Bristol-Myers Squibb (United Kingdom)

In the phase 2, double-blind, randomized controlled BEYOND trial (NCT03342404), luspatercept increased hemoglobin levels in patients with non-transfusion-dependent β-thalassemia (NTDT). This study assessed long-term effects of luspatercept on patient-reported outcomes (PROs), using data from BEYOND and patients who continued luspatercept treatment in the phase 3b long-term follow-up (LTFU) study (NCT04064060). In BEYOND, patients received luspatercept or placebo Q3W for ≥ 48 weeks. PRO instruments included NTDT-PRO (BEYOND only), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and 36-Item Short Form Survey (SF-36). Mixed-effects models with repeated measures estimated least squares mean changes from baseline in PROs. PROs were evaluable in 144 patients (luspatercept 95, placebo 49) from BEYOND and 58 (luspatercept) from LTFU. Luspatercept improved NTDT-PRO tiredness/weakness and shortness of breath domain, FACIT-F fatigue subscale, and SF-36 vitality scores versus placebo through double-blind treatment (generally maintained through week 96). In LTFU patients, significant, meaningful improvements from baseline in FACIT-F fatigue subscale and SF-36 vitality scores were observed within 12 weeks of treatment initiation and maintained for up to 5 years. Other FACIT-F and SF-36 domains improved or were maintained throughout LTFU. Luspatercept offers rapid and durable benefits by improving anemia-related symptoms and quality of life in patients with NTDT. Trial Registration: ClinicalTrials.gov Identifier: NCT03342404; NCT04064060.

<h2>Abstract</h2><h3>Background</h3> There is limited real-world data on the demographic and clinical characteristics of adult patients with obstructive hypertrophic cardiomyopathy (oHCM) treated with mavacamten in Canada. <h3>Methods</h3> This was an observational retrospective cohort study on adult patients with symptomatic oHCM enrolled in the mavacamten Patient Support Program (PSP) in Canada between January 4, 2023, and April 12, 2024. Baseline demographic information, clinical characteristics, medical history, and mavacamten treatment information were collected from the PSP database. <h3>Results</h3> A total of 683 patients met the eligibility criteria for the study. The median age was 65.0 years (IQR: 57.0-73.0), 52.1% of the patients were male, and 67.1% were classified as NYHA class II at baseline. Most patients were on beta blocker monotherapy at baseline (63.7%) and data cut-off (76.3%). Almost all patients (99.4%) were initiated with 5 mg of mavacamten. The median follow-up time was 27.4 weeks (range: 1.6-70.1), and the median treatment duration was 24.6 weeks (range: 0.4-64.4). At data cut-off, 17.1% of patients were on 2.5 mg of mavacamten, 52.6% were on 5 mg, 20.2% were on 10 mg, and 2.2% were on 15 mg. Mavacamten was discontinued by 7.9% of patients, with the main reasons being side effect or adverse event (2.5%; 17/683), undisclosed physician decision (1.8%; 12/683), or lack of efficacy (0.9%; 6/683). <h3>Conclusions</h3> These early results provide the largest dataset on mavacamten utilization in the Canadian oHCM population. Baseline demographic and clinical characteristics and mavacamten dose distributions are comparable to findings from clinical trials and real-world studies. NCT06549608.

The objective of this study was to assess the cost-effectiveness of mavacamten in combination with the standard of care (SoC), composed of beta-blockers and calcium channel blocker monotherapy, compared to the SoC alone in the treatment of patients with obstructive hypertrophic cardiomyopathy with persistent symptoms, from a French collective perspective. A four state Markov model defined by NYHA classification levels I to III/IV and death was developed to simulate the evolution of disease severity over a lifetime horizon. Clinical inputs and utilities were derived from EXPLORER-HCM trial. According to HAS recommendations, costs, life-years (LYs) and quality-adjusted LYs (QALYs) per patient, incremental costs and LYs/QALYs, incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) were estimated. Model uncertainty was assessed through deterministic, probabilistic sensitivity analyses and scenario analyses. Mavacamten in combination with SoC was associated with a QALY gain of 1.52, driven by an improved NYHA distribution of mavacamten patients. Incremental discounted costs were €122,651, owing to increased treatment acquisition costs, partly offset by savings in healthcare resource utilization, resulting in an ICUR of €80,799/QALY. The sensitivity analyses showed the results of the model were relatively robust. The probabilistic sensitivity analysis confirmed base-case ICUR, with 80% probability of mavacamten being cost effective at a willingness-to-pay of €93,750/QALY. The scenario analysis simulating a limited societal perspective highlighted the potential benefit of mavacamten treatment on productivity loss costs. On a public list price basis, mavacamten in combination with SoC is a cost-effective strategy for symptomatic obstructive HCM compared to SoC alone.

This article is part of our ‘Rising Stars’ series, giving a platform to the emerging leaders of the sector. In this series, we share the perspectives of fledgling thought-leaders, chosen by our Editorial Advisory Board members as future stars in their field. John Moscariello, Chief Technical Officer at Neuvogen Therapeutics, had this to say about his Rising Star nominee: 'Almost immediately upon the approval of the first gene-modified cell therapy products, process developers asked how we can make the product cheaper. While this emphasis has led to significant advances in automation, many people have missed what I think is a more impactful question—how can we make products with better clinical outcomes? Sarah Rajani is the industry-leader in developing adaptive cell therapy processes in which real-time measurements of cell attributes can be used to change process conditions.'

ABSTRACT EVIDENS was a prospective, non-interventional, longitudinal study conducted in non-small cell lung cancer (NSCLC) patients receiving nivolumab in France. It recruited adults with pathologically confirmed NSCLC who initiated nivolumab between October 2016 and November 2017; the final results are reported here. Primary outcomes included baseline characteristics and 36-month overall survival (OS). Secondary outcomes included progression free survival (PFS), objective response rate (ORR), safety and health-related quality of life (HRQoL; assessed regardless of nivolumab continuation or interruption). Overall, 1423 patients were included in the analysis population (median age 66 years; non-squamous histology 69.1%; stage IV disease 91.5%; brain metastases 19.9%). Almost all patients (99.7%) had received prior chemotherapy, and most patients received nivolumab as second-line (73.5%) or later (26.1%) therapy. The 36-month OS rate was 19.7% (95% confidence interval [CI] 17.5–22.0); OS was significantly shorter in patients with squamous versus non-squamous tumors (9.8 [95% CI 8.6–11.2] months vs 11.8 [95% CI 10.2–13.2] months; p = 0.005). The 36-month PFS rate was 8.8% (95% CI 7.3–10.4). The 12-month investigator-assessed best ORR in the overall population was 20.4%. Eastern Cooperative Oncology Group performance status, smoking status, tumor histology, disease stage and liver metastasis independently predicted survival. Grade 3 and 4 treatment-related adverse events were reported in 8.0% and 0.8% of patients, respectively; eight treatment-related deaths occurred (0.005%). HRQoL was maintained with slight improvement throughout the study, without statistical significance. These results confirm that the real-world effectiveness and safety of nivolumab in these patients is similar to that observed in clinical trials.