Latest news with #phase3
Medscape
2 days ago
- Health
- Medscape
JAK1 Inhibitor Shows Promise for Ankylosing Spondylitis
TOPLINE: Ivarmacitinib, a highly selective Janus kinase 1 (JAK1) inhibitor, tamed ankylosing spondylitis with sustained efficacy through 24 weeks in a phase 2/3 trial. METHODOLOGY: A phase 2/3 trial in China evaluated the efficacy and safety of ivarmacitinib in 504 adults with active ankylosing spondylitis who did not benefit from nonsteroidal anti-inflammatory drugs (NSAIDs). In phase 2, patients were randomly assigned to receive ivarmacitinib (2 mg, 4 mg, or 8 mg) or placebo once daily for 12 weeks; 4 mg was selected as the recommended dose based on an interim analysis. In phase 3, 373 patients (mean age, 33.8 years; 79.6% men) were randomly assigned to receive 4 mg ivarmacitinib (n = 187) or placebo (n = 186) once daily for 12 weeks, after which all patients got ivarmacitinib for 12 weeks. The primary endpoint in both phases was the proportion of patients achieving an Assessment of Spondyloarthritis International Society (ASAS) 20 response at week 12. TAKEAWAY: At week 12, 48.7% of patients who received 4 mg ivarmacitinib achieved an ASAS20 response compared with 29% of those who received placebo (P = .0001). More patients on 4 mg ivarmacitinib vs placebo achieved an ASAS40 response (32.1% vs 18.3%; P = .0011) and an ASAS5/6 response (42.8% vs 15.6%; P < .0001) at week 12, with efficacy sustained at week 24. After 12 weeks of treatment, patients receiving 4 mg ivarmacitinib had greater improvements in disease symptoms, physical function, spinal mobility, and quality of life. During the first 12-week period, treatment-emergent adverse events occurred in 79.7% of patients in the ivarmacitinib group and 65.6% in the placebo group but caused few treatment discontinuations. IN PRACTICE: 'Ivarmacitinib 4 mg once daily provided rapid, sustained, and clinically meaningful improvements in disease activity, signs and symptoms, function, and MRI-detected inflammation in patients with active AS [ankylosing spondylitis] who had an inadequate response to NSAIDs, with a manageable safety profile,' the authors wrote. SOURCE: This study was led by Xu Liu, MD, and Liling Xu, MD, of Peking University People's Hospital in Beijing, China. It was published online on June 12, 2025, in Arthritis & Rheumatology. LIMITATIONS: The 24-week efficacy of ivarmacitinib may not reflect long-term outcomes. The absence of an active comparator limited the comparison of ivarmacitinib with other disease-modifying antirheumatic drugs used for active ankylosing spondylitis. These findings in Chinese patients with radiographic axial spondyloarthritis may not be generalizable to other populations. DISCLOSURES: Jiangsu Hengrui Pharmaceuticals Co. Ltd. sponsored and designed the trial. Two authors reported being employees of the sponsor company while the study was conducted. This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Medscape
17-06-2025
- Health
- Medscape
Is This Drug a Statin Alternative?
Monotherapy with inclisiran — an injectable small interfering RNA that targets hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) — reduced levels of low-density lipoprotein (LDL) cholesterol more effectively than placebo or ezetimibe in patients at a low-to-borderline risk for atherosclerotic cardiovascular disease who were not receiving any lipid-lowering therapy, with a favorable safety profile. METHODOLOGY: Previous studies have shown the efficacy of inclisiran in lowering the level of LDL cholesterol when used in combination with statins in patients with a high risk for atherosclerosis; however, its efficacy as a monotherapy without statins remains uncertain. Researchers conducted a 6-month multinational, randomized, phase 3 study to compare the efficacy and safety of inclisiran with those of placebo or ezetimibe in reducing levels of LDL cholesterol. They included 350 participants (mean age, 46.1 years; 62.6% women) with no history of atherosclerotic cardiovascular disease , diabetes, or familial hypercholesterolemia and a fasting LDL cholesterol level of 100-190 mg/dL. Participants were randomly assigned to receive subcutaneous inclisiran (n = 174), oral ezetimibe (n = 89), or matching placebo (n = 87), with inclisiran administered on days 1 and 90. The primary endpoint was the percentage change in the level of LDL cholesterol from baseline to day 150; several secondary endpoints, including the absolute change in LDL and safety, were assessed. TAKEAWAY: By day 150, participants who received inclisiran showed a 47.9% greater reduction in the level of LDL cholesterol than those who received placebo and a 35.4% greater reduction than those who received ezetimibe ( P < .0001 for both). < .0001 for both). The absolute reduction in the level of LDL cholesterol and the percentage reduction in PCSK9 levels were also greater in participants who received inclisiran than in those who received placebo or ezetimibe ( P < .0001 for all). < .0001 for all). In the group who received inclisiran, levels of lipoprotein(a) decreased by 25.2% compared with placebo ( P = .001) and by 24.3% compared with ezetimibe ( P = .0002) by day 150. = .001) and by 24.3% compared with ezetimibe ( = .0002) by day 150. Similar rates of treatment-emergent adverse events were noted across the three groups, with no new safety concerns. IN PRACTICE: 'There is a significant unmet clinical need for therapies that address both statin intolerance and adherence in primary prevention,' the researchers noted. 'Inclisiran is potentially uniquely positioned to meet these challenges owing to its first-in-class mechanism of action, favorable safety profile, and infrequent twice-yearly dosing,' they added. SOURCE: This study was led by Pam R. Taub, MD, of the University of California in San Diego. It was published online on June 9, 2025, in Journal of the American College of Cardiology . LIMITATIONS: A short follow-up duration and limited sample size prevented the researchers from evaluating the cardiovascular outcomes of lowering the level of LDL cholesterol with inclisiran. The analysis lacked direct comparison with statins, anti-PCSK9 monoclonal antibodies, or bempedoic acid. The response of LDL with ezetimibe was lower than that observed in other studies. DISCLOSURES: This study received funding from Novartis Pharma. Two authors reported receiving compensation for serving as principal investigators of this trial, and another author reported serving as a consultant for multiple pharmaceutical companies including the funding agency. Several other authors reported serving as employees of the US or Switzerland wings of the funding agency or being principal investigator, consultants, and/or holding shares in the same.
Medscape
02-06-2025
- Business
- Medscape
Recombinant Flu Shots Extend Protection to Children
The quadrivalent recombinant influenza vaccine (RIV4) demonstrated non-inferior immune responses in children and adolescents aged 9-17 years compared with adults aged 18-49 years, with the safety profile comparable between both age groups, providing a suitable alternative to egg-based formulations for children. METHODOLOGY: Researchers conducted a phase 3, non-randomised, immunobridging study during the 2022-2023 northern hemisphere influenza season to evaluate whether immune responses to RIV4 in children (aged 9-17 years) were non-inferior to those in adults (aged 18-49 years). They enrolled 648 children and adolescents (mean age, 13 years; 52% boys) and 660 adults (mean age, 34.3 years; 40% men). All participants received a single intramuscular dose of RIV4 (45 μg haemagglutinin of each of A/H1N1, A/H3N2, B/Victoria, and B/Yamagata strains) and were monitored for 6 months on days 9, 29, and 181. The endpoint was measured using haemagglutination inhibition (HAI) titre ratios and the difference in seroconversion rates at day 29 post-vaccination. Non-inferiority was established if the lower limit of the 95% CI exceeded 0.667 for geometric mean titre ratios and −10% or above for seroconversion, for each of the four strains. TAKEAWAY: At day 29, the ratio of geometric mean HAI titres between children and adolescents and adult groups was well above the prespecified non-inferiority margin for A/H1N1 (2.0; 95% CI, 1.7-2.3), H3N2 (3.3; 95% CI, 2.8-3.9), B/Victoria (1.6; 95% CI, 1.4-1.8), and B/Yamagata (1.2; 95% CI, 1.1-1.4) strains. Similarly, the difference in seroconversion rates between the two groups was also above the prespecified non-inferiority margin for all the four strains. The safety profile of RIV4 was comparable between the two groups; however, solicited reactions within 7 days post-vaccination were less common in children and adolescents than in adults. None of the serious and medically attended adverse events were related to the vaccine, and no deaths or adverse events of special interest were reported in either group. IN PRACTICE: "Having multiple influenza vaccine options is crucial to successfully combating influenza, and these options need to be available for children. Prioritising children in influenza vaccine studies is an important step in combating the global burden of influenza," the authors of a commentary wrote. SOURCE: This study was led by Pedro M. Folegatti, DPhil, Sanofi, Marcy-l'Étoile, France. It was published online on May 21, 2025, in The Lancet Infectious Diseases . LIMITATIONS: This study did not investigate immune responses in children younger than 9 years. The evaluation was limited to just one influenza season, and no clinical testing for influenza disease or infection was conducted, potentially accounting for some of the increased antibody responses observed. DISCLOSURES: This study was funded by Sanofi. Seven authors reported being employees of and may have held shares in Sanofi. Two other authors reported having financial ties with other pharmaceutical companies.
Medscape
28-05-2025
- General
- Medscape
Eptinezumab for Episodic Cluster Headache Prevention
Compared with placebo, eptinezumab failed to significantly reduce the number of episodic cluster headache (ECH) attacks but showed higher responder rates and improved quality-of-life measures. METHODOLOGY: Eptinezumab, an anti–calcitonin gene-related peptide monoclonal antibody, was evaluated for the treatment of ECH. This phase 3, double-blind, placebo-controlled trial (ALLEVIATE) was conducted across 64 sites in 18 countries from December 2020 to October 2023 and screened 628 adults with ECH. A total of 231 adults (aged 18-75 years; mean age, 44 years; 78% men) meeting the criteria (a history of ECH for 1 or more years and seven or more CH attacks during screening) were randomly assigned to receive either eptinezumab 400 mg (n = 113) or placebo (n = 118) via intravenous infusion. After the 4-week placebo-controlled phase, participants who received placebo transitioned to delayed-start active treatment for an additional 4 weeks, followed by 12 weeks of observation and an 8-week safety follow-up. The primary outcome was the change from baseline in the number of weekly attacks (weeks 1-2), assessed via a daily electronic diary; secondary outcomes included responder rates of 50% or greater/75% or greater; pain severity; change in disease status, assessed using the Patient Global Impression of Change (PGIC); quality of life, assessed using the Sleep Impact Scale; participant well-being, assessed using the EQ-5D-5L; and self-rated productivity, assessed using the Work Productivity and Activity Impairment. TAKEAWAY: No significant reduction in the number of weekly attacks were observed with eptinezumab vs placebo during weeks 1 and 2 (least-square mean difference, 0.7; P = .50). = .50). A higher proportion of eptinezumab-treated participants achieved 50% or greater response than placebo-treated participants over week 2 (50.9% vs 37.3%; odds ratio [OR], 1.77; P = .04), week 3 (62.5% vs 43.8%; OR, 2.26; P = .004), and week 4 (66.7% vs 50.5%; OR, 2.14; P = .009). = .04), week 3 (62.5% vs 43.8%; OR, 2.26; = .004), and week 4 (66.7% vs 50.5%; OR, 2.14; = .009). Compared with placebo, eptinezumab demonstrated improvements for 75% or greater responder rates by week 4 (35.5% vs 52.0%; OR, 1.98; P = .02). = .02). Numerically greater improvements were observed with eptinezumab than with placebo in terms of PGIC scores, EQ-5D-5L visual analog scale scores (mean difference, 7.8 points; P = .02), and sleep/activity metrics. = .02), and sleep/activity metrics. Treatment-emergent adverse events were similar between eptinezumab and placebo (25.0% and 26.5%, respectively), confirming tolerability. IN PRACTICE: "Among adults with episodic cluster headache, eptinezumab did not significantly reduce the number of attacks vs placebo, although it was associated with numerically higher responder rates and improvements in average daily pain and patient-reported outcomes. Eptinezumab was generally well tolerated," the authors of the study wrote. SOURCE: This study was led by Rigmor H. Jensen, Danish Headache Center, Department of Neurology, Rigshospitalet-Glostrup, University of Copenhagen, Copenhagen, Denmark. It was published online on May 19 in JAMA Neurology . LIMITATIONS: T he study's generalisability may be limited due to the predominantly male (78%) and European population. Early termination due to futility reduced the sample size, although the cohort remained sufficient for the primary analysis. The 4-week placebo-controlled period was too brief to assess the long-term efficacy, unlike the 12-week regimens used for migraine prevention. DISCLOSURES: This trial was sponsored and funded by H. Lundbeck A/S, including medical writing support. Jensen reported receiving grants from Københavns Universitet, Lundbeck Pharma, Novo Nordisk, and Lundbeck Foundation paid to the institution during the conduct of the study. Additional disclosures are noted in the original article.
Medscape
22-05-2025
- Health
- Medscape
Secukinumab Cuts Chronic Pain in Hidradenitis Suppurativa
Compared with placebo, secukinumab demonstrated superior pain reduction in moderate to severe hidradenitis suppurativa in two phase 3 trials. Improvements in pain were sustained through week 52 and were associated with better quality of life outcomes. METHODOLOGY: Researchers analysed 1084 patients with moderate to severe hidradenitis suppurativa from two phase 3 trials (SUNSHINE and SUNRISE) and randomly assigned them to receive secukinumab 300 mg subcutaneously every 2 weeks (SECQ2W) or every 4 weeks (SECQ4W) or placebo until week 16. At week 16, patients randomly assigned to receive placebo switched to receive SECQ2W (placebo-SECQ2W) or SECQ4W (placebo-SECQ4W) until week 52, whereas those originally randomly assigned to receive SECQ2W or SECQ4W continued this treatment until week 52. Pain was assessed using the Patient's Global Assessment of Skin Pain on a continuous numeric rating scale (NRS) through week 52; the severity of pain was categorised into quartiles on the basis of baseline scores (NRS ≤ 3.3, NRS > 3.3 to ≤ 5.4, NRS > 5.4 to ≤ 7.2, and NRS > 7.2). This post hoc analysis of pooled data from the two trials evaluated the effect of secukinumab on multiple aspects of pain and in different subgroups of patients with hidradenitis suppurativa. TAKEAWAY: At week 16, a greater mean absolute change from baseline in skin pain was observed with secukinumab treatment (SECQ2W: mean difference, −1.35; SECQ4W: mean difference, −1.05) than with placebo (mean difference, −0.47). Reductions in skin pain in the secukinumab groups at week 16 were sustained, with a trend for improvement through week 52. Similar improvements were observed in placebo-SECQ2W and placebo-SECQ4W groups. Among patients with severe baseline pain (NRS > 7.2), 20.0% in the SECQ2W group and 12.7% in the SECQ4W group achieved significant pain reduction (NRS ≤ 3.3) at week 16. Patients achieving lower pain scores (NRS ≤ 3.3) experienced better quality of life outcomes. In the secukinumab groups, the proportion of patients requiring pain medication decreased at weeks 16 and 52 compared with baseline. IN PRACTICE: "This post hoc analysis of the SUNSHINE and SUNRISE phase 3 trials highlights the benefits of secukinumab in reducing skin pain in patients with moderate to severe HS [hidradenitis suppurativa], seen within a few weeks of treatment initiation, and sustained, with a trend for improvement, through week 52," the authors wrote. "Importantly, improvements in disease-related pain were associated with improvements in QoL [quality of life] of patients, as well as a decrease in the proportion of patients taking pain medication," they added. SOURCE: This study was led by John R. Ingram, Department of Dermatology & Academic Wound Healing, Division of Infection and Immunity, Cardiff University, Cardiff, Wales. It was published online on May 15, 2025, in Dermatology and Therapy . LIMITATIONS: Changes in skin pain observed may have been influenced by the use of concomitant medications and cannot be fully attributed to the study treatment alone. The cutoffs used for assessing skin pain categories were based on baseline NRS quartiles due to the absence of validated cutoffs for the hidradenitis suppurativa population. Additionally, the study population predominantly consisted of self-reported White participants, with a relatively low proportion of Black patients potentially limiting the generalisability of the findings to the broader global population. DISCLOSURES: This study was funded by Novartis Pharma AG, Basel, Switzerland. One author declared being an employee and stockholder at Novartis Ireland Limited, Dublin, Ireland. Four authors declared being employees of Novartis Pharma AG, Basel, Switzerland. One author declared being an employee of Novartis Pharmaceuticals, East Hanover, New Jersey, United States, at the time of the study. Several authors reported receiving consulting fees and having other ties with various sources.
