A Phase 3, Open-label Study Evaluating the Long-term Safety and Effectiveness of Suzetrigine in Subjects With Pain Associated With Diabetic Peripheral Neuropathy

The purpose of this study is to evaluate the long-term safety and tolerability of SUZ and long-term effectiveness of SUZ in treating pain associated with DPN.

Start Date01 Dec 2024

Sponsor / Collaborator

Vertex Pharmaceuticals, Inc.

NCT06628908 / RecruitingPhase 3

A Phase 3, Randomized, Double-blind, Placebo- and Active-Controlled Study of the Efficacy and Safety of Suzetrigine in Subjects With Pain Associated With Diabetic Peripheral Neuropathy

The purpose of this study is to evaluate the efficacy, safety, and tolerability of Suzetrigine (SUZ) in participants with pain associated with diabetic peripheral neuropathy (DPN).

Start Date01 Oct 2024

Sponsor / Collaborator

Vertex Pharmaceuticals, Inc.

NCT06420765 / CompletedPhase 1

A Phase 1, Randomized, Double-blind, Placebo-controlled, Parallel Study Evaluating the Effects of Single Doses of NaV1.8 Inhibitors on C-Nociceptor Action Potentials in Healthy Adults

The purpose of this study is to determine the effects of Nav1.8 inhibition on activity-dependent slowing (ADS) of C-nociceptor nerve fibers, evoked action potential (AP) conduction velocity of C-nociceptor nerve fibers using VX-150 and VX-548.

Start Date21 May 2024

Sponsor / Collaborator

Vertex Pharmaceuticals, Inc.

100 Clinical Results associated with Suzetrigine

100 Translational Medicine associated with Suzetrigine

100 Patents (Medical) associated with Suzetrigine

Literatures (Medical) associated with Suzetrigine

01 Dec 2024·MOLECULAR PHARMACOLOGY

State-Dependent Inhibition of Nav1.8 Sodium Channels by VX-150 and VX-548

Article

Author: Fujita, Akie ; Zhang, Han-Xiong Bear ; Ma, Xiao ; Vaelli, Patric ; Osorno, Tomás ; Jo, Sooyeon ; Bean, Bruce P. ; Bean, Bruce P

Nav1.8 sodium channels (Nav1.8) are an attractive therapeutic target for pain because they are prominent in primary pain-sensing neurons with little expression in most other kinds of neurons. Recently, two Nav1.8-targeted compounds, VX-150 and VX-548, have shown efficacy in clinical trials for reducing pain. We examined the characteristics of Nav1.8 inhibition by these compounds. The active metabolite form of VX-150 (VX-150m) inhibited human Nav1.8 channels with an IC₅₀ of 15 nM. VX-548 (suzetrigine) was even more potent (IC₅₀ 0.27 nM). Both VX-150m and VX-548 had the unusual property of "reverse use-dependence," whereby inhibition could be relieved by repetitive depolarizations, a property seen before with another Nav1.8 inhibitor, A-887826. The relief of VX-548 inhibition by large depolarizations occurred with a time constant of ∼40 milliseconds that was not concentration-dependent. Reinhibition at negative voltages occurred with a rate that was nearly proportional to drug concentration, consistent with the idea that relief of inhibition reflects dissociation of drug from the channel and reinhibition reflects rebinding. The relief of inhibition by depolarization suggests a remarkably strong and unusual state-dependence for both VX-150m and VX-548, with very weak binding to channels with fully activated voltage sensors despite very tight binding to channels with voltage sensors in the resting state. SIGNIFICANCE STATEMENT: The Nav1.8 sodium channel (Nav1.8) is a current target for new drugs for pain. This work describes the potency, selectivity, and state-dependent characteristics of inhibition of Nav1.8 channels by VX-150 and VX-548, compounds that have recently shown efficacy for relief of pain in clinical trials but whose mechanism of interaction with channels has not been described. The results show that the compounds share an unusual property whereby inhibition is relieved by depolarization, demonstrating a state-dependence different from most sodium channel inhibitors.

01 Dec 2024·CURRENT OPINION IN CHEMICAL BIOLOGY

Drug discovery targeting Nav1.8: Structural insights and therapeutic potential

Review

Author: Yan, Nieng ; Huang, Jian ; Wang, Huan ; Jin, Xueqin ; Zang, Jie

Voltage-gated sodium (Na_v) channels are crucial in transmitting action potentials in neurons. The tetrodotoxin-resistant subtype Na_v1.8 is predominantly expressed in the peripheral nervous system, offering a unique opportunity to design selective inhibitors for pain relief. A number of compounds have been reported to specifically block Na_v1.8. Among these, VX-548 is already in regulatory review for the treatment of moderate-to-severe acute pain and holds the promise to be the first non-opioid pain killer over the past twenty years. Recent structural studies using cryogenic electron microscopy (cryo-EM) and structure-based predictive modeling have provided unprecedented insights into the structural pharmacology of Na_v1.8. In this review, we summarize the latest developments in Na_v1.8-selective inhibitors, focusing on the druggable sites and mechanisms that confer subtype specificity. These structural insights highlight the potential for Na_v1.8 inhibitors to deliver non-addictive pain management, thus illuminating the avenue to next-generation analgesic development.

01 Nov 2024·Current Pain and Headache Reports

Frontiers in Acute Pain Management: Emerging Concepts in Pain Pathways and the Role of VX-548 as a Novel NaV1.8 Inhibitor: A Narrative Review

Review

Author: Varrassi, Giustino ; Lehuquet, Arianna M ; Baptiste, Carlo Jean ; Everett, Erin S ; Ahmadzadeh, Shahab ; Kaye, Alan D ; Shekoohi, Sahar ; Plessala, Michael J ; Barrie, Sonnah ; Mychaskiw, George ; Mason, Joseph W ; Maitski, Rebecca

PURPOSE OF REVIEW:

Despite ongoing research into alternative postsurgical pain treatments, opioids remain widely used analgesics regardless of associated adverse effects, including dependence and overdose, as demonstrated throughout the current opioid crisis. This is likely related to a failure in proving the efficacy of alternative analgesics in clinical trials, despite strong evidence supporting the potential for effective analgesia through in vitro studies. While NaV1.7 and NaV1.8 channels have shown to be key components of pain perception, studies regarding pharmacological agents utilizing these channels as targets have largely failed to demonstrate the efficacy of these proposed analgesics when compared to current multimodal pain treatment regimens.

RECENT FINDINGS:

However, the novel NaV1.8 channel inhibitor, VX-548 has surpassed previously studied NaV1.8 inhibitors in clinical trials and continues to hold promise of a novel efficacious analgesic to potentially be utilized in multimodal pain treatment on postsurgical patients. Additionally, NaV1.8 is encoded by the SCN10A, which has been shown to be minimally expressed in the brain, suggesting a lower likelihood of adverse effects in the CNS, including dependence and abuse. Novel pharmacologic analgesics that are efficacious without the significant side effects associated with opioids have lacked meaningful development. However, recent clinical trials have shown promising results in the safety and efficacy of the pharmacological agent VX-548. Still, more clinical trials directly comparing the efficacy of VX-548 to standard of care post-surgical drugs, including opioids like morphine and hydromorphone are needed to demonstrate the long-term viability of the agent replacing current opioids with an unfavorable side effect profile.

News (Medical) associated with Suzetrigine

20 Dec 2024

·www.globenewswire.com

Channel Therapeutics Highlights Differences Between NaV1.7 and NaV1.8 in Light of Recent Clinical Data on Suzetrigine

FREEHOLD, N.J., Dec. 20, 2024 (GLOBE NEWSWIRE) -- Channel Therapeutics Corporation, (“Channel” or the “Company”), (NYSE American: CHRO), a pioneer in the development of non-opioid pain treatment therapeutics, is providing a statement regarding Vertex Pharmaceutical’s recently announced Phase 2 data of Suzetrigine, an investigational, oral, highly selective NaV1.8 pain signal inhibitor in people with painful lumbosacral radiculopathy. “We are encouraged to see that the product will advance to Phase 3 trials in painful lumbosacral radiculopathy, pending discussions with regulators,” said Eric Lang, Channel’s Chief Medical Officer. “While both NaV1.7 and NaV1.8 are voltage-gated sodium channels mainly expressed in sensory neurons, there are important differences in their roles in pain transmission. Research indicates that an over expression of NaV1.8 leads to moderate pain whereas an overexpression of NaV1.7 leads to debilitating pain morbidities, and we believe that NaV1.7 inhibition may be a more potent therapy for pain treatment.” Characteristics of Selective NaV1.7 Inhibition NaV1.7 is a well-studied drug target with strong genetic validation — studies of inheritable pain disorders demonstrate that the spectrum of NaV1.7 activity validates the importance of this target. Lack of NaV1.7 activity leads to the inability to sense pain, whereas NaV1.7 gain of function leads to severe pain. Modulation of NaV1.7, therefore, should be an effective mechanism for decreasing pain. “Channel Therapeutics has chosen a three-pronged approach for our NaV1.7 molecule to demonstrate the utility of this target. We are utilizing an oral NaV1.7 inhibitor for the potential treatment of neuropathic pain starting with Idiopathic Small Fiber neuropathy and Erythromelalgia, a novel eye drop formulation of a NaV1.7 inhibitor to treat eye pain and a novel slow-release depot formulation NaV1.7 inhibitor for post-surgical nerve blocks,” stated Frank Knuettel II, Chief Executive Officer of Channel. “The important differences between NaV1.7 and NaV1.8 not only informs but also differentiates Channel Therapeutics’ approaches to clinical development of the Company’s selective sodium channel blockers CC8464, CT2000 and CT3000. We are very encouraged by the recent data that we have seen from our ongoing programs, including the results from our in vivo nerve block results published earlier this week. As such, we look forward to the upcoming studies and data readouts in 2025 which will serve as critical milestones for which to further substantiate the merits of Channel’s clinical development plan,” Mr. Knuettel concluded. About Channel Channel Therapeutics Corporation is a clinical-stage biotechnology company focused on developing and commercializing novel, non-opioid, non-addictive therapeutics to alleviate pain. The Company’s initial clinical focus is to selectively target the sodium ion-channel known as NaV1.7 for the treatment of various types of chronic pain, acute and chronic eye pain and post-surgical nerve blocks. For company updates and to learn more about Channel, visit www.channeltherapeutics.com or follow us on social media. Forward-Looking Statements This press release contains forward-looking statements regarding the Company’s current expectations. These forward-looking statements include, without limitation, references to the Company’s expectations regarding (i) the Company’s belief that nerve blocks with its NaV1.7 inhibitors may be viable options for the treatment of acute and postoperative pain, (ii) the Company’s belief the Company’s NaV1.7 inhibitor has the potential to improve on existing postoperative therapeutic options while opening the door for success with the Company’s other programs, (iii) the Company’s belief that the NaV1.7 inhibitor may offer a better option for post-surgical physical therapy as compared to bupivacaine, (iv) the Company’s belief that investors should feel encouraged that the Company has a strong development path towards successfully launching drugs with considerable market opportunities, and (iv) the timing of expected results on the Company’s eye drops for the treatment of various types of eye pain. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ materially from those set forth in such forward-looking statements include, but are not limited to, risks and uncertainties related to there being no guarantee that the trading price of the Company’s Common Stock will be indicative of the Company’s value or that the Company’s Common Stock will become an attractive investment in the future. These and other risks and uncertainties are described more fully in in our filings with the U.S. Securities and Exchange Commission. The information in this press release is provided only as of the date of this press release, and we undertake no obligation to update any forward-looking statements contained in this press release based on new information, future events, or otherwise, except as required by law. Channel Media and Investor Inquiries:Mike MoyerManaging Director, LifeSci Advisors, LLCmmoyer@lifesciadvisors.com

Phase 2

19 Dec 2024

·endpts.com

Vertex’s non-opioid pill disappoints in mid-stage chronic pain study

Vertex Pharmaceuticals announced highly anticipated results from a Phase 2 trial Thursday morning in a chronic pain condition, saying its non-opioid pain pill suzetrigine met the primary endpoint and that it would be moving into a Phase 3 study. But the pill appeared to perform similarly to placebo in the trial — raising major questions about the drug’s efficacy in the study and its future in chronic pain. Vertex said that the study was not designed for comparison between the experimental and placebo arms. Vertex’s shares $VRTX fell 13% Thursday in premarket trading on the news. In the Phase 2 study for painful lumbosacral radiculopathy, 102 people received suzetrigine while another 100 received placebo. The study measured change from baseline in daily leg pain intensity on an 11-point pain scale at Week 12. The group that received Vertex’s non-opioid pain pill saw a -2.02 reduction in pain scores from baseline at week 12, meeting the primary endpoint of the study. However, the placebo group saw a reduction of -1.98 over the same period. The p-value for both groups was <0.0001. Vertex said post-hoc analyses showed that “there was variability in the placebo response across study sites, a recognized issue in pain trials.” The company said that in approximately 40% of sites that had lower placebo responses, there was greater separation between the placebo and treatment groups. The company said that “trial design innovation may better control the placebo response and separate the treatment effect of suzetrigine from placebo in future studies, which Vertex will incorporate as it designs the pivotal program.” On safety, Vertex said that 22.9% of people in the suzetrigine arm experienced adverse events compared to 32.4% with placebo, and that there were no serious adverse events related or possibly related to the experimental drug. Vertex is awaiting an FDA decision early next year on its non-opioid pain pill for acute pain, where it is expected to win approval from regulators after passing two late-stage studies. The decision has been closely watched: According to Vertex, it could mark the first new class of pain drug to make it to market in over two decades. If approved, the drug would compete against cheap and widely available opioids. Vertex is also studying suzetrigine in a late-stage study in diabetic peripheral neuropathy.

Clinical ResultPhase 2Phase 3

19 Dec 2024

·www.pharmaceutical-technology.com

Vertex’s stock hurt after non-opioid pain drug shows benefit similar to placebo

The company’s stock has dropped by 15% after the Phase II trial data was announced. Image credit: Shutterstock / pathdoc Vertex Pharmaceuticals ’s non-opioid-based pain therapy has shown benefit in a Phase II trial in patients with painful lumbosacral radiculopathy (LSR) but is not too dissimilar to placebo. The trial (NCT06176196), evaluating suzetrigine, an investigational, oral, highly selective NaV1.8 pain signal inhibitor met its primary endpoint with a statistically significant and clinically meaningful reduction in pain on the numeric pain rating scale (NPRS). The 11-point scale ranges from 0 (no pain) to 10 (worst pain imaginable). The suzetrigine arm showed a statistically significant and clinically meaningful within-group reduction from baseline in pain with a mean change in NPRS of -2.02. The placebo arm was only 0.04 points worse, with a mean change in NPRS of -1.98. Vertex clarified that the study was not designed nor powered for statistical comparison between suzetrigine and placebo. Investors were not convinced by Vertex’s bullish outlook on its data, with the company’s stock falling by 15.53% compared to market close yesterday (18 December). Vertex also conducted post-hoc analyses to further evaluate the efficacy results which showed variability in the placebo response across study sites, a recognised issue in pain trials. The analysis suggest that trial design innovation may better control the placebo response and separate the treatment effect of suzetrigine from placebo in future studies, which Vertex will incorporate as it designs the pivotal programme. Secondary and other endpoints were consistent with the study’s primary endpoint. Suzetrigine was also generally well tolerated in the study, with a 22.9% incidence of adverse events (AEs). There were no serious AEs or AEs leading to treatment discontinuation in patients treated with suzetrigine. Dr. Carmen Bozic, executive vice president of global medicines development and medical affairs, said: “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. We remain committed to studying LSR and innovating our Phase III study design to control for the placebo effect as we advance suzetrigine into pivotal development for this condition.” Suzetrigine is a voltage-gated sodium channel inhibitor, specifically targeting NaV1.8. This channel is expressed in peripheral pain-sensing neurons, known as nociceptors, and plays a role in propagating pain signals. Vertex completed a new drug application (NDA) submission to the US Food and Drug Administration (FDA) for the drug, with a Prescription Drug User Fee Act (PDUFA) target action date of 30 January 2025. Suzetrigine demonstrated positive results in two randomised Phase III trials in patients with moderate-to-severe acute pain including in patients who underwent abdominoplasty (NCT05558410), commonly known as tummy tucks, and bunionectomies (NCT05553366).

Clinical ResultPhase 2Phase 3NDA

100 Deals associated with Suzetrigine

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Acute Pain	NDA/BLA	US	Vertex Pharmaceuticals, Inc.	18 Apr 2024
Diabetic peripheral neuropathic pain	Phase 3	US	Vertex Pharmaceuticals, Inc.	01 Oct 2024
Lumbosacral Radiculopathy	Phase 2	US	Vertex Pharmaceuticals, Inc.	13 Dec 2023
Pain	Phase 1	AU	Vertex Pharmaceuticals, Inc.	15 Dec 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT06176196 (Company_Website) Manual	Phase 2	Lumbosacral Radiculopathy	217	Suzetrigine	wqsqedvoad(shaukcaqjl) = tiwlzfncem fuufmhrfka (gfcojohgdt, -2.40 to -1.64) Met View more	Positive	19 Dec 2024
				Placebo	wqsqedvoad(shaukcaqjl) = fiuziwcabk fuufmhrfka (gfcojohgdt, -2.36 to -1.60) Met View more
Biospace Manual	Phase 3	Pain	-	Suzetrigine	wangyfrejv(redcjghiza) = rejtebkygc zywasvthtd (jcjicvfait ) View more	Positive	21 Oct 2024
				Hydrocodone bitartrate/acetaminophen (HB/APAP)	wangyfrejv(redcjghiza) = ibvcrstdtf zywasvthtd (jcjicvfait ) View more
NCT05661734 (PipelineReview) Manual	Phase 3	Acute Pain	256	VX-548	kiqgcqssdx(rfgpwwtndk) = mostly mild or moderate kuokwbtdcx (ureyhszqwe ) View more	Positive	30 Jan 2024
NCT05558410 (PipelineReview) Manual	Phase 3	Acute Pain	1,118	VX-548	dihyixzsti(pvnjurmdac) = zozkpaszxc vdngjhsbca (ynyqnqmrbv, 4.3) View more	Positive	30 Jan 2024
				Hydrocodone bitartrate/acetaminophen	dihyixzsti(gcvdnexlyz) = quzukpxcod bmzjauirji (lpyrmidzig, 4.3)
NCT05553366 (PipelineReview) Manual	Phase 3	Acute Pain	1,073	VX-548	ekqkzaffsy(mbbuaodfgj) = goseotluxf hdcxlvbluk (rwamuvyqsk, 4.5) View more	Positive	30 Jan 2024
				Hydrocodone bitartrate/acetaminophen	ekqkzaffsy(gnzttfwxjm) = bxfuygrtge oqnmhvpyvz (zgoenpkojd )
NCT05660538 (Corporate Publications) Manual	Phase 2	Diabetic peripheral neuropathy	192	VX-548 23 mg qd	mwpgkprouo(qswdzfmjqa) = vxkfpdaddt omfnobemkh (mitebtirvk, 0.39) View more	Positive	13 Dec 2023
				VX-548 46 mg qd	mwpgkprouo(qswdzfmjqa) = byyfvckftq omfnobemkh (mitebtirvk, 0.28) View more
NCT05034952 (VX21-548-102, Literature) Manual	Phase 2	Acute Pain	303	VX-548 (Abdominoplasty; the high-dose group)	enfzykyxge(udumdkllll) = xjtdjymaux cfbcnpzqrm (fcdjqfwide, 10.3) View more	Positive	03 Aug 2023
				VX-548 (Abdominoplasty; the middle-dose group)	enfzykyxge(udumdkllll) = pfphdcjght cfbcnpzqrm (fcdjqfwide, 10.4) View more
NCT04977336 (VX21-548-101, PipelineReview) Manual	Phase 3	Acute Pain	274	VX-548 (bunionectomy trial; high-dose)	yuayrysmja(bfognnsqkt) = nwwppqdncq cmwzuziyrr (gvyjvaipky, 11.5) View more	Positive	03 Aug 2023
				VX-548 (bunionectomy trial; middle-dose)	yuayrysmja(bfognnsqkt) = wqsowadnax cmwzuziyrr (gvyjvaipky, 11.3) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Suzetrigine

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation