Lilly (China)

BackgroundWe aimed to describe the diagnostic journey, current treatment, caregiving needs, and burden of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia in China.MethodData were drawn from the Adelphi Real World AD Disease Specific Programme™, a cross‐sectional survey of neurologists and their patients with MCI/AD across China, between 2024/02–2024/05. Neurologists completed patient record forms for their next (up to) nine consecutively consulting MCI/AD patients, capturing the diagnostic journey, current treatment, and caregiver support. Patients were invited to provide a self‐completion questionnaire, reporting on delays to first seeing a doctor and quality of life via the EQ‐5D visual analogue scale. Disease severity was defined using Mini Mental State Examination (MMSE) score: MCI/mild AD (20‐28) or moderate/severe AD (0‐19). Analyses were descriptive.ResultNinety‐three neurologists reported data on 774 patients (mean±standard deviation age 69.2±8.3 years, body weight 64.2±11.4 kg, 49.1% female), of whom 192 self‐completed a patient survey. Of 699 patients with an available MMSE, 52.5% were currently MCI/mild AD and 47.5% moderate/severe AD. Median (interquartile range [IQR]) time between symptom onset and first consultation was 18.1 (8.4, 40.3) weeks, with 34.7% of patients experiencing moderate/severe AD by their initial consultation. Most patients (80.0%) were not diagnosed at initial consultation, with median (IQR) time from first consultation to diagnosis taking 4.4 (1.9, 12.9) weeks. Few patients (18.8%) had a biomarker confirmed diagnosis (mainly cerebral spinal fluid [11.2%] and amyloid positron emission tomography [7.7%]). Acetylcholinesterase Inhibitors (66.0%), N‐methyl‐D‐aspartate antagonist (33.5%), and nootropics (26.4%) were the most common current treatments, and long‐lasting effect was the top (37.1%) identified area for improvement. Among those with MCI/mild AD, 79.4% received non‐professional care (NPC) and 2.7% required professional care (95.2% and 15.7% for moderate/severe AD, respectively). On average, NPC partners spent 36.7±39.5 hours/week for MCI/mild AD and 47.3±39.6 hours/week for moderate/severe AD, and spouse/partner was the most frequent NPC partner. Mean EQ‐5D‐VAS score was 71.9±11.1 for those with current MCI/mild AD and 63.7±16.6 for moderate/severe AD.ConclusionFurther improvement is needed in early detection and accurate diagnosis of MCI/AD to lessen the burden to patients, care partners, and society.

To assess the association of tirzepatide use with a 10-year predicted risk of type 2 diabetes (T2D) among Chinese participants with obesity or overweight from the SURMOUNT-CN trial. In this post hoc analysis, the QDiabetes-2018 risk engine was used to calculate the 10-year predicted T2D risk at baseline, week 24 and week 52 among SURMOUNT-CN participants randomized to receive tirzepatide 10 mg, 15 mg or placebo. A mixed model for repeated measures was used to compare mean predicted risk changes from baseline to weeks 24 and 52 between tirzepatide and placebo. Subgroup analyses were conducted by baseline body weight mass index (BMI) status and baseline prediabetes status. Demographic and baseline clinical characteristics were similar among tirzepatide10 mg (n = 59), 15 mg (n = 53) and placebo (n = 57). From baseline to week 52, the least square (LS) mean predicted T2D risk changed from 5.3% to 1.2% for tirzepatide 10 mg, from 4.9% to 1.0% for tirzepatide 15 mg and from 5.8% to 4.5% for placebo. The difference in LS mean risk change from baseline to week 52 was significant between both tirzepatide 10 mg (-3.2%, 95% confidence interval [CI]: -4.2%, -2.2%) and 15 mg (-3.4%, 95% CI: -4.4%, -2.4%) and placebo. Significantly greater predicted risk reductions for tirzepatide than placebo were observed in all subgroups. Tirzepatide was associated with significantly reduced predicted 10-year risk of T2D among SURMOUNT-CN participants with obesity or overweight, irrespective of baseline BMI and prediabetes status.

To describe weight management and perceptions in China. Data were from the Adelphi Real World Obesity Disease Specific Programme™, a cross-sectional survey between April and July 2022 of physicians managing people with obesity or overweight (PwO) and PwO in real-world clinical practice in China. At data collection, eligible PwO were aged ≥18 years, under weight management and/or had a body mass index (BMI) ≥28 kg/m2. In total, 100 physicians and 801 PwO were enrolled. More than two thirds of PwO (70.7%; 531/751) were not diagnosed with obesity until a BMI ≥30 kg/m2. Most PwO (78%; 625/801) were on treatment for at least one obesity-related complication (ORC). Physicians commonly initiated weight loss discussions with PwO who already had an ORC (48.0%; 48/100). According to physicians and PwO, the mean target BMI was set at 25.8 kg/m2 and 24.3 kg/m2, and the mean target percentage weight loss was 19.6% and 23.7%, respectively. Over a median 6.4 months of weight management, the mean percentage weight loss was 4.1%. Few PwO achieved the weight loss target set by their physician (9.9%; 69/695) or themselves (2.0%; 14/696). Most physicians and PwO were unsatisfied with the current weight loss (92.3% [739/801] and 82.0% [650/793], respectively). These findings suggest that earlier intervention may be needed to address obesity as a disease. Most physicians and PwO recognized the importance of normal weight, but few PwO achieved weight loss targets, which may suggest an unmet need for improved weight management.

A design of experiments model has been developed to optimize an electrochemical protocol for the decarboxylative N-alkylation of pyrazole in a spinning cylinder electrode reactor. The electrochemical reaction requires the incorporation of molecular sieves as an additive to ensure the absence of moisture and prevent potential electrode corrosion issues. The spinning cylinder electrode reactor proved to be an idea platform to scale up this transformation, involving a suspension of solid particles, to multigram scales. The reaction model, which showed an excellent fitting with the experimental data, provided insights on the effect of important electrolysis parameters unique to this reactor design, such as the electrode spinning speed, on the reaction conversion and selectivity. Furthermore, the design of experiments also supplied optimal electrolysis parameters for this complex multivariable reaction system, resulting in full conversion of the substrate and excellent selectivity for a 600 mL volume reaction in recirculation flow mode, with 94% isolated yield for the target N-alkylated product.

Tirzepatide is a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist. In the SURPASS-AP-Combo trial, once-weekly tirzepatide was associated with improved glycemic control and weight loss versus insulin glargine and was generally well tolerated in an Asia-Pacific, predominately Chinese, population with type 2 diabetes (T2D). This post hoc subgroup analysis of SURPASS-AP-Combo assessed the potential influence of patient baseline characteristics on the efficacy and safety of tirzepatide. Changes from baseline to week 40 in HbA1c, body weight, fasting serum glucose (FSG), and daily glucose average from self-measured blood glucose profiles were analyzed by potential influential factors including age (< 65, ≥ 65years), sex, baseline HbA1c (≤ 8.5, > 8.5%), body mass index (BMI) (< 25, ≥ 25kg/m2), body weight (< 75, ≥ 75kg), duration of diabetes (< 10, ≥ 10years), and concomitant oral antihyperglycemic medications (metformin, metformin plus sulphonylurea). Gastrointestinal adverse events and hypoglycemia were also evaluated. At week 40, all tirzepatide doses were associated with reduced HbA1c, body weight, FSG, and daily glucose average from baseline in all subgroups. Greater HbA1c reductions were achieved in patients with higher baseline HbA1c across all tirzepatide doses, higher body weight with 10mg and younger age with 15mg tirzepatide. Greater reductions in body weight were observed in patients with higher body weight across all tirzepatide doses, lower baseline HbA1c with 5mg and higher BMI with 5mg tirzepatide. In this post hoc analysis, tirzepatide was associated with reduced blood glucose and body weight in a predominantly Chinese population with T2D across different subgroups, consistent with previous reports for tirzepatide. NCT04093752.

Ixekizumab, an interleukin-17A inhibitor, was efficacious and well tolerated for the treatment of active radiographic axial spondyloarthritis (r-axSpA) in international clinical studies. This phase III study aimed to determine the efficacy and safety of ixekizumab for treating Chinese patients with active r-axSpA. Adults with active r-axSpA naïve to biologic disease-modifying antirheumatic drugs (bDMARDs), or with an inadequate response/intolerance to one tumor necrosis factor inhibitor, were randomized (1:1), double-blind, to receive ixekizumab 80mg every 4 weeks (IXEQ4W; starting dose 160mg), or placebo, for 16weeks. Patients receiving placebo were then switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. The primary endpoint was the proportion of bDMARD-naïve patients achieving an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 16. In total, 147 patients were randomized to receive placebo (n=73) or IXEQ4W (n=74). At week 16, more bDMARD-naive patients achieved ASAS40 in the IXEQ4W group (n=66; 40.9%) than the placebo group (n=64, 7.8%; p<0.001). In the overall study population, ASAS40 was also achieved by more patients in the IXEQ4W group (37.8%) than the placebo group (8.2%; p<0.001) at week 16, with a significant difference observed as early as week 1. There were significant improvements in all key secondary endpoints at week 16 with IXEQ4W versus placebo. Efficacy was sustained at week 52 in patients who continued IXEQ4W and there were also clinical improvements from weeks 16 to 52 in patients switched to IXEQ4W. The safety profile of ixekizumab was consistent with that described previously. Infections and injection-site reactions were the most frequently reported events of special interest. IXEQ4W was associated with rapid and significant improvements in the signs and symptoms of active r-axSpA in Chinese patients at week 16 that were sustained at week 52, with no new safety signals. ClinicalTrials.gov identifier: NCT04285229.

e15557 Background: Fruquintinib, an antiangiogenic tyrosine kinase inhibitor (TKI), has demonstrated its significant survival benefits in metastatic colorectal cancer (mCRC) patients in both China and global phase III trials (FRESCO and FRESCO-2), but data on patients' health-related quality of life (HRQoL) was rare. A previous study on HRQoL of mCRC patients receiving another antiangiogenic TKI or placebo showed a decreased pattern in the mean utility index (UI) score of EuroQol 5-dimension (EQ-5D). This study intended to evaluate the HRQoL of mCRC patients receiving fruquintinib in the real world and describe its real-world treatment outcomes and compliance. Methods: This is a multicenter prospective observational study of patients with mCRC who were treated with fruquintinib monotherapy. Patient demographics, disease characteristics, and treatment history were recorded at baseline (before fruquintinib administration). Dosage record, treatment outcome, and HRQoL, which was measured by EQ-5D-5L scale and then converted to UI score, were recorded in each cycle. The UI score was described in total patients. The changes of it from baseline at key point (first cycle of fruquintinib) and end point (last cycle of fruquintinib) between subgroups, including prior use of VEGF inhibitors, RAS mutation status, etc, were compared by T-test or Wilcoxon rank sum test. Median progression-free survival (mPFS) was calculated using Kaplan-Meier method. The medication compliance rate was summarized according to the dosage record. Results: Data of 70 patients from five centers between May 2021 and November 2022 were evaluated in this study. Fruquintinib was used in second line treatment in 15.7% cases (N = 11), and in third or later line in 84.3% cases (N = 59). The median UI scores of EQ-5D-5L were 0.89, 0.78 and 0.73 at baseline (N = 70), key point of follow-up (N = 62) and end point of follow-up (N = 23), respectively. There was no significant difference between subgroups in median UI score changes from baseline, such as whether VEGF inhibitors were used previously or not (at key point, -0.07 vs. -0.11, p = 0.82, at end point, -0.21 vs. -0.26, p = 0.27), and whether RAS mutation or not (at key point, -0.02 vs. -0.04, p = 0.79, at end point, -0.21 vs. –0.16, p = 0.62). The mPFS of the total population was 4.8 months (N = 69, 95%CI 3.5-6.2), numerically longer than mPFS in FRESCO and FRESCO-2 trials. The mean actual (actual doses per cycle/21 days) and prescribed daily doses were 4.46 mg and 4.65 mg for 21 out of 28 days per patient, respectively. The compliance rate (actual/prescribed) of fruquintinib was 95.91%. Conclusions: As with the previous study, fruquintinib showed a similar gradually declined trend in HRQoL, which may be associated with disease deterioration in heavily pretreated mCRC patients. Fruquintinib has prolonged mPFS with good compliance in clinical practice.