The efficacy of JOURNAVXTM was demonstrated in 2 randomized, double-blind, placebo- and hydrocodone bitartrate/acetaminophen (HB/APAP)–controlled trials of moderate-to-severe acute pain1
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STUDY DESIGN
How JOURNAVX was evaluated1
STUDY ENDPOINTS
What was measured
The primary endpoint in both trials was JOURNAVX superiority vs placebo on the time-weighted sum of the pain intensity difference (SPID) as recorded on the Numeric Pain Rating Scale (NPRS) from 0 to 48 hours (SPID48).1-3
Key secondary endpoints included JOURNAVX superiority vs HB/APAP on SPID48 and time to ≥2 point reduction in NPRS from baseline compared to placebo.1-3
Other endpoints included2,3:
Time to ≥1 point reduction in NPRS from baseline compared to placebo
Incidence of vomiting or nausea
Safety and tolerability as assessed by number of participants with adverse events and serious adverse events
STUDY METRICS
What is SPID48?
The time-weighted sum of the pain intensity difference (SPID) as recorded on the Numeric Pain Rating Scale from 0 to 48 hours
Referenced by FDA Guidance for Industry as an important and commonly used endpoint in clinical trials that allows for assessment of the effectiveness of acute pain management interventions4
SPID48 is derived from NPRS scores and reflects a cumulative measure of pain relief captured over a 48-hour period.1,4,5 In each trial, pain intensity was measured using a patient-reported 11-point NPRS, ranging from 0 to 10, where 0 corresponds to no pain and 10 corresponds to the worst pain imaginable1
Time-weighted SPID as recorded on the NPRS from 0 to 48 hours (SPID48)6
(For illustrative purposes only)
Higher SPID values represent greater reductions in pain.7
STUDY POPULATION
KEY DEMOGRAPHICS | Trial 1: Abdominoplastya-c | Trial 2: Bunionectomya-c |
|---|---|---|
Number of adult patients with moderate-to-severe acute pain | 1118 (JOURNAVX n=447, placebo n=223, | 1073 (JOURNAVX n=426, placebo n=216, |
Mean baseline pain score | 7.4 (range: 4 to 10) | 6.8 (range: 4 to 10) |
Female (%) | 98 | 85 |
Mean age (years) | 42 (range: 18 to 69) | 48 (range: 18 to 75) |
Race (%)d | ||
White | 70 | 71 |
Black/African American | 27 | 24 |
Asian | 1 | 2 |
Native Hawaiian/Other Pacific Islander | 0.8 | 0.2 |
American Indian/Alaska Native | 0.5 | 1 |
Other or Multiracial | 0.9 | 1 |
a For both studies, 400 mg of ibuprofen every 6 hours, as needed for pain relief, was permitted as a rescue medication across all treatment groups.1
b In each trial, pain intensity was measured using a patient-reported 11-point NPRS, ranging from 0 to 10, where 0 corresponds to no pain and 10 corresponds to the worst pain imaginable. Patients were eligible for study participation if they had moderate-to-severe acute pain on the Verbal Categorical Rating Scale (VRS) and a pain score of ≥4 on the NPRS, within 4 hours of the abdominoplasty completion or during the 9-hour period after discontinuation of regional anesthesia following bunionectomy.1
c All baseline characteristics, including NPRS, VRS, and body mass index (BMI) were generally balanced across treatment groups.1
d In Trial 2, race information was missing for 0.3% of participants.1
TRIAL 1: ABDOMINOPLASTY
JOURNAVX met the primary endpoint by demonstrating statistically significant superior reduction in pain vs placebo.
JOURNAVX did not meet the first key secondary endpoint that hypothesized superior reduction in pain vs HB/APAP.1,8
e As measured by the time-weighted sum of the pain intensity difference (SPID) as recorded on the Numeric Pain Rating Scale (NPRS) from 0 to 48 hours (SPID48).
f A larger value of LS mean indicates better efficacy measured by SPID48.
CI, confidence interval; LS, least squares; SE, standard error.
SPID48 results1,9
EFFICACY | JOURNAVX | PLACEBO | HB/APAP |
|---|---|---|---|
LS meanf (SE) | 118.4 (4.3) | 70.1 (6.1) | 111.8 (4.3) |
LS mean difference from placebo (95% CI) | 48.4 (33.6, 63.1)
P<.0001 | - | - |
e As measured by the time-weighted sum of the pain intensity difference (SPID) as recorded on the Numeric Pain Rating Scale (NPRS) from 0 to 48 hours (SPID48).
f A larger value of LS mean indicates better efficacy measured by SPID48.
CI, confidence interval; LS, least squares; SE, standard error.
Mean pain intensity over time1,g
The NPRS vs time analysis was not a prespecified study objective. It is not intended to convey a measure of efficacy.
g 400 mg of ibuprofen every 6 hours, as needed for pain relief, was permitted as a rescue medication across all treatment groups. Pre-rescue pain scores were carried forward for 6 hours following the use of rescue medication.1
EFFICACY | JOURNAVX | PLACEBO | HB/APAP |
|---|---|---|---|
Baseline NPRS, mean | 7.3 | 7.5 | 7.4 |
Change from baseline in NPRS, mean | -3.4 | -2.3 | -3.2 |
% reduction from baseline in mean NPRS | 47% | 31% | 43% |
Reduction in pain scores at 48 hours of treatment10
The data in the table are for illustrative purposes only and not intended for comparative analysis.
The data in the table are for illustrative purposes only and not intended for comparative analysis.
The data in the table are for illustrative purposes only and not intended for comparative analysis.
TRIAL 2: BUNIONECTOMY
acute pain vs placebo confirmed in second trial1,h
JOURNAVX also met the primary endpoint in Trial 2 by demonstrating statistically significant superior reduction in pain vs placebo.
JOURNAVX did not meet the key secondary endpoint that hypothesized superior reduction in pain vs HB/APAP.1,8
h As measured by the time-weighted sum of the pain intensity difference (SPID) as recorded on the Numeric Pain Rating Scale (NPRS) from 0 to 48 hours (SPID48).
i A larger value of LS mean indicates better efficacy measured by SPID48.
SPID48 results1,9
EFFICACY | JOURNAVX | PLACEBO | HB/APAP |
|---|---|---|---|
LS meani (SE) | 99.9 (4.5) | 70.6 (6.3) | 120.1 (4.5) |
LS mean difference from placebo (95% CI) | 29.3 (14.0, 44.6)
P=.0002 | - | - |
h As measured by the time-weighted sum of the pain intensity difference (SPID) as recorded on the Numeric Pain Rating Scale (NPRS) from 0 to 48 hours (SPID48).
i A larger value of LS mean indicates better efficacy measured by SPID48.
Mean pain intensity over time1,j
The NPRS vs time analysis was not a prespecified study objective. It is not intended to convey a measure of efficacy.
j 400 mg of ibuprofen every 6 hours, as needed for pain relief, was permitted as a rescue medication across all treatment groups. Pre-rescue pain scores were carried forward for 6 hours following the use of rescue medication.1
EFFICACY | JOURNAVX | PLACEBO | HB/APAP |
|---|---|---|---|
Baseline NPRS, mean | 6.7 | 6.8 | 6.8 |
Change from baseline in NPRS, mean | -3.4 | -2.6 | -3.6 |
% reduction from baseline in mean NPRS | 51% | 38% | 53% |
Reduction in pain scores at 48 hours of treatment10
The data in the table are for illustrative purposes only and not intended for comparative analysis.
The data in the table are for illustrative purposes only and not intended for comparative analysis.
The data in the table are for illustrative purposes only and not intended for comparative analysis.
TIME TO ONSET
Time to onset of pain relief 1
TRIAL 1
Abdominoplasty
Median time to ≥2 point reduction in NPRS from baseline (clinically meaningful pain relief)1,11
119 minutes for patients taking JOURNAVX
480 minutes for patients taking placebo
Median time to ≥1 point reduction in NPRS (perceptible pain relief)1
34 minutes for patients taking JOURNAVX
TRIAL 2
Bunionectomy
Median time to ≥2 point reduction in NPRS from baseline (clinically meaningful pain relief)1,11
240 minutes for patients taking JOURNAVX
480 minutes for patients taking placebo
Median time to ≥1 point reduction in NPRS (perceptible pain relief)1
60 minutes for patients taking JOURNAVX
The data above are for illustrative purposes only and not intended for comparative analysis.
References: 1. JOURNAVX [prescribing information]. Vertex Pharmaceuticals Incorporated. Boston, MA; January 2025. 2. National Institutes of Health. Evaluation of efficacy and safety of VX-548 for acute pain after an abdominoplasty. Update March 20, 2024. Accessed March 1, 2025. https://clinicaltrials.gov/study/NCT05558410 3. National Institutes of Health. Evaluation of efficacy and safety of VX-548 for acute pain after a bunionectomy. Update March 20, 2024. Accessed March 1, 2025. https://clinicaltrials.gov/study/NCT05553366 4. Development of non-opioid analgesics for acute pain: guidance for industry. US Food and Drug Administration. February 2022. Accessed March 1, 2025. https://www.fda.gov/media/156063/download 5. Tripathi AP, Shanker R. Sample size estimation for a non-inferiority pain management trial. The Open Pain Journal. 2023;16:e187638632301260. doi:10.2174/18763863-v16-e230202-2022-6 6. Singla NK, Meske DS, Desjardins PJ. Exploring the interplay between rescue drugs, data imputation, and study outcomes: conceptual review and qualitative analysis of an acute pain data set [published correction appears in Pain Ther. 2017 Dec;6(2):177-178. doi:10.1007/s40122-017-0078-1]. Pain Ther. 2017;6(2):165-175. doi:10.1007/s40122-017-0074-5 7. Jones J, Correll DJ, Lechner SM, et al. Selective inhibition of NaV1.8 with VX-548 for acute pain. N Engl J Med. 2023;389(5):393-405. doi:10.1056/NEJMoa2209870 8. Bertoch T, D’Aunno D, McCoun J, et al. Randomized, placebo-controlled, phase 3 trials of suzetrigine, a non-opioid, pain signal inhibitor for treatment of acute pain after abdominoplasty or bunionectomy. Presented at: ASA Annual Medicine Meeting; October 18-22, 2024; Philadelphia, PA. 9. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-28512 (v1.0); 2024. 10. Data on file. Vertex Pharmaceuticals Incorporated. Boston, MA. REF-28505 (v1.0); 2024. 11. Farrar JT, Berlin JA, Strom BL. Clinically important changes in acute pain outcome measures: a validation study. J Pain Symptom Manage. 2003;25(5):406-411.
INDICATION
JOURNAVX is indicated for the treatment of moderate-to-severe acute pain in adults.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Concomitant use of JOURNAVX with strong CYP3A inhibitors is contraindicated.
WARNINGS AND PRECAUTIONS
INDICATION
JOURNAVX is indicated for the treatment of moderate-to-severe acute pain in adults.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
Concomitant use of JOURNAVX with strong CYP3A inhibitors is contraindicated.
WARNINGS AND PRECAUTIONS
Increased Risk of Adverse Reactions With Concomitant Use With Strong and Moderate CYP3A Inhibitors: Strong and moderate CYP3A inhibitors increase suzetrigine and its active metabolite exposures, which may cause adverse reactions with JOURNAVX.
Risk of Drug Interactions With Certain CYP3A Substrates: Suzetrigine is an inducer of CYP3A. If JOURNAVX is used concomitantly with sensitive CYP3A substrates or CYP3A substrates where minimal concentration changes may lead to loss of efficacy, refer to the Prescribing Information for the CYP3A substrates for dosing instructions. Dosage adjustment of the concomitant CYP3A substrates may be required when initiating or discontinuing JOURNAVX.
Risk of Drug Interactions With Certain Hormonal Contraceptives: Patients treated with JOURNAVX who are taking concomitant hormonal contraceptives containing progestins other than levonorgestrel and norethindrone should use additional nonhormonal contraceptives (such as condoms) or use alternative contraceptives during JOURNAVX treatment and for 28 days after discontinuation of JOURNAVX.
Risk of Adverse Reactions in Patients With Moderate and Severe Hepatic Impairment: Patients with moderate hepatic impairment have higher systemic exposures of suzetrigine and its active metabolite than those with normal hepatic function, which may increase the risk of JOURNAVX-related adverse reactions.
ADVERSE REACTIONS
Pooled adverse reactions from Trials 1 and 2 that occurred in ≥1% of patients treated with JOURNAVX and at a greater rate than patients treated with placebo were pruritus, muscle spasms, increased blood creatine phosphokinase, and rash. The safety profile of JOURNAVX in Trial 3 was consistent with that observed in Trials 1 and 2.
DRUG INTERACTIONS
Effect of Other Drugs on JOURNAVX
CYP3A Inhibitors: A reduced dose is recommended when coadministered with moderate CYP3A inhibitors. Avoid food or drink containing grapefruit.
Strong and Moderate CYP3A Inducers: Avoid concomitant use of JOURNAVX with strong and moderate CYP3A inducers. Concomitant use of strong or moderate CYP3A inducers results in reduced exposures of suzetrigine and its active metabolite, which may result in reduced JOURNAVX efficacy.
Effect of JOURNAVX on Other Drugs
CYP3A Substrates: Dose adjustment of the concomitant CYP3A substrates may be required when initiating or discontinuing JOURNAVX. Discontinuation of JOURNAVX may increase the exposure of sensitive CYP3A substrates.
USE IN SPECIFIC POPULATIONS
Pregnancy
There are no available data on the use of JOURNAVX during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
Lactation
There are no data on the presence of suzetrigine or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for JOURNAVX and any potential adverse effects on the breastfed child from JOURNAVX or from the underlying maternal condition.
Infertility
JOURNAVX may reversibly impact the likelihood of females of reproductive potential to become pregnant while on treatment. Patients using contraceptives should continue to use contraceptives.
Geriatric Use
Based on population pharmacokinetic analyses in patients with ages ranging from 18 to 75 years, age does not have a clinically relevant impact on suzetrigine exposure.
Hepatic Impairment
The recommended JOURNAVX dosage is lower in patients with moderate hepatic impairment (Child‑Pugh Class B) than those with normal hepatic function. Avoid use of JOURNAVX in patients with severe hepatic impairment (Child‑Pugh Class C).
Renal Impairment
Avoid use of JOURNAVX in patients with renal impairment of eGFR <15 mL/min.
Please see full Prescribing Information for JOURNAVX.