Vertex Announces Results From Phase 2 Study of Suzetrigine for the Treatment of Painful Lumbosacral Radiculopathy
Vertex Pharmaceuticals announced results from its Phase 2 study of suzetrigine for painful lumbosacral radiculopathy (LSR). The study met its primary endpoint with a -2.02 point reduction in pain on the Numeric Pain Rating Scale (NPRS), though the placebo arm showed a similar reduction of -1.98 points.
The drug was generally well tolerated with lower adverse events (22.9%) compared to placebo (32.4%). No serious adverse events related to suzetrigine were reported. Post-hoc analyses revealed variability in placebo response across study sites, with better treatment separation in sites with lower placebo responses.
Vertex plans to advance to Phase 3 development for LSR pending regulatory discussions, incorporating learnings to better control placebo response in future studies.
Vertex Pharmaceuticals ha annunciato i risultati del suo studio di Fase 2 su suzetrigina per la radicolopatia lombo-sacrale dolorosa (LSR). Lo studio ha raggiunto il suo obiettivo primario con una riduzione di -2,02 punti nel punteggio di dolore secondo la Scala Numerica di Valutazione del Dolore (NPRS), sebbene il gruppo placebo abbia mostrato una riduzione simile di -1,98 punti.
Il farmaco è stato generalmente ben tollerato con un'incidenza di eventi avversi più bassa (22,9%) rispetto al placebo (32,4%). Non sono stati riportati eventi avversi gravi correlati a suzetrigina. Le analisi post-hoc hanno rivelato una variabilità nella risposta al placebo tra i siti dello studio, con una migliore separazione del trattamento nei siti con risposte al placebo più basse.
Vertex prevede di avanzare verso lo sviluppo di Fase 3 per LSR in attesa di discussioni regolatorie, incorporando le informazioni acquisite per meglio controllare la risposta al placebo negli studi futuri.
Vertex Pharmaceuticals anunció los resultados de su estudio de Fase 2 de suzetrigina para la radiculopatía lumbosacra dolorosa (LSR). El estudio cumplió con su objetivo primario con una reducción de -2.02 puntos en la Escala de Calificación Numérica del Dolor (NPRS), aunque el grupo placebo mostró una reducción similar de -1.98 puntos.
El fármaco fue generalmente bien tolerado con menores eventos adversos (22.9%) en comparación con el placebo (32.4%). No se informaron eventos adversos graves relacionados con suzetrigina. Los análisis post-hoc revelaron variabilidad en la respuesta al placebo entre los sitios del estudio, con una mejor separación del tratamiento en los sitios con respuestas al placebo más bajas.
Vertex planea avanzar a la Fase 3 para LSR pendientes de discusiones regulatorias, incorporando los aprendizajes para controlar mejor la respuesta al placebo en futuros estudios.
Vertex Pharmaceuticals는 고통스러운 요추-천추 신경근병증(LSR)을 위한 수제트리진의 2상 연구 결과를 발표했습니다. 이 연구는 숫자 통증 척도(NPRS)에서 통증이 -2.02점 감소하는 1차 평가변수를 충족했지만, 위약군에서도 -1.98점 감소가 비슷하게 나타났습니다.
이 약물은 일반적으로 잘 견딜 수 있는 것으로 나타났으며, 부작용 발생률은 위약에 비해 낮았습니다(22.9% vs 32.4%). 수제트리진과 관련된 심각한 부작용은 보고되지 않았습니다. 사후 분석에서는 연구 장소별로 위약 반응의 변동성이 드러났으며, 위약 반응이 낮은 장소에서의 치료 구분이 더 잘 이루어졌습니다.
Vertex는 규제 논의가 기다려지는 가운데 LSR을 위해 3상 개발로 나아갈 계획이며, 향후 연구에서 위약 반응을 더 잘 통제할 수 있도록 배운 점을 반영할 것입니다.
Vertex Pharmaceuticals a annoncé les résultats de son étude de Phase 2 sur la suzetrigine pour la radiculopathie lombo-sacrée douloureuse (LSR). L'étude a atteint son objectif principal avec une réduction de -2,02 points sur l'Échelle Numérique de Notation de la Douleur (NPRS), bien que le groupe placebo ait montré une réduction similaire de -1,98 points.
Le médicament a été généralement bien toléré avec un taux d'événements indésirables inférieur (22,9%) par rapport au placebo (32,4%). Aucun événement indésirable grave lié à la suzetrigine n'a été signalé. Les analyses post-hoc ont révélé une variabilité dans la réponse au placebo selon les sites d'étude, avec une meilleure séparation du traitement dans les sites affichant de plus faibles réponses au placebo.
Vertex prévoit d'avancer vers le développement de Phase 3 pour la LSR, en attendant des discussions réglementaires, en intégrant les enseignements tirés pour mieux contrôler la réponse au placebo dans les futures études.
Vertex Pharmaceuticals hat die Ergebnisse seiner Phase-2-Studie zu Suzetrigine bei schmerzhafter lumbosakraler Radikulopathie (LSR) bekannt gegeben. Die Studie hat den primären Endpunkt erreicht, mit einer Reduktion von -2,02 Punkten auf der Numerischen Schmerzbewertungsskala (NPRS), während die Placebo-Gruppe eine ähnliche Reduktion von -1,98 Punkten zeigte.
Das Medikament wurde generell gut vertragen und zeigte geringere Nebenwirkungen (22,9%) im Vergleich zum Placebo (32,4%). Es wurden keine schwerwiegenden Nebenwirkungen in Verbindung mit Suzetrigine berichtet. Post-hoc-Analysen ergaben eine Variabilität in der Placebo-Reaktion über die Studienstandorte hinweg, wobei an Standorten mit niedrigeren Placebo-Reaktionen eine bessere Behandlungstrennung festgestellt wurde.
Vertex plant, in die Phase-3-Entwicklung für LSR überzugehen, vorbehaltlich regulatorischer Gespräche, und wird die gewonnenen Erkenntnisse nutzen, um zukünftige Studien besser auf die Kontrolle der Placebo-Reaktion auszurichten.
- Met primary endpoint with statistically significant pain reduction (-2.02 points)
- Lower adverse events rate (22.9%) compared to placebo (32.4%)
- No serious adverse events related to treatment
- No treatment discontinuations due to adverse events
- No meaningful separation from placebo effect (-1.98 points)
- High placebo response affecting trial results
- Additional trial design modifications needed for Phase 3 to control placebo effect
Insights
The Phase 2 study results for suzetrigine in painful lumbosacral radiculopathy (LSR) present a complex scenario. While the drug achieved its primary endpoint with a
The safety profile is notably strong, with lower adverse event rates in the suzetrigine arm (
For investors, the path forward depends heavily on Vertex's ability to execute an innovative Phase 3 trial design that can better control the placebo effect - a notorious challenge in pain studies that has derailed many promising candidates. The parallel development in diabetic peripheral neuropathy and acute pain provides some risk mitigation.
The market implications of these results are nuanced. While meeting the technical primary endpoint, the lack of differentiation from placebo adds uncertainty to suzetrigine's commercial potential in LSR. This development slightly increases the risk profile of Vertex's pain portfolio, though the impact is moderated by the drug's progress in other indications, particularly the pending FDA review for acute pain with a PDUFA date of January 2025.
For a company with a
The stock impact should be given Vertex's diversified pipeline and strong core business. However, watch for potential volatility around the upcoming January 2025 PDUFA date for acute pain, which becomes relatively more important for the pain franchise's overall value proposition.
– Treatment with the highly selective NaV1.8 pain signal inhibitor suzetrigine met the primary endpoint with a statistically significant and clinically meaningful 2.02 point within-group reduction from baseline in the Numeric Pain Rating Scale (NPRS) –
– Placebo arm showed similar within-group reduction in NPRS –
– Suzetrigine was generally well tolerated –
– Advancement to Phase 3 in painful lumbosacral radiculopathy planned, pending discussions with regulators –
– Vertex to host investor call on December 19 at 8:00 a.m. ET –
Efficacy Results
The study’s primary endpoint was a within-group change from baseline in the weekly average of daily leg pain intensity on the NPRS at Week 12. This 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 at Week 12 of -2.02.
The study also included a placebo reference arm which showed a similar within-group reduction from baseline in pain with a mean change in NPRS at Week 12 of -1.98. The study was not designed nor powered for statistical comparison between suzetrigine and placebo.
|
Suzetrigine
|
Placebo
|
Baseline NPRS |
|
|
Mean NPRS (SD) |
6.33 (1.22) |
6.05 (1.07) |
Change in NPRS from baseline at Week 12 |
|
|
LS mean |
-2.02 |
-1.98 |
|
(-2.40, -1.64) |
(-2.36, -1.60) |
P value |
<0.0001 |
<0.0001 |
Secondary and other endpoints were consistent with the study’s primary endpoint.
Vertex also conducted post-hoc analyses to further evaluate the efficacy results. These showed that there was variability in the placebo response across study sites, a recognized issue in pain trials. In the ~
Safety Results
Suzetrigine was generally well tolerated in the study. The incidence of adverse events (AEs) was
|
Suzetrigine
|
Placebo
|
Subjects with any AEs |
25 (22.9) |
35 (32.4) |
Subjects with AEs by strongest relationship |
||
Not related |
16 (14.7) |
20 (18.5) |
Unlikely related |
1 (0.9) |
6 (5.6) |
Possibly related |
6 (5.5) |
8 (7.4) |
Related |
2 (1.8) |
1 (0.9) |
Subjects with AEs by maximum severity |
||
Grade 1/Mild |
15 (13.8) |
17 (15.7) |
Grade 2/Moderate |
10 (9.2) |
17 (15.7) |
Grade 3/Severe |
0 |
1 (0.9) |
Grade 4/Life-threatening |
0 |
0 |
Grade 5/Death |
0 |
0 |
Subjects with serious AEs |
1 (0.9) |
2 (1.9) |
Subjects with AEs leading to treatment discontinuation |
0 |
1 (0.9) |
Subjects with AEs leading to death |
0 |
0 |
“Suzetrigine has again demonstrated its potential to fill an important unmet need in the treatment of pain. Today's LSR results are consistent with previous studies of this pain signal inhibitor in terms of showing a meaningful treatment effect across pain conditions and a favorable safety profile,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “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 3 study design to control for the placebo effect as we advance suzetrigine into pivotal development for this condition.”
“The suzetrigine Phase 2 results clearly show reduced pain intensity from baseline in the active drug arm, and the potential for suzetrigine to fill an unmet need in relieving LSR pain, a heterogeneous condition that is notoriously difficult to treat,” said Christine Sang, M.D., M.P.H., FASA, Director, Translational Pain Research, Brigham and Women's Hospital, Associate Professor of Anesthesia, Harvard Medical School, co-chair of Vertex’s Peripheral Neuropathic Pain steering committee, and lead principal investigator on the study. “Managing the placebo response in pain trials is a complex challenge. We look forward to innovating in clinical trial design, including for the pivotal study, with the aim of bringing a potentially safe and effective treatment to patients suffering from LSR."
Next Steps for the Pain Portfolio
Neuropathic Pain
Vertex plans to advance suzetrigine into pivotal development for painful LSR following discussions with regulators on the study design and regulatory package. The company will apply learnings from analysis of the full Phase 2 data set and post-hoc analyses to inform the Phase 3 study design.
Earlier this year, Vertex initiated its suzetrigine pivotal program in painful diabetic peripheral neuropathy (DPN), another type of peripheral neuropathic pain (PNP). That study is ongoing.
Acute Pain
Additionally, as previously announced, suzetrigine is under FDA review for the treatment of moderate-to-severe acute pain. The agency granted priority review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2025.
In line with its portfolio strategy, Vertex continues to advance preclinical and clinical development of additional NaV1.8 and NaV1.7 inhibitors, for use alone or in combination, in acute and neuropathic pain.
Conference Call and Webcast
The company will host a conference call and webcast at 8:00 a.m. ET on Thursday, December 19, 2024. To access the call, please dial (833) 630-2124 (
The conference call will be webcast live and a link to the webcast can be accessed through Vertex's website at www.vrtx.com in the "Investors" section. To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast. An archived webcast will be available on the company's website.
About the Phase 2 Suzetrigine Lumbosacral Radiculopathy (LSR) Study
This phase 2, 12-week, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of suzetrigine in treating patients with painful LSR. A total of 218 patients were enrolled in the study and randomized 1:1 with suzetrigine or placebo. The primary endpoint was the within-group change from baseline in the weekly average of daily leg pain intensity on a numeric pain rating scale (NPRS) at Week 12. The study also included a placebo reference arm; however, the study was not designed nor powered for comparison between suzetrigine and placebo.
Secondary endpoints assessed the within-group change from baseline in the weekly average of the daily sleep interference scale at Week 12 and safety and tolerability. By blocking the pain signal from the peripheral sensory neurons, Vertex believes that suzetrigine may alleviate the suffering for millions of patients with painful LSR.
About Painful Lumbosacral Radiculopathy (LSR)
Painful lumbosacral radiculopathy, or LSR, is one of the most common causes of peripheral neuropathic pain. It is pain caused by impairment of nerve roots in the area of the lumbar spine. It often results in radiating pain along the distribution of the impacted nerve in the body, and patients can experience back and leg pain, sensory issues or motor dysfunction. Common causes of LSR include nerve compression from a herniated disk, or arthritic or degenerative changes in the area of the lower spine. LSR is a neuropathic pain condition because the impacted nerve roots are part of the peripheral nervous system and not part of the spinal cord. Millions of patients suffer from pain due to LSR every year.
About Suzetrigine
Suzetrigine is an investigational oral, highly selective pain signal inhibitor that is selective for NaV1.8 relative to other NaV channels. NaV1.8 is a voltage-gated sodium channel that is selectively expressed in peripheral pain-sensing neurons (nociceptors), where its role is to transmit pain signals (action potentials). Vertex’s approach is to selectively inhibit NaV1.8 using small molecules with the objective of creating a new class of pain signal inhibitors that have the potential to provide effective relief of pain without the limitations of currently available therapies, including the addictive potential of opioids. Suzetrigine has demonstrated a favorable benefit/risk profile in multiple Phase 2 and Phase 3 studies in patients with moderate-to-severe acute pain and has been granted FDA Fast Track and Breakthrough Therapy designations in moderate-to-severe acute pain in the
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, primary membranous nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes and myotonic dystrophy type 1.
Vertex was founded in 1989 and has its global headquarters in
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements by Carmen Bozic, M.D., and Christine Sang, M.D., M.P.H., FASA, in this press release, and statements regarding Vertex’s beliefs about the potential benefits of suzetrigine for patients with LSR, plans to advance suzetrigine to Phase 3 pending discussions with regulators, plans and expectations for the design of the pivotal program, plans to apply learnings from the Phase 2 data and post-hoc analyses to inform the Phase 3 study design, including beliefs that trial design innovation may better control the placebo response and separate the treatment effect of suzetrigine from placebo in future studies, and our plans to continue to advance preclinical and clinical development of additional NaV1.8 and NaV1.7 inhibitors in acute and neuropathic pain. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the clinical program evaluating suzetrigine as a treatment for LSR may not support registration or further development of its compounds due to safety, efficacy or other reasons, that discussions with regulators may have different outcomes than the company anticipates, and other risks listed under the heading “Risk Factors” in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at www.sec.gov and available through the company's website at www.vrtx.com. You should not place undue reliance on these statements, or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.
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