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Introduction: Adherence is the extent to which a person’s behavior coincides with health related advice. Poor medication adherence leads to poorer clinical outcomes. TNF-alpha inhibitors (TNF inhibitors) have a significant relationship between clinical outcome and rate of medication adherence. TNF inhibitors are either self-administered (SA) or administered by a healthcare practitioner (HC P-administered), such as a Registered Nurse (RN). To better understand medication adherence in SA and HCP-administered TNF inhibitor populations, an analysis was conducted to measure medication adherence to the HCP-administered product, infliximab, through an alternate site infusion pharmacy. These results were then compared to SA medication adherence rates according to previously published analyses. The comparative results show that administration of infliximab by an RN results in higher medication adherence rates than those reported for SA TNF inhibitor patients. Methods: The analysis was conducted using data extracted from a CPR+ dispensing system, targeting infliximab dispenses with a start of service date (SVC START DT) between 1/1/20 and 8/31/20. Unique patients with at least two SVC START DT values were included. The eligibility of each patient was considered to end as of their final SVC START DT. Adherence was calculated using the industry-standard metric “Proportion of Days Covered” (PDC) methodology. Medication coverage of each treatment was calculated as: Medication Coverage = SVC START DT + Days Supply -1 Adherence was reported as a percentage of analyzed patients with a PDC value of 80% and as the average PDC value of the analyzed population. Results: A 92% average PDC was observed in the overall infliximab RN administered population, with 89% of patients at or above the 80% PDC threshold required to be considered “adherent”. No statistically significant difference in average PDC across age band, sex, or disease state was observed. Conclusion: In this study, patients receiving infliximab administered by an RN (HCP-administered) have a very high adherence rate, as measured by PDC. As it has been reported that patients utilizing SA TNF inhibitors have an average adherence rate of only 37%, these data represent a substantial improvement over SA treatment as it relates to adherence. Additional patient factors not related to the method of administration that could affect adherence including treatment outcomes were not evaluated.Table 1.: Overall Patient Adherence.

Introduction and ObjectiveOnasemnogene abeparvovec (formerly AVXS-101), is designed to address the genetic root cause of spinal muscular atrophy (SMA), survival motor neuron 1 gene (SMN1) deletion/mutation. Here, we evaluate final data from STR1VE-US (NCT03306277), a multicenter, open-label, single-arm, single-dose, Phase 3 study conducted in the United States, investigating efficacy and safety of one-time intravenous infusion of onasemnogene abeparvovec in patients with SMA1 (aged, <6 months).MethodsCo-primary endpoints: independent sitting for ≥30 seconds at the 18 months visit, survival (no death/permanent ventilation) at 14 months of age. Co-secondary endpoints: ability to thrive at 18 months (composite of: tolerates thin liquids, no mechanical nutrition support, maintains weight consistent with age), independence from ventilatory support at 18 months (based on Trilogy BiPAP usage). Safety endpoints: unanticipated treatment-related toxicity of Grade ≥3 based on CTCAE.ResultsAll co-primary and co-secondary endpoints demonstrated statistically significant benefits of onasemnogene abeparvovec compared with untreated controls in the Pediatric Neuromuscular Clinical Research (PNCR) study. Thirteen of 22 (59.1%) patients treated with onasemnogene abeparvovec achieved the milestone of functional independent sitting for ≥30 seconds at the 18-month visit (P<0.0001 vs PNCR). Twenty-one of 22 patients (95.5%) survived ≥10.5 months without permanent ventilatory support and 20/22 (90.9%) patients were surviving free of permanent ventilation at 14 months and 18 months of age. For comparison, the relevant PNCR dataset showed event-free survival of 50% at 10.5 months and 25% at 13.6 months. Nine of 22 (40.9%) patients maintained the ability to thrive at 18 months of age, 15/22 (68.2%) patients received no non-oral feeding support at any time during the study, and 18/22 (81.8%) patients were independent of ventilator support at 18 months of age based on Trilogy BiPAP data. Patients exhibited rapid (1-month post doing) and sustained improvements in motor function (CHOP INTEND scores) and achieved motor milestones, previously unseen in PNCR dataset. Adverse events were manageable and consistent with the known safety profile of onasemnogene abeparvovec.ConclusionsIn the STR1VE-US study, patients with SMA1 treated with onasemnogene abeparvovec demonstrated a significant therapeutic benefit and a favourable the benefit-risk profile.

Patients with primary immunodeficiency diseases often require lifelong immunoglobulin (IG) therapy. Most clinical trials investigating IG therapies characterize serum immunoglobulin G (IgG) pharmacokinetic (PK) profiles by serially assessing serum IgG levels. This retrospective analysis evaluated whether steady-state serum IgG trough level measurement alone is adequate for PK assessment. Based on individual patient serum IgG trough levels from two pivotal trials (phase 2/3 European [NCT01412385] and North American [NCT01218438]) of weekly 20% subcutaneous IG (SCIG; Cuvitru, Ig20Gly), trough level-predicted IgG AUC (AUCτ,tp) were calculated and compared with the reported AUC calculated from serum IgG concentration-time profiles (AUCτ). In both studies, mean AUCτ,tp values for Ig20Gly were essentially equivalent to AUCτ with point estimates of geometric mean ratio (GMR) of AUCτ,tp/AUCτ near 1.0 and 90% CIs within 0.80–1.25. In contrast, for IVIG, 10%, mean AUCτ,tp values were lower than AUCτ by >20%, (GMR [90% CI]: 0.74 [0.70–0.78] and 0.77 [0.73–0.81] for the two studies, respectively). Mean AUCτ,tp values calculated for 4 other SCIG products (based on mean IgG trough levels reported in the literature/labels) were also essentially equivalent to the reported AUCτ (differences <10% for all except HyQvia, a facilitated SCIG product), while differences for IVIG products were >20%. In conclusion, steady-state serum IgG levels following weekly SCIG remain stable, allowing for reliable prediction of AUC over the dosing interval using trough IgG levels. These findings indicate that measuring steady-state serum IgG trough levels alone may be adequate for PK assessment of weekly SCIG.

BackgroundObjective symptom monitoring of patients with Amyotrophic Lateral Sclerosis (ALS) has the potential to provide an important source of information to evaluate the impact of the disease on aspects of real-world functional capacity and activities of daily living in the home setting, providing useful objective outcome measures for clinical trials.ObjectiveThis study aimed to investigate the feasibility of a novel digital platform for remote data collection of multiple symptoms—physical activity, heart rate variability (HRV), and digital speech characteristics—in 25 patients with ALS in an observational clinical trial setting to explore the impact of the devices on patients’ everyday life and to record tolerability related to the devices and study procedures over 48 weeks.MethodsIn this exploratory, noncontrolled, nondrug study, patients attended a clinical site visit every 3 months to perform activity reference tasks while wearing a sensor, to conduct digital speech tests and for conventional ALS monitoring. In addition, patients wore the sensor in their daily life for approximately 3 days every month for the duration of the study.ResultsThe amount and quality of digital speech data captured at the clinical sites were as intended, and there were no significant issues. All the home monitoring sensor data available were propagated through the system and were received as expected. However, the amount and quality of physical activity home monitoring data were lower than anticipated. A total of 3 or more days (or partial days) of data were recorded for 65% of protocol time points, with no data collected for 24% of time points. At baseline, 24 of 25 patients provided data, reduced to 13 of 18 patients at Week 48. Lower-than-expected quality HRV data were obtained, likely because of poor contact between the sensor and the skin. In total, 6 of 25 patients had mild or moderate adverse events (AEs) in the skin and subcutaneous tissue disorders category because of skin irritation caused by the electrode patch. There were no reports of serious AEs or deaths. Most patients found the sensor comfortable, with no or minimal impact on daily activities.ConclusionsThe platform can measure physical activity in patients with ALS in their home environment; patients used the equipment successfully, and it was generally well tolerated. The quantity of home monitoring physical activity data was lower than expected, although it was sufficient to allow investigation of novel physical activity end points. Good-quality in-clinic speech data were successfully captured for analysis. Future studies using objective patient monitoring approaches, combined with the most current technological advances, may be useful to elucidate novel digital biomarkers of disease progression.