Novo Nordisk’s STEP Young Phase 3 Results Highlight Semaglutide’s Potential in Pediatric Obesity; Clover Reports Positive Phase 2 Clinical Findings for RSV + hMPV ± PIV3 Vaccine Candidates; Novartis Reveals Topline Results From Phase III Lp(a)HORIZON Trial of Pelacarsen; US Approves Etcamah Plus CDK4/6 Inhibitor for 1st-Line Advanced HR-Positive Breast Cancer; ZANVASTRO Wins FDA Approval as a First-of-Its-Kind Disease-Modifying Treatment for Alexander Disease

Novo Nordisk’s STEP Young Phase 3 Study Shows Semaglutide Reduced Obesity Classification in 40.4% of Children

Novo Nordisk announced the initial results from the STEP Young Phase 3 trial, which evaluated once-weekly semaglutide in combination with lifestyle modifications, including a reduced-calorie diet and increased physical activity, in children aged 6 to under 12 years living with obesity. The study addresses a growing health concern in this age group, where treatment options supported by clinical evidence and regulatory approval remain limited when lifestyle interventions alone are insufficient.

At the start of the study, more than 85% of participants had class II or class III severe obesity, corresponding to adult BMI thresholds of 35 and 40, respectively. The trial achieved its primary endpoint, demonstrating a significantly greater reduction in BMI at week 68 among children receiving semaglutide compared with those receiving placebo. By week 68, 40.4% of children treated with semaglutide were no longer classified as having obesity, compared with none in the placebo group. In other words, approximately two in five children receiving semaglutide reduced their BMI to a classification of normal weight or overweight, while no children in the placebo group reached this outcome. Both treatment groups continued lifestyle modifications throughout the study.

According to Ania M. Jastreboff, MD, PhD, Professor of Medicine and Pediatrics at Yale and Director of the Yale Obesity Research Center, childhood obesity is particularly concerning because of its immediate and long-term health consequences. She noted that most participants in STEP Young had severe class II or III obesity at baseline, while treatment with semaglutide enabled approximately 40% of children to achieve a BMI percentile below the obesity threshold within about one year of treatment.

Childhood obesity is associated with multiple physical and psychosocial consequences, including cardiovascular risk factors, depression, eating disorders, and bullying. Research has also indicated a substantial impact on quality of life. Without effective intervention, obesity during childhood frequently persists into adulthood, increasing the likelihood of obesity-related complications occurring earlier and with greater severity and potentially contributing to reduced life expectancy. An estimated 177 million children aged 5 to 19 years were living with obesity in 2025, with this number projected to increase to approximately 228 million by 2040.

The overall safety and tolerability profile of semaglutide in the STEP Young trial was consistent with observations from previous Novo Nordisk pediatric and adult studies evaluating semaglutide and liraglutide. No new safety concerns were identified, and the trial did not reveal any safety concerns related to growth or pubertal development.

Clover Announces Encouraging Phase 2 Data for Multivalent RSV + hMPV ± PIV3 Vaccine Candidates

Clover Biopharmaceuticals, Ltd. announced positive preliminary results from an ongoing Phase 2 clinical trial in older adults in Australia evaluating two protein-based combination vaccine candidates, SCB-1022 (RSV + hMPV) and SCB-1033 (RSV + hMPV + PIV3). Both candidates are based on prefusion-stabilized F (PreF)-Trimer subunit vaccine antigens developed using Clover’s validated Trimer-Tag vaccine technology platform.

According to Joshua Liang, Chief Executive Officer and Board Director of Clover, the positive Phase 2 findings support the potential first-in-class and best-in-class profiles of the company’s RSV+hMPV±PIV3 combination vaccine candidates. The candidates may also offer a differentiated approach to revaccinating individuals who have previously received approved RSV vaccines, with the potential to restore and broaden protection. The results are expected to reduce risks associated with future late-stage development and further validate Clover’s Trimer-Tag platform for developing multivalent, protein-based respiratory vaccines. The platform could potentially support the development of vaccines aimed at addressing public health needs and chronic diseases associated with respiratory viral infections.

The ongoing Phase 2 study is a randomized, observer-blinded, multicenter trial that enrolled 420 adults aged 60–85 years in Australia. Participants were randomized to receive either SCB-1022, SCB-1033, or placebo.

Novartis Reports Topline Phase III Lp(a)HORIZON Results for Pelacarsen in Patients With Elevated Lp(a) and CVD

Novartis announced that its Phase III Lp(a)HORIZON trial of pelacarsen did not achieve its primary endpoint of reducing the risk of major cardiovascular events compared with placebo. The composite endpoint included cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization requiring hospitalization. Although pelacarsen successfully lowered lipoprotein(a) [Lp(a)] levels in the study population, participants were also receiving guideline-directed therapies, including lipid-lowering and antihypertensive treatments.

The results provide important evidence for understanding the relationship between Lp(a) reduction and cardiovascular outcomes. Elevated Lp(a) is an inherited risk factor for cardiovascular disease and affects approximately one in five people globally. Despite its prevalence, there are currently no approved therapies specifically targeting elevated Lp(a).

According to Shreeram Aradhye, President, Development and Chief Medical Officer at Novartis, Lp(a)HORIZON was designed to determine whether lowering Lp(a) could reduce residual cardiovascular risk beyond optimized guideline-directed care in patients whose other major cardiovascular risk factors were already being managed. While pelacarsen demonstrated reductions in Lp(a) levels, these changes did not translate into a reduction in cardiovascular risk across the overall study population. Novartis noted that, although the findings were not as anticipated, they contribute to the scientific understanding of Lp(a) lowering and its potential impact on cardiovascular outcomes.

Novartis also expressed its appreciation to the more than 8,000 participants and investigators involved in the trial and reaffirmed its commitment to advancing cardiovascular innovation. Detailed findings from the Lp(a)HORIZON trial are expected to be presented at an upcoming medical congress.

FDA Clears Etcamah in Combination With CDK4/6 Inhibitors for 1st-Line Advanced HR-Positive Breast Cancer

AstraZeneca’s Etcamah (camizestrant), when used in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor such as abemaciclib, palbociclib, or ribociclib, has received approval in the US for the treatment of adults with hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer following the detection of an ESR1 mutation during treatment with an aromatase inhibitor (AI) and a CDK4/6 inhibitor. The indication is based on the use of a US Food and Drug Administration (FDA)-approved test.

The accelerated approval was supported by findings from the pivotal Phase III SERENA-6 trial, which were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published concurrently in The New England Journal of Medicine.

According to Kevin Kalinsky, MD, MS, FASCO, Division Director of Medical Oncology at Winship Cancer Institute of Emory University and an investigator in the trial, the combination offers a new treatment option for approximately one-third of patients with advanced breast cancer whose tumors develop ESR1 mutations before clinical or radiographic disease progression. The approval allows physicians to identify endocrine resistance earlier and modify treatment before disease progression, potentially helping to prevent deterioration in outcomes and quality of life.

Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, noted that the approval represents the company’s tenth FDA approval across its portfolio in 2026 and its fourth in breast cancer. He highlighted Etcamah’s combination approach as part of AstraZeneca’s efforts to transform breast cancer treatment through the use of circulating tumor DNA (ctDNA), describing it as the first and only therapy of its type approved for use in the first-line setting.

In a planned interim analysis of SERENA-6, treatment with Etcamah plus a CDK4/6 inhibitor reduced the risk of disease progression or death by 56% compared with standard treatment consisting of an AI, either anastrozole or letrozole, combined with a CDK4/6 inhibitor. The analysis reported a hazard ratio (HR) of 0.44 (95% confidence interval [CI]: 0.31–0.60; p<0.00001), with median progression-free survival (PFS) of 16.0 months for the Etcamah combination versus 9.2 months for standard care.

Although data for the key secondary endpoints of time to second disease progression (PFS2) and overall survival (OS) were immature at the interim analysis, a subsequent pre-planned analysis demonstrated a statistically significant and clinically meaningful PFS2 benefit. Median PFS2 was 25.7 months with the Etcamah combination compared with 19.1 months for standard treatment, corresponding to an HR of 0.63 (95% CI: 0.46–0.86; p=0.00373). OS also continued to favor the Etcamah combination, with an HR of 0.87 (95% CI: 0.57–1.30), although the data remain immature. The SERENA-6 trial will continue to evaluate OS as a key secondary endpoint.

The safety profile of Etcamah combined with palbociclib, ribociclib, or abemaciclib was consistent with the established safety profiles of the individual medicines. No new safety signals were identified, while treatment discontinuation rates remained very low and comparable between the two treatment groups.

Alongside the approval, the FDA also authorized a companion diagnostic designed to identify emerging ESR1 resistance mutations in the ctDNA of patients with HR-positive, HER2-negative advanced or metastatic breast cancer. SERENA-6 represents the first global, double-blind, registrational Phase III trial to use a ctDNA-guided strategy to detect emerging endocrine resistance and enable treatment modification before radiographic or clinical disease progression.

Under the trial’s innovative design, patients underwent blood-based ctDNA testing at the time of routine tumor imaging, conducted every two to three months. Patients who developed an ESR1 mutation without evidence of disease progression were identified as having early endocrine resistance and switched from their existing AI to Etcamah while continuing treatment with the same CDK4/6 inhibitor.

Etcamah has also secured approvals in more than 30 countries worldwide, including the European Union, Japan, Canada, the UK, and several other markets, based on data from the Phase III SERENA-6 trial.

FDA Approves ZANVASTRO for Pediatric and Adult Alexander Disease in Landmark Treatment Milestone

Ionis Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved ZANVASTRO (zilganersen) for the treatment of Alexander disease (AxD) in both pediatric and adult patients. ZANVASTRO is the first and only disease-modifying therapy approved for AxD, an ultra-rare, progressive, and potentially fatal neurological disorder that can impair motor, cognitive, autonomic, and gastrointestinal functions. Prior to this approval, treatment options for AxD were primarily focused on symptom management.

ZANVASTRO is an RNA-targeted therapy designed to address the underlying mechanism of AxD by reducing the production of glial fibrillary acidic protein (GFAP). The treatment is administered as a 50 mg intrathecal injection once every three months.

According to Ionis, the FDA approval represents a significant advancement for individuals with AxD and their families, who previously had no disease-modifying treatment options. The approval also represents Ionis’ first independent commercial launch from its neurology pipeline and highlights the potential of its RNA-targeted technology to address serious neurological disorders with limited therapeutic options. The company acknowledged the contributions of clinical trial participants and their families, investigators, regulators, and patient advocates to the development and approval of ZANVASTRO.

Alexander disease affects an estimated 1 in 1 million to 3 million people worldwide. The disease can emerge at any stage from infancy to adulthood, with clinical manifestations varying according to the age of onset. As the disease progresses, patients may develop worsening motor and cognitive impairment, loss of independence, and difficulties controlling the muscles required for swallowing, airway protection, and purposeful movement.

AxD is associated with mutations in the GFAP gene that result in excessive production and toxic accumulation of GFAP within astrocytes. Progressive astrocyte dysfunction can subsequently damage neurons and myelin, contributing to the neurological symptoms associated with the disease.

The FDA approval was supported by positive findings from the pivotal ZANVASTRO clinical study. Among patients aged 5 years and older, ZANVASTRO 50 mg achieved the primary endpoint by demonstrating statistically significant and clinically meaningful stabilization of gait speed, measured using the 10-Meter Walk Test (10MWT), compared with the control group at Week 61. The least-squares mean difference was 33.3% (p=0.041). In patients aged 2 to 4 years, ZANVASTRO also demonstrated improvements in gross motor function, as assessed using the Gross Motor Function Measure-88 (GMFM-88), at Week 61 compared with control. Results from secondary and exploratory endpoints, including patient-, caregiver-, and clinician-reported assessments, consistently favored ZANVASTRO.

ZANVASTRO demonstrated a favorable safety and tolerability profile in the pivotal study, with most adverse events reported as mild or moderate in severity. Serious treatment-emergent adverse events occurred less frequently among patients receiving ZANVASTRO than among those in the control group.

In conjunction with the approval, the FDA awarded Ionis a Rare Pediatric Disease Priority Review Voucher (PRV). The program is intended to encourage the development of therapies for serious or life-threatening rare pediatric diseases and provides an opportunity to potentially expedite the FDA review process for a future regulatory application.