Novartis (United States)

To evaluate the association of hyperreflective foci contiguous with the retinal pigment epithelium (rpeHRF) with visual function impairment in aged normals, early age-related macular degeneration (eAMD), and intermediate AMD (iAMD). Prospective cohort study. Participants of the MACUSTAR study. MACUSTAR participants underwent color fundus photography, optical coherence tomography (OCT) imaging, best corrected visual acuity (BCVA), low-luminance VA (LLVA), rod-mediated dark adaptation (RMDA) at 12°, contrast sensitivity (CS), mesopic (mesPSD), and scotopic pointwise sensitivity deviation (scPSD) testing. rpeHRF presence and count were determined using custom FiJi software. Group comparisons and associations with visual function were analyzed using analysis of variance, linear regression, and Spearman correlation. Presence, burden, and topographic distribution of rpeHRF, as well as association with functional parameters, were determined. Fifty-six normal aged (33 female, mean age 68.1 ± 6.4 years), 34 eAMD (27 female, 71.7 ± 6.4 years), and 583 iAMD eyes (387 female, 72.0 ± 7.0 years) were included. rpeHRF counts were 0.16 ± 0.85 in normals, 0.33 ± 0.96 in eAMD, and 1.61 ± 2.49 in iAMD (P < .001). BCVA, LLVA, CS (all P < .001), and scPSD (P = .001) differed between disease groups, whereas RMDA and mesPSD did not. In iAMD, eyes with rpeHRF showed worse BCVA, LLVA, CS, scPSD (all P < .001), and mesPSD (P = .02). rpeHRF was found to be associated modestly with only CS, scPSD, LLVA, and BCVA. Presence and burden of rpeHRF were independently associated with impaired visual function and may thus serve as a prognostic biomarker for disease progression and enrichment criterion for future interventional trials.

Spondyloarthritis (SpA), including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), comprises a diverse but interrelated family of inflammatory diseases characterized by inflammation of the joints and spine. Signs and symptoms of SpA vary widely, as patients experience a diverse spectrum of musculoskeletal and extra-musculoskeletal disease manifestations. Interleukin (IL)-17 is an inflammatory cytokine common to the pathogenesis of SpA disease development and progression. The IL-17A inhibitor secukinumab has been well established in clinical trials and real-world practice as an effective therapeutic tool to efficiently manage SpA indications axSpA and PsA in adults, as well as juvenile PsA (jPsA) and enthesitis-related arthritis (ERA), which are two subtypes of juvenile idiopathic arthritis. This review highlights the comprehensive response to IL-17 inhibition with secukinumab across SpA indications of PsA, axSpA, and ERA/jPsA and within each indication according to established disease domains. We provide context through expert commentary on the effect of inhibiting IL-17 with secukinumab on the full spectrum of SpA disease manifestations, as well as areas in need of further investigation.

Objective To inform potential negotiations under the Medicare Drug Price Negotiation Program, this study evaluates the cost-effectiveness of ribociclib versus palbociclib as first-line (1 L) treatment for patients with HR+/HER2– advanced breast cancer (aBC) from the Medicare perspective. Methods A three-way partitioned survival model with states defined by progression-free survival (PFS) and overall survival (OS) was estimated over a lifetime horizon with a 28-day cycle length using data from Phase III MONALEESA-2 (ribociclib) and PALOMA-2 (palbociclib) trials. Relative treatment efficacy was measured using PFS and OS HRs derived from an anchored matching adjusted indirect comparison. Incremental cost-effectiveness ratios (ICERs) were calculated with costs estimated from a Medicare perspective and effectiveness measured using quality adjusted life years (QALYs), life years (LYs), progression-free life years (PFLYs), equal value life years (evLYs), and health years in total (HYT). All effectiveness and cost measures were discounted at 3%. A willingness-to-pay (WTP) threshold of $150,000 per QALY/evLY was used to assess cost-effectiveness. Results Measures of effectiveness consistently favoured ribociclib with estimated gains of 1.40 QALYs, 1.83 LYs, 1.08 PFLYs, 1.59 evLYs, and 1.80 HYT relative to palbociclib. Total costs were comparable, with ribociclib associated with a marginal 1.8% lifetime cost increase. ICERs ranged from $4,697 per LY gained to $7,973 per PFLY gained. At a WTP threshold of $150,000 per evLY, ribociclib demonstrated an approximately 100% probability of being cost-effective relative to palbociclib. Conclusion Ribociclib improved health outcomes with a minimal relative cost increase and is therefore a highly cost-effective 1 L treatment option vs. palbociclib in patients with HR+/HER2– aBC from the Medicare perspective.

Intrathecal onasemnogene abeparvovec (OAV101 IT) may enable a one-time gene transfer therapy, addressing an unmet need across the broader spinal muscular atrophy (SMA) population. STRENGTH ( NCT05386680 ) was a 52-week, phase 3b, single-arm, open-label, multicenter study evaluating OAV101 IT in participants with SMA aged 2 to <18 years who discontinued nusinersen or risdiplam. The primary objective was safety/tolerability. Twenty-seven participants were enrolled (mean (s.d.) age at OAV101 IT, 7.4 (3.35) years; range, 2.4-17.7 years) with prior nusinersen or risdiplam (mean (s.d.) duration of 4.3 (1.07) years; range, 1.86-6.18 years or 3.0 (2.02); range, 0.39-6.28 years). All (n = 27) experienced at least one adverse event (AE), most frequently nasopharyngitis (n = 15, 55.6%), pyrexia (n = 14, 51.9%) and vomiting (n = 13, 48.1%). Thirteen participants (48.1%) experienced treatment-related AEs, most frequently vomiting (n = 6, 22.2%), headache (n = 4, 14.8%) and pyrexia (n = 3, 11.1%). Serious adverse events (SAEs) were reported for four participants (n = 4, 14.8%) (mostly respiratory infection related). No AEs leading to death or study discontinuation were reported. Adverse events of special interest (AESI) reported were in categories of transient thrombocytopenia (n = 8, 29.6%), hepatotoxicity (n = 4, 14.8%) and signs and symptoms that may be suggestive of dorsal root ganglia toxicity (n = 2, 7.4%). The OAV101 IT safety profile was consistent with findings in treatment-naïve patients. Trial registration: ClinicalTrials.gov identifier: NCT05386680 .

Objective This study aims to evaluate the cost-effectiveness of ribociclib versus abemaciclib as first-line (1 L) treatment among women with HR+/HER2– advanced breast cancer (aBC) from a Medicare perspective. Methods Using data from the MONALEESA-2 (ribociclib) and MONARCH 3 (abemaciclib) clinical trials and other sources, a partitioned survival model with states defined by progression-free survival (PFS) and overall survival (OS) was estimated over a lifetime horizon with a 28-day cycle length. Relative treatment efficacy was measured using PFS and OS HRs derived through an anchored matching adjusted indirect comparison. Incremental cost-effectiveness ratios (ICERs) were calculated with costs estimated from a Medicare perspective and effectiveness measured in terms of quality-adjusted life years (QALYs), life years (LYs), progression-free life years (PFLYs), equal value life years (evLYs), and health years in total (HYT). All measures of effectiveness and cost were discounted at 3%. A willingness-to-pay (WTP) threshold of $150,000 per QALY/evLY was used to evaluate cost-effectiveness. Results Measures of effectiveness were consistently higher for ribociclib versus abemaciclib with gains in QALYs (+0.81), LYs (+1.05), PFLYs (+0.65), evLYs (+0.93), and HYT (+1.05). Total costs to Medicare were 14.7% higher with ribociclib vs. abemaciclib ($487,715 vs $425,198, respectively). Ribociclib was cost-effective versus abemaciclib with estimated ICERs of $77,199 per QALY, $59,320 per LY, $96,829 per PFLY, $67,210 per evLY, and $59,624 per HYT gained. At a WTP threshold of $150,000 per evLY, the probability that ribociclib is cost-effective versus abemaciclib, which was 81%. Conclusion Ribociclib improves health outcomes with a modest impact on costs and is likely to be more cost-effective than abemaciclib for postmenopausal women requiring 1 L treatment of HR+/HER2– aBC from a Medicare perspective.

Atherosclerotic cardiovascular disease (ASCVD) is a global health concern. Reducing low-density lipoprotein cholesterol (LDL-C) is critical in ASCVD prevention and treatment. Inclisiran, a novel RNA therapeutic agent, offers a promising solution by lowering LDL-C with twice-yearly dosing after an initial and 3-month dose. The study objective was to evaluate adherence to inclisiran and its lipid-lowering effectiveness over a year of treatment. This retrospective cohort study involved patients over 18 years old with ASCVD or hyperlipidemia who initiated inclisiran between January 1, 2022, and May 17, 2023, in US outpatient clinics. LDL-C reduction was evaluated in patients with ≥ 1 pre- and post-index LDL-C measurement by comparing baseline levels to the lowest value within 12 months after initiating inclisiran. Overall, 225 patients initiated inclisiran. The mean age was 69.9 years and 50.7% were female. Most patients (81.8%) had ASCVD. Most patients (91.6%) received a second dose, and 84.5% of these received a third dose. Overall, 202 patients had ≥ 2 LDL-C measurements, with a mean baseline LDL-C of 134.8 mg/dl. Mean absolute LDL-C reduction was 66.1 (standard deviation: 45.6) mg/dl, corresponding to a 46.8% (95% confidence interval: 42.7-51.0) relative reduction, and 46.8% achieved ≥ 50% reduction. Patients on concurrent statins and those without prior anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibodies experienced the largest relative LDL-C reductions: 55.4% and 51.1%, respectively. Inclisiran significantly reduced LDL-C. The dosing schedule promoted high adherence in a real-world setting, particularly among older adults with ASCVD. These findings indicate inclisiran may be a particularly valuable addition to lipid-lowering strategies.

Chikungunya virus (CHIKV) causes periodic outbreaks and is endemic in more than 110 countries. VIMKUNYA, a CHIKV virus-like particle (CHIKV VLP) vaccine, was recently approved by regulators in the United States, European Union, and United Kingdom. Efficacy of VIMKUNYA in endemic settings is difficult to evaluate due to outbreak unpredictability. We used cynomolgus macaques, which model human CHIKV viremia and disease, to assess CHIKV VLP vaccine efficacy. Doses as low as 1.25 mg of CHIKV VLP with aluminum hydroxide adjuvant and passively transferred IgG from vaccinated humans significantly reduced viremia, disease, and joint pathology. Despite having IgG doses yielding neutralizing titers below the established predicted protective threshold of ≥100, animals fared better than the CHIKV-infected control animals, suggesting clinical benefits may occur at lower antibody levels. These findings demonstrate immunogenicity and protective efficacy of CHIKV VLP and relevance of neutralizing antibodies in protection, reinforcing its use in humans to protect against chikungunya disease.