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RECOVER Clinical Study Shows Meaningful Benefits of LivaNova’s VNS Therapy System in Select Secondary Endpoints for Unipolar Patients with Treatment-Resistant Depression

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LivaNova (Nasdaq: LIVN) announced publication of two pivotal articles in Brain Stimulation journal regarding the RECOVER clinical study of their VNS Therapy System for treatment-resistant unipolar depression. The study involved 493 adults who had failed over 13 antidepressant treatments on average. While not meeting its primary endpoint, the study showed statistically significant benefits in select secondary endpoints. Active VNS Therapy demonstrated meaningful improvements in quality of life and daily function compared to sham treatment. The study revealed significant benefits in Clinical Global Impression-Improvement (CGI-I) (P=0.004) and Quick Inventory of Depressive Symptomology-Self Report (QIDS-SR) (P=0.049). Three additional manuscripts are planned to report further outcomes.

LivaNova (Nasdaq: LIVN) ha annunciato la pubblicazione di due articoli fondamentali nella rivista Brain Stimulation riguardanti lo studio clinico RECOVER del loro sistema di terapia VNS per la depressione unipolare resistente ai trattamenti. Lo studio ha coinvolto 493 adulti che avevano fallito in media più di 13 trattamenti antidepressivi. Anche se non ha raggiunto il suo obiettivo principale, lo studio ha mostrato benefici statisticamente significativi in alcuni obiettivi secondari. La terapia VNS attiva ha dimostrato significativi miglioramenti nella qualità della vita e nelle funzioni quotidiane rispetto al trattamento fittizio. Lo studio ha rivelato benefici significativi nella Clinical Global Impression-Improvement (CGI-I) (P=0.004) e nel Quick Inventory of Depressive Symptomology-Self Report (QIDS-SR) (P=0.049). Sono previsti tre ulteriori manoscritti per riportare ulteriori risultati.

LivaNova (Nasdaq: LIVN) anunció la publicación de dos artículos fundamentales en la revista Brain Stimulation sobre el estudio clínico RECOVER de su sistema de terapia VNS para la depresión unipolar resistente al tratamiento. El estudio involucró a 493 adultos que habían fallado en más de 13 tratamientos antidepresivos en promedio. Aunque no se alcanzó el objetivo principal, el estudio mostró beneficios estadísticamente significativos en algunos objetivos secundarios. La terapia VNS activa demostró mejoras significativas en la calidad de vida y la función diaria en comparación con el tratamiento simulado. El estudio reveló beneficios significativos en la Clinical Global Impression-Improvement (CGI-I) (P=0.004) y en el Quick Inventory of Depressive Symptomology-Self Report (QIDS-SR) (P=0.049). Se planean tres manuscritos adicionales para informar sobre más resultados.

LivaNova (Nasdaq: LIVN)는 RECOVER 임상 연구에 대한 두 개의 주요 기사가 Brain Stimulation 저널에 발표되었음을 알렸습니다. 이 연구는 치료에 저항적인 단극성 우울증 치료를 위한 VNS 치료 시스템에 대한 연구로, 493명의 성인이 참여했으며 평균적으로 13회 이상의 항우울제 치료에 실패했습니다. 주요 목표를 달성하지는 못했지만, 연구는 일부 2차 목표에서 통계적으로 유의미한 혜택을 보였습니다. 활성 VNS 치료는 위약 치료와 비교하여 삶의 질과 일상 기능에서 의미 있는 개선을 보여주었습니다. 연구는 Clinical Global Impression-Improvement (CGI-I) (P=0.004) 및 Quick Inventory of Depressive Symptomology-Self Report (QIDS-SR) (P=0.049)에서 유의미한 혜택을 나타냈습니다. 추가 결과를 보고하기 위한 세 개의 추가 원고가 계획되어 있습니다.

LivaNova (Nasdaq: LIVN) a annoncé la publication de deux articles majeurs dans la revue Brain Stimulation concernant l'étude clinique RECOVER de leur système de thérapie VNS pour la dépression unipolaire résistante au traitement. L'étude a impliqué 493 adultes ayant échoué à plus de 13 traitements antidépresseurs en moyenne. Bien qu'elle n'ait pas atteint son objectif principal, l'étude a révélé des bénéfices statistiquement significatifs dans certains objectifs secondaires. La thérapie VNS active a démontré des améliorations significatives dans la qualité de vie et le fonctionnement quotidien par rapport au traitement simulé. L'étude a révélé des bénéfices significatifs dans la Clinical Global Impression-Improvement (CGI-I) (P=0.004) et le Quick Inventory of Depressive Symptomology-Self Report (QIDS-SR) (P=0.049). Trois manuscrits supplémentaires sont prévus pour rapporter d'autres résultats.

LivaNova (Nasdaq: LIVN) hat die Veröffentlichung von zwei entscheidenden Artikeln in der Zeitschrift Brain Stimulation über die RECOVER-Studie zu ihrem VNS-Therapie-System für behandlungsresistente unipolare Depressionen bekannt gegeben. In der Studie wurden 493 Erwachsene einbezogen, die im Durchschnitt mehr als 13 Antidepressivum-Behandlungen nicht erfolgreich absolvierten. Obwohl das primäre Ziel nicht erreicht wurde, zeigte die Studie statistisch signifikante Vorteile bei bestimmten sekundären Zielen. Die aktive VNS-Therapie zeigte im Vergleich zur Scheinbehandlung bedeutende Verbesserungen in der Lebensqualität und der alltäglichen Funktion. Die Studie offenbarte signifikante Vorteile bei der Clinical Global Impression-Improvement (CGI-I) (P=0.004) und dem Quick Inventory of Depressive Symptomology-Self Report (QIDS-SR) (P=0.049). Drei weitere Manuskripte sind geplant, um weitere Ergebnisse zu berichten.

Positive
  • Demonstrated statistically significant improvements in multiple secondary endpoints
  • Showed meaningful therapeutic effects on depressive symptoms
  • Achieved positive effects on quality of life and daily function
  • Proved safety with no new safety issues identified
  • Strong results in partial response rates across multiple rating scales
Negative
  • Failed to meet primary endpoint due to strong response in sham group
  • Did not show significant differences in suicidal ideation metrics (P=0.239)
  • No significant differences observed in WHODAS 2.0 and EQ-5D visual analog scale

Insights

The RECOVER clinical study results for LivaNova's VNS Therapy System present mixed but promising outcomes. While missing its primary endpoint, the study demonstrated statistically significant improvements in several secondary endpoints. The active VNS group showed superior results in clinical measurements including CGI-I (P=0.004) and QIDS-SR (P=0.049), with notable improvements in quality of life metrics.

The study's scope is substantial, involving 493 severely treatment-resistant patients who had failed an average of 13 previous treatments. This represents a significant market opportunity, as these patients have therapeutic options. The safety profile remains favorable, with no new safety concerns identified, strengthening the therapy's potential for regulatory approval and market adoption.

These results could significantly impact LivaNova's market position in the treatment-resistant depression (TRD) space. While the missed primary endpoint might concern investors, the positive secondary endpoints and quality of life improvements provide strong support for CMS coverage approval. The TRD market represents a substantial opportunity, with effective treatment options available.

The upcoming additional manuscripts and CMS coverage request could be important catalysts for LIVN stock. The market cap of $2.7 billion suggests room for growth if CMS coverage is secured, potentially expanding access to millions of Medicare beneficiaries. The comprehensive data package being prepared strengthens the company's position for successful coverage determination.

Results published in two articles in Brain Stimulation

LONDON--(BUSINESS WIRE)-- LivaNova PLC (Nasdaq: LIVN), a market-leading medical technology company, today announced that the journal Brain Stimulation has published two pivotal articles chronicling the unipolar cohort data set for the RECOVER clinical study. The researchers evaluated the safety and efficacy of LivaNova’s VNS Therapy™ System and its effectiveness on quality of life and daily function in this population of patients with treatment-resistant unipolar depression. Overall, the articles concluded that active VNS Therapy, as compared with a no-stimulation control (or sham VNS Therapy), safely and effectively demonstrated clinically meaningful therapeutic effects on depressive symptoms and positive effects on quality of life and daily function. These findings support the use of VNS Therapy to deliver vagus nerve stimulation (VNS) in treatment-resistant depression (TRD) patients.

A total of 493 adults with at least four documented unsuccessful attempts with antidepressant treatments participated in the unipolar cohort of the RECOVER study. At baseline, unipolar patients in the study failed more than 13 antidepressant treatments (on average) – this included, for the majority, one or more interventional therapies (e.g., transcranial magnetic stimulation, electroconvulsive therapy, or esketamine). While the RECOVER study did not meet the primary endpoint due to a strong and unforeseen response in the sham group, the active treatment arm demonstrated statistically significant and clinically meaningful improvement from the treatment arm’s baseline. Further, the RECOVER study demonstrated statistically significant and clinically meaningful benefits in select secondary endpoints for this cohort. Based upon these findings and the positive effects for those who received VNS Therapy, the Company conducted additional in-depth data analyses and plans to submit three additional critical manuscripts to report on the outcomes.

“Participants in the trial had severe, refractory depression that could not be treated effectively with other FDA-approved treatments, and most have had large portions of their lives profoundly negatively impacted by depression,” said Charles Conway, MD, director of the Washington University Resistant Mood Disorders Center at Washington University School of Medicine in St. Louis. Conway is the study's lead investigator and first author of the mood outcomes article. “For this sample of markedly ill TRD participants, I am encouraged by the findings, which revealed that active VNS performed better than sham VNS treatment in all measures, and that active VNS demonstrated clinically meaningful, safe therapeutic effects. Multiple clinician, patient, and independent observer ratings separated between the active and sham unipolar arms.”

The first article, “Vagus Nerve Stimulation in Treatment-Resistant Depression: A One-Year, Randomized, Sham-Controlled Trial,”1 outlines the safety and effectiveness of adjunctive VNS Therapy in treating patients with unipolar TRD. The primary endpoint measured the difference in the percentage of time in antidepressant response between active VNS Therapy and sham VNS Therapy, with response defined as at least a 50% reduction from baseline using the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. While the predetermined p-value was p<0.023, the observed mean percentage of time in response was p=0.137.

Analyses of secondary endpoints revealed antidepressant benefits significantly favoring active VNS Therapy as opposed to sham VNS Therapy as measured by ratings from on-site clinicians (Clinical Global Impression-Improvement, or CGI-I), patients themselves (Quick Inventory of Depressive Symptomology–Self Report, or QIDS-SR), and offsite masked raters (Quick Inventory of Depressive Symptomology–Clinical, or QIDS-C).

Results included:

  • Participants with active VNS Therapy had significantly more percentage of time in response with CGI-I (P=0.004) and QIDS-SR (P=0.049) compared with sham VNS Therapy.
  • For percentage of time in partial response, active VNS Therapy showed significant benefit with QIDS-C (P=0.006) and CGI-I (P<0.001) compared with sham VNS Therapy. Partial response is defined as improvement of ≥30% from baseline for QIDS-C or a score of ≤3 for CGI-I.
  • No differences between treatment groups were observed in suicidal ideation and intent as measured by the S-STS2 items 6 and 8 (P=0.239).

“The composite of the mood findings, especially in the partial response rates on multiple ratings scales, along with the low rate of adverse events, support that this device demonstrated safe antidepressant efficacy for these patients,” said Conway.

The second article, “Effects of Vagus Nerve Stimulation on Daily Function and Quality of Life in Markedly Treatment-Resistant Major Depression: Findings from a One-Year, Randomized, Sham-Controlled Trial,”3 assesses VNS Therapy’s ability to improve quality of life (QoL) and daily function in patients with unipolar TRD. The results of this analysis demonstrated that adjunctive VNS Therapy provided greater improvements in QoL and daily function in patients with unipolar TRD when compared with sham VNS Therapy.

Results included:

  • The active VNS Therapy group showed greater improvements over the sham control group as measured by the mean change in scores from baseline in the Mini-Q-LES-Q4 (P=0.050) and WPAI5 item 6 (health condition’s effect on regular activities; P=0.050) used as continuous variables.
  • Time spent in a state of clinically meaningful benefit was significantly greater with active VNS Therapy compared to sham VNS Therapy, using the Q-LES-Q6 (P=0.029), Mini-Q-LES-Q (P=0.011) and WPAI item 6 (P=0.039).
  • No differences between treatment groups were observed in the mean change in score from baseline with the WHODAS7 2.0 (P=0.304) and the EQ-5D8 visual analog scale (P=0.125).

“Adjunctive VNS Therapy improves quality of life and psychosocial function in patients with major depression who have not benefited from multiple antidepressant treatments,” said A. John Rush, MD, Professor Emeritus at Duke-National University of Singapore Medical School and lead author on this article. “For these patients who are profoundly impaired, largely unemployed, and markedly treatment-resistant, depressive symptoms alone are an incomplete gauge of the clinical impact of treatments. Symptoms, function, and quality of life taken together present a more complete picture of treatment effectiveness.”

These two articles published in Brain Stimulation are the first in a series that will detail the RECOVER unipolar cohort data. Three subsequent, supportive manuscripts will feature outcomes from in-depth data analyses on select secondary endpoints. The totality of data presented in these five complementary articles will serve as the basis for LivaNova’s formal request to the U.S. Centers for Medicare and Medicaid Services (CMS) for VNS Therapy coverage.

“Patients in the RECOVER study are some of the most critically ill among those with treatment-resistant depression and they need more treatment options when existing therapies fail,” said Vladimir Makatsaria, Chief Executive Officer of LivaNova. “The data from the RECOVER study and predecessor studies has shown that VNS Therapy is a safe and effective treatment option for these patients, providing hope for patients and families in similar situations who have few viable options. We look forward to sharing more of the important outcomes from the unipolar cohort with the intent to offer VNS Therapy as an important adjunctive treatment for these patients.”

RECOVER launched in 2019 as part of a Coverage with Evidence Development framework per the CMS National Coverage Determination process. For the unipolar cohort of RECOVER, enrollment was completed in March 2023, and the 12-month follow-up for those patients was completed in March 2024. No new safety issues were identified in the study.

About RECOVER

LivaNova’s VNS Therapy™ System has been approved for the treatment of depression since earning CE Mark in 2001 and 510(k) from the U.S. Food and Drug Administration in 2005. RECOVER stands for A Prospective, Multi-center, Randomized Controlled Blinded Trial Demonstrating the Safety and Effectiveness of VNS Therapy System as Adjunctive Therapy Versus a No Stimulation Control in Subjects With Treatment-Resistant Depression.

The largest randomized clinical study of its kind, RECOVER is examining up to 1,000 patients ages 18 or older who have unipolar or bipolar depression that is difficult to treat. The double-blind, randomized controlled study is assessing how VNS Therapy can offer patients relief from their depressive symptoms and improve quality of life. It is being carried out at up to 100 leading hospitals and medical centers across the United States.

About VNS Therapy for Depression

The VNS Therapy™ System, Symmetry™, is U.S. Food and Drug Administration-approved and indicated in the U.S. for the adjunctive long-term treatment of chronic or recurrent depression for patients 18 years of age or older who are experiencing a major depressive episode and have not had an adequate response to four or more adequate antidepressant treatments The most commonly reported side effects are voice alteration or hoarseness, prickling or tingling in the skin, increased coughing, shortness of breath, and sore throat. Infection is the most common complication of the surgical procedure. Important safety information is available at www.livanova.com/depression/en-us/safety-information.

References

  1. Conway CR, et al. Vagus nerve stimulation in treatment-resistant depression: A one-year, randomized, sham-controlled trial. Brain Stimulation. Dec. 18, 2024. DOI: 10.1016/j.brs.2024.12.1191.
  2. The Sheehan Suicidality Tracking Scale (S-STS) is a clinician-administered rating scale that tracks treatment-emergent suicidal ideation and behaviors.
  3. Rush AJ, et al. Effects of vagus nerve stimulation on daily function and quality of life in markedly treatment-resistant major depression: Findings from a one-year, randomized, sham-controlled trial. Brain Stimulation. Dec. 18, 2024. DOI: 10.1016/j.brs.2024.12.1187.
  4. Mini-Q-LES-Q (Quality of Life Enjoyment and Satisfaction Questionnaire – Short Form) is a quality-of-life measure from a self-report assessing the patient’s degree of enjoyment and satisfaction across seven domains as a subset of the Q-LES-Q.
  5. WPAI item 6 is a function measure from the Work Productivity and Activity Impairment (WPAI) Questionnaire.
  6. Q-LES-Q is a quality-of-life measure from a self-report assessing the patient’s degree of enjoyment and satisfaction experienced over the previous seven days across 14 domains.
  7. WHODAS (World Health Organization Disability Assessment Schedule) assesses the patient’s ability to perform activities in the previous month in six domains.
  8. The EuroQoL Five-Dimension Questionnaire (EQ-5D) is a generic QoL measure that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

About LivaNova

LivaNova PLC is a global medical technology company built on nearly five decades of experience and a relentless commitment to provide hope for patients and their families through medical technologies, delivering life-changing solutions in select neurological and cardiac conditions. Headquartered in London, LivaNova employs approximately 2,900 employees and has a presence in more than 100 countries for the benefit of patients, healthcare professionals, and healthcare systems worldwide. For more information, please visit www.livanova.com.

Safe Harbor Statement

This news release contains “forward-looking statements” concerning the Company’s goals, beliefs, expectations, strategies, objectives, plans, underlying assumptions, and other statements that are not necessarily based on historical facts. These statements include, but are not limited to, statements regarding the RECOVER study and the VNS Therapy™ System, Symmetry™. Actual events may differ materially from those indicated in our forward-looking statements as a result of various factors, including those factors set forth in Item 1A of the Company’s most recent Annual Report on Form 10-K, as supplemented by any risk factors contained in Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. LivaNova undertakes no obligation to update the information contained in this press release to reflect subsequently occurring events or circumstances.

LivaNova Investor Relations and Media Contacts



+1 281-895-2382

Briana Gotlin

VP, Investor Relations

InvestorRelations@livanova.com

Deanna Wilke

VP, Corporate Communications

Corporate.Communications@livanova.com

Source: LivaNova PLC

FAQ

What were the key findings of LivaNova's RECOVER study for VNS Therapy (LIVN)?

The study showed statistically significant benefits in secondary endpoints, with improvements in quality of life and daily function, despite not meeting its primary endpoint. Active VNS Therapy demonstrated meaningful therapeutic effects compared to sham treatment.

How many patients participated in the RECOVER study's unipolar cohort for LIVN?

493 adults with treatment-resistant depression participated in the unipolar cohort of the RECOVER study, each having failed more than 13 antidepressant treatments on average.

What were the significant P-values in LivaNova's RECOVER study results?

The study showed significant results with CGI-I (P=0.004) and QIDS-SR (P=0.049) for percentage of time in response, compared with sham VNS Therapy.

When was the RECOVER study completed for LivaNova's VNS Therapy (LIVN)?

The study launched in 2019, completed enrollment in March 2023, and finished the 12-month follow-up in March 2024.

What is LivaNova's next step following the RECOVER study results?

LivaNova plans to submit three additional manuscripts and use the total data from five complementary articles to request coverage from the U.S. Centers for Medicare and Medicaid Services (CMS) for VNS Therapy.

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