UCB Pharma (Germany)

Access to cross-border clinical trials may represent the sole therapeutic option for children living with rare diseases for which no approved medicines exist. Many children are excluded from participation in trials due to language restrictions. There are insufficient comprehensive analyses of the experiences and preferences of parents across Europe concerning participation and exclusion of their child in international clinical trials, particularly regarding language support during enrollment in cross-border clinical research studies. An anonymous online survey was designed and translated into 22 official European languages to collect data from parents of children living with a disease across Europe. The survey included five sections: (1) sociodemographic information; (2) experience participating in a clinical trial; (3) experience in cases where the patient was unable to take part in a study abroad; (4) experience participating in a clinical trial abroad; and (5) preferences regarding decentralized trial options. 1,436 responses were analyzed from parents across 34 European countries. 55.7% of the parents reported being able to communicate in English. 10.7% had prior clinical trial experience, of whom 30.1% traveled abroad to enable their child to participate. Among those reporting being excluded from cross-border trials, 34.7% cited language barriers or country of residence as the reason. Most families expressed a strong willingness to accept decentralized trial options, regardless of where the study may be conducted. Accommodating language translation to permit participation in a clinical trial abroad is feasible. While a significant percentage of caregivers of pediatric patients in Europe could communicate in English, approximately one-third of those excluded from clinical trials cited language barriers or country of residence as the reason. When translation was required, the most commonly offered solution was the use of professional interpreters, an accommodation that could enable broader patient participation in essential research.

a:2:{s:4:"lang";s:2:"en";s:7:"content";s:1580:"<h3>Background</h3> In MycarinG (NCT03971422; Phase 3), adults with generalised myasthenia gravis (gMG) received one 6-week rozanolixizumab treatment cycle. All patients who enrolled in MG0007 (NCT04650854; open-label extension) received one further treatment cycle with subsequent need-based cycles initiated at the investigator’s discretion. Thus, cycle number and treatment-free intervals varied per patient. <h3>Methods</h3> Clustering analysis was conducted on the number of cycles per year (CPY) in patients with ≥1 cycle from MycarinG and MG0007 (data cut-off: 08 July 2022). Baseline characteristics were assessed for association with CPY using multivariate regression models. Treatment-emergent adverse events were compared among clusters. <h3>Results</h3> Balanced clustering and optimal goodness-of-fit was achieved using three clusters to describe CPY (low: &lt;2.59; medium: 2.59–4.64; high: &gt;4.64). Mean (standard deviation) CPY in each cluster was 1.50 (0.53, n=74), 3.59 (0.60, n=64) and 5.82 (0.72, n=50), respectively. Overall, baseline characteristics were balanced between clusters and were not predictive of CPY for patients. Rozanolixizumab was generally well tolerated across the clusters. <h3>Conclusions</h3> These three treatment clusters demonstrate that rozanolixizumab cycle cadence varies between patients, from 1–7 CPY. This suggests an individualised approach to rozanolixizumab treatment based on each patient’s own gMG experience, as the study included a broad, adult gMG population. rowan.orme{at}ucb.com ";}

resulting in patients being wrongly allocated to a worse DAPSA disease state.This error impacted two rows in Table 2.

Overexpression of interleukin (IL)-17A and IL-17F significantly influences psoriasis pathology. Until recently, biologics targeting IL-17A alone, like secukinumab, were used to treat psoriasis. Bimekizumab is a monoclonal IgG1 antibody that targets both IL-17A and IL-17F. BE RADIANT was the first phase III trial to investigate switching from selective inhibition of IL-17A to dual inhibition of IL-17A and IL-17F. Bimekizumab has previously shown superior achievement of complete skin clearance [100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100)] vs. secukinumab through 48 weeks. Switching from secukinumab to bimekizumab resulted in improved clinical responses. Over 2 years, no new safety signals were observed. To report the 3-year efficacy and safety of bimekizumab in patients with moderate-to-severe plaque psoriasis receiving continuous bimekizumab or switching from secukinumab after 1 year. The BE RADIANT phase IIIb randomized controlled trial had a 48-week double-blinded period, in which patients received bimekizumab [320 mg every 4 weeks (Q4W)] or secukinumab (300 mg weekly to week 4, then Q4W). At week 16, patients randomized to bimekizumab underwent re-randomization to receive Q4W or Q8W maintenance dosing. From week 48 onward (open-label extension), all received bimekizumab. In total, 336 patients randomized to bimekizumab and 318 randomized to secukinumab at baseline entered the open-label extension. More patients randomized to bimekizumab achieved PASI 100 (modified nonresponder imputation) at year 1 (74.9%) vs. those randomized to secukinumab (52.8%). PASI 100 response rates were maintained over 3 years in patients treated with bimekizumab (68.8%) and increased in those randomized to secukinumab switching to bimekizumab (68.8%). Bimekizumab was well tolerated to 3 years. In patients who received ≥ 1 bimekizumab dose, the most common treatment-emergent adverse events (TEAEs) over 3 years were nasopharyngitis, oral candidiasis and upper respiratory tract infection (exposure-adjusted incidence rates 12.2, 10.0 and 5.5/100 patient-years, respectively). Rates of TEAEs of interest, including serious infections, inflammatory bowel disease, and suicidal ideation and behaviour, did not increase with longer exposure to bimekizumab from 1 to 3 years. More than two-thirds of patients randomized to bimekizumab and those who switched from secukinumab to bimekizumab achieved and maintained complete skin clearance over 3 years of treatment. Over 3 years, bimekizumab was well tolerated and TEAE rates did not increase with longer exposure. NCT03536884.

Abstract BackgroundAlzheimer’s disease neuropathology involves the deposition in brain of aggregates enriched with microtubule‐binding‐region (MTBR) of tau adopting an abnormal conformation between residues 306‐378 in the core of aggregates. Anti‐tau drugs targeting around this domain have the potential to interfere with the cell‐to‐cell propagation of pathological tau. Bepranemab is a humanized monoclonal Ig4 antibody binding to tau residues 235‐250. Previous studies showed this antibody binds to tau monomers; inhibits tau seeding in cellular assay and prevents tau pathology spread in a mouse model. The target engagement of bepranemab in human biofluids is unknown. This study aims to characterize cerebrospinal fluid (CSF) tau species binding to this antibody.MethodsWe used mass spectrometry (MS) to characterize CSF tau species precipitating with bepranemab cross‐linked to sepharose beads. Precipitated CSF tau species were digested with trypsin and tau peptides were quantified by signal comparison to peptides from tau labeled standard. We characterized and compared the amount of bepranemab‐reactive tau species recovered from neat CSF and from CSF initially depleted from N‐terminal and Mid‐domain truncated tau species. Then, we analyzed Bepranemab precipitates in CSF samples from 14 asymptomatic dominantly inherited Alzheimer’s disease (DIAD) mutation carriers (aMC), 16 symptomatic (sMC) and 15 non‐carriers (NC).ResultsBepranemab bound to a mixture of CSF N‐terminal and Mid‐domain tau‐truncated fragments including mainly 226‐254 tau residues on their C‐terminal domain (Figure 1). Bepranemab‐reactive species not containing the N‐ter and the Mid‐domain of tau were mostly comprised of fragments including tau residues 226 to 267. Minor bepranemab‐reactive tau species contained tau residues 275 to 290 on their C‐terminal. Tau peptides after residues 317 were not detected above the MS limit of detection. In DIAD, the pool of bepranemab‐immunoreactive CSF tau fragments significantly increased in asymptomatic and symptomatic mutations carriers respectively (Figure 2).ConclusionsThe pool of CSF tau species included a subset of tau MTBR‐containing fragments recovered by bepranemab. A minor fraction of these fragments had domains overlapping with the upstream domain constituting the AD tau aggregate core. These fragments increased over DIAD stages. Our study supports bepranemab engagement against a specific pool of tau species in CSF. This work was sponsored by UCB.

ObjectiveEfficacy, tolerability, and behavioral/executive functioning during long-term adjunctive brivaracetam treatment were assessed in pediatric patients with focal-onset seizures (FOS) with/without cognitive/learning comorbidities (CLC). MethodsPost hoc analysis of a phase 3 open-label follow-up trial (N01266/NCT01364597). Patients with FOS (<16 years at core trial entry; direct enrollers ≥4–<17 years) received ≤5 mg/kg/day brivaracetam (≤200 mg/day). Subgroup analyses were performed for patients with and without ongoing CLC at baseline. ResultsPatients with CLC (84/185 [45.4 %]) had longer epilepsy duration and higher number of prior antiseizure medications. Kaplan-Meier–estimated brivaracetam retention at 1, 3, and 5 years was 75.0 %/78.2 %, 61.9 %/61.9 %, and 52.2 %/53.3 % in patients with/without CLC. Efficacy assessments (patients >2 years of age) showed numerically lower median percent reduction in FOS frequency/28 days (43.8 %/74.1 % [n = 63/60]), 50 % responder rates for FOS (46.0 %/61.7 % [n = 63/60]), and ≥12-month continuous freedom from all seizures (31.7 %/55.9 % [n = 60/68 patients with ≥12 months treatment]) in patients with/without CLC. Treatment-emergent adverse events were reported in 94.0 %/95.0 % of patients with/without CLC (serious: 33.3 %/27.7 %; drug-related: 31.0 %/33.7 %). From baseline to last evaluation, most patients with/without CLC had no shift in T-score category for each Achenbach Child Behavior Checklist (CBCL) 1.5–5 syndrome (≥50.0 %/≥72.2 %), CBCL 6–18 syndrome (≥66.0 %/≥69.1 %), and Behavior Rating Inventory of Executive Function scale (≥66.7 %/≥69.0 %). ConclusionsThese data indicate that brivaracetam could be an efficacious and well-tolerated treatment option for pediatric patients with FOS with and without CLC. Behavior and executive functioning were generally stable or slightly improved in patients with and without CLC.

Introduction: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease which significantly impacts health-related quality of life.1 Bimekizumab (BKZ) is a humanized IgG1 monoclonal antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A.2 ere, the cumulative benefit of BKZ treatment on HS clinical response (HiSCR) through 16 and 48 weeks (wks) is reported using area under the curve (AUC) analyses.Procedure/study: Pooled data from BE HEARD I&amp;II included an initial (Wks0–16) and maintenance treatment period (Wks16–48).3 Randomization: 2:2:2:1 (initial/maintenance) BKZ 320mg every 2 wks (Q2W)/Q2W, BKZ Q2W/Q4W, BKZ Q4W/Q4W, or placebo (PBO)/BKZ Q2W. HiSCR50/75/90 response was achieved at a given visit if there was ≥50/75/90% reduction in the total abscess/inflammatory nodule count with no increase from baseline in abscess or draining tunnel count. Cumulative clinical benefit estimation: total AUC through Wk48 for HiSCR50/75/90 achievers. Calculation of estimated number of days patients achieved each response: proportion of total possible AUC for each outcome multiplied by total number of days in the period (Wks0–16: 112 days, Wks0–48: 336). Data are reported as observed case, where N represents number of patients with a non-missing lesion count assessment in the given week, and percentages are calculated accordingly (i.e. where data recorded after an intercurrent event are included).Results: Overall, 1,014 patients were randomized to BKZ Q2W/Q2W (N=288), BKZ Q2W/Q4W (N=292), BKZ Q4W/Q4W (N=288) and PBO/BKZ Q2W (N=146). Through 16wks, the total number of days patients achieved HiSCR50 was almost double in BKZ Q2W/Q2W (47 days), BKZ Q2W/Q4W (49), and BKZ Q4W/Q4W (47) groups vs PBO (27). To Wk16, the total number of days patients achieved HiSCR75/90 was at least double in the BKZ groups vs PBO. To Wk48, total number of days with HiSCR50 achievement: BKZ Q2W/Q2W, 211; BKZ Q2W/Q4W, 212; BKZ Q4W/Q4W, 206 vs PBO/BKZ Q2W, 178. Comparable results were observed for HiSCR75/90 at Wk48, with BKZ groups maintaining higher responses vs PBO. Conclusion: High levels of cumulative clinical benefit were observed for patients on BKZ through Wk16; benefits increased substantially through Wk48. The cumulative benefit of BKZ through 48wks was evident for patients receiving continuous BKZ and PBO switchers. The total number of days of clinical outcome achievement remained higher in those on continuous BKZ vs PBO switchers. These results demonstrate the rapid, high-level and durable responses that can be obtained with BKZ.

The objective of this study is to evaluate possible long-term effects of treatment with brivaracetam (BRV) on body weight in children with epilepsy. Post hoc analysis of data from patients (aged 1 month to <17 years) with ≥6 months of BRV treatment in a long-term, open-label trial (N01266 [NCT01364597]). Outcomes included body weight and body mass index (BMI) over time (z-score growth curves), and treatment-emergent adverse events (TEAEs). Previous/ongoing medical conditions that may affect body weight (gastrointestinal and metabolic/nutritional disorders); concomitant antiseizure medications (ASMs) were also evaluated. Two hundred nine patients (mean [standard deviation] age 7.9 [4.6] years) were analyzed. Most (154 [73.7%]) had focal-onset seizures. At study initiation, median (range) BRV dose was 1.0 (0.4-7.5) mg/kg/day. Overall, 189 (90.4%) patients had a previous or ongoing medical condition (gastrointestinal disorders: 43 [20.6%]; metabolism/nutritional disorders: 26 [12.4%]). Most patients followed z-score curves for body weight and BMI during BRV treatment, although there were outliers in both directions. Incidences of appetite/weight-change TEAEs were low. Twenty-three (11.0%) patients had a TEAE of decreased appetite and 14 (6.7%) had a TEAE of weight decreased. Long-term adjunctive BRV was well tolerated in growing children with no indication of detrimental effects on body weight. Brivaracetam is an antiseizure medication (ASM) used to treat seizures in people with epilepsy. Some ASMs can lead to changes in people's appetite and weight. Knowing the effect a drug has on appetite and weight is particularly important in children. We looked at 209 children with epilepsy taking brivaracetam and studied changes in their body weight and body mass index over time. The number of reported side effects related to appetite or weight change was low. There was no apparent long-term effect on their body weight, even when taking their medical history and use of other ASMs into account.