevalence of cancer, increased chemotherapy usage, and the large patient pool in need of pain management. The lack of disease-modifying treatment options in the current landscape, which relies solely on symptomatic relief, highlights the market potential for these therapies. Recent developmental activities targeting novel pathways, such as adapter-associated kinase 1 (AAK1) and the Nav1.8 voltage-gated sodium channel, aim to provide opioid-free pain relief, which could lead to a high uptake and the ability to charge a premium price. Furthermore, potential therapies are being investigated for the treatment of peripheral neuropathic pain, and it is safe to predict that the treatment space will significantly impact the peripheral neuropathic pain market during the forecast period. Moreover, the anticipated introduction of emerging therapies with improved efficacy and a further improvement in the diagnosis rate are expected to drive the growth of the peripheral neuropathic pain market in the 7MM. However several factors may impede the growth of the peripheral neuropathic pain market. The management of DPN is challenging due to the persistent and severe nature of neuropathic pain, which is frequently ineffectively treated and negatively impacts the quality of life, further complicated by pharmacogenetic and genetic variations in patients; additionally, while improving glycemic control in Type-2 diabetes remains uncertain, the availability of low-cost generics in the treatment landscape may significantly hamper the uptake of emerging therapies, increasing the burden and associated health costs. Moreover, peripheral neuropathic pain treatment poses a significant economic burden and disrupts patients' overall well-being and QOL. Furthermore, peripheral neuropathic pain market growth may be offset by failures and discontinuation of emerging therapies, unaffordable pricing, market access and reimbursement issues, and a shortage of healthcare specialists. In addition, the undiagnosed, unreported cases and the unawareness about the disease may also impact peripheral neuropathic pain market growth. Scope of the Peripheral Neuropathic Pain Market Report Therapeutic Assessment: Peripheral Neuropathic Pain current marketed and emerging therapies Peripheral Neuropathic Pain Market Dynamics: Key Market Forecast Assumptions of Emerging Peripheral Neuropathic Pain Drugs and Market Outlook Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, Peripheral Neuropathic Pain Market Access and Reimbursement Download the report to understand which factors are driving peripheral neuropathic pain market trends @ Peripheral Neuropathic Pain Market Trends Table of Contents Related Reports Peripheral Neuropathic Pain Epidemiology Forecast Peripheral Neuropathic Pain Epidemiology Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology as well as the Peripheral Neuropathic Pain epidemiology trends. Peripheral Neuropathic Pain Pipeline Peripheral Neuropathic Pain Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Peripheral Neuropathic Pain companies, including Haisco Pharmaceutical Group, GlaxoSmithKline, Algiax Pharmaceuticals, Apurano Pharmaceuticals GmbH, Eli Lilly and Company, Shanghai SIMR Biotechnology, Lexicon Pharmaceuticals, among others. Diabetic Neuropathy Market Diabetic Neuropathy Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key diabetic neuropathy companies, including Novo Nordisk, Ionis Pharmaceuticals, Pfizer, Regeneron, NeuroMetrix, among others. Diabetic Neuropathy Pipeline Diabetic Neuropathy Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key diabetic neuropathy companies, including Goldfinch Bio, Novartis, Serodus, CURACLE, Daiichi Sankyo, NeuroBo Pharmaceuticals, Dong-A Pharmaceutical , among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP

Pictured: Rows of white pill bottles on a white surface/iStock, Androlia With the opioid epidemic continuing to ravage the U.S., Vertex's announcement Tuesday that its non-opioid pain treatment VX-548 led to “significant improvement” in pain in two Phase III trials was widely hailed as a breakthrough. But the investigational drug did miss the first key secondary endpoint: superiority to a combination of the opioid hydrocodone bitartrate and Tylenol—a duo branded as Vicodin. This raises the question: Is it possible to do better? Both trials—one testing VX-548 following abdominoplasty (tummy tuck) surgery, the other following bunionectomy surgery—hit the primary endpoint of statistically significant reduction of pain intensity from 0 to 48 hours. VX-548 failed, however, to beat Vicodin on the same scale. During an investor call Tuesday, analysts also questioned the drug’s performance on another key secondary endpoint: median time to pain relief. In both indications, VX-548 had a “more rapid onset to meaningful pain relief” than placebo, Vertex reported, with median time to pain relief being two hours in tummy tuck patients and four hours in bunionectomy patients versus eight hours for the placebo group. Analysts on the call also appeared to be seeking faster time to pain relief, with Leerink Partners’ David Risinger asking if Vertex’s Phase I NaV1.8 inhibitors may offer a quicker onset. Vertex CEO Reshma Kewalramani responded, saying, “If it is possible to get even better than VX-548, we are determined to be the ones who do so.” Stuart Arbuckle, the company’s chief operating officer, also responded to questions from analysts, including how payors would respond to the drug’s efficacy. The “significant adverse events” and addictive potential associated with opioids are a major deterrent, he noted, adding that he believes payors will “warmly welcome the advent of a truly non-opioid pain med as this compelling combination of efficacy and safety and tolerability.” When pressed for further details on the missed endpoint, Vertex representatives directed BioSpace to the investor call. The Second Generation VX-548 is a novel NaV1.8 pain signal inhibitor with a rich history. “The mechanistic evidence for [NaV1.8], even in the year 2001, was crystal clear,” said Stephen Waxman, a professor of neurology at Yale School of Medicine. “If you could shut it off, you had a good chance of attenuating pain.” This is around the time Vertex began its efforts against NaV1.8, which would ultimately yield VX-548, Waxman said. Waxman, whose work contributed to the revelation that the NaV1.7, NaV1.8 and NaV1.9 sodium channels played a central role in pain signaling, highlighted three possible reasons for VX-548’s failure to beat Vicodin. “One possibility is that [Vertex] did a good job on dosing but didn’t get it precisely right,” he said. “There could have been a higher dose with higher efficacy.” A second possibility, he said, is that a second-generation drug “will have more potency, more effective distribution, fewer side effects, be able to be dosed better and give better efficacy.” Lastly, Waxman suggested that NaV1.8 may be “important enough in pain signaling that you get this degree of reduction of pain when it is blocked, but there is some redundancy in the pain pathway, so block of NaV1.8 reduces pain but does not totally abolish it.” He likened VX-548 to the early days of the statin drugs. “The very first statin drugs worked, but in retrospect, they were not optimal, and the real bang for the buck in terms of societal impact was in the second and third-generation drugs,” he said. “And that’s where I think we are right now.” As for what a second-generation drug might look like, Waxman noted that there are many approaches to targeting NaV1.8, including small-molecule blockers, peptide blockers, toxin derivatives, antibodies, knockdown therapies and gene therapy approaches. “Now that we know that [NaV1.8] is a druggable target and we know that blocking it reduces pain, we have proof of concept in humans,” Waxman said. “That raises the exciting question of whether there are there other ways to attack 1.8, and there undoubtedly are. It is a very exciting time in the search for new, non-addictive pain medications.” Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Also follow her on LinkedIn.