Roche/Ionis ASO Therapy Meets Primary Endpoint in Phase 3 IgA Nephropathy Study; AstraZeneca Triple Inhaler Wins EU Approval for Asthma

Roche and Ionis's antisense oligonucleotide therapy for IgA nephropathy met its primary endpoint in a Phase 3 study, while AstraZeneca's triple inhaler therapy won European approval for asthma treatment, and Vertex's APOL1 inhibitor showed promising Phase 2b results in kidney disease.

Roche and Ionis Pharmaceuticals announced positive interim results from the Phase 3 IMAgINATION study of sefaxersen, an antisense oligonucleotide therapy targeting mRNA, in patients with primary IgA nephropathy.

The study achieved its primary endpoint, demonstrating a statistically significant and clinically meaningful reduction in 24-hour urine protein/creatinine ratio compared with placebo at Week 37. The companies plan to present detailed data at an upcoming medical conference and share the interim analysis with regulatory authorities.

The IMAgINATION trial is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study that enrolled 459 adult patients with primary IgA nephropathy at high risk of disease progression. Patients were randomized 1:1 to receive subcutaneous injections of sefaxersen or placebo for 105 weeks. The primary endpoint was the change in urine protein/creatinine ratio from baseline at Week 37, with the study continuing in blinded fashion through Week 105 to assess changes in kidney function using estimated glomerular filtration rate.

The prespecified interim analysis showed that sefaxersen achieved a statistically significant and clinically meaningful reduction in proteinuria at Week 37 compared with placebo. Safety and tolerability characteristics were consistent with previously published data, with no new safety signals identified.

Sefaxersen is a liver-targeted investigational antisense oligonucleotide that targets the mRNA encoding complement factor B, reducing its production in the liver and thereby providing sustained inhibition of the alternative complement pathway. Abnormal activation of the alternative complement pathway is considered one of the important drivers of kidney injury associated with IgA nephropathy. The drug is designed for once-monthly subcutaneous injection and can be self-administered by patients.

Sefaxersen was originally discovered and developed by Ionis, with Roche having licensed the drug for complement-mediated diseases. IgA nephropathy is a chronic, progressive autoimmune kidney disease, with long-term disease progression potentially leading to sustained decline in kidney function.

AstraZeneca announced that the European Commission has approved Trixeo Aerosphere, a fixed-dose triple inhaler therapy containing budesonide, glycopyrronium, and formoterol fumarate dihydrate, as maintenance treatment for asthma patients aged 12 and older whose disease remains inadequately controlled on medium-dose inhaled corticosteroids combined with long-acting beta-2 agonists.

According to the press release, Trixeo is the first triple inhaler therapy approved in the European Union for patients aged 12 and older without restriction on prior acute exacerbation history.

The approval was primarily based on positive results from the Phase 3 KALOS and LOGOS studies. Both studies employed a replicate validation design and were randomized, double-blind, double-dummy, parallel-group, multicenter Phase 3 trials that collectively randomized approximately 4,300 asthma patients to compare the efficacy and safety of Trixeo versus inhaled corticosteroid/long-acting beta-2 agonist dual therapy. The primary lung function endpoint for individual studies was the change from baseline in pre-morning dose trough forced expiratory volume in one second over 24 weeks; the primary endpoint for pooled analysis of both studies was the annualized rate of severe asthma exacerbations compared with inhaled corticosteroid/long-acting beta-2 agonist dual treatment.

Study results showed that compared with active control, Trixeo significantly improved patient lung function. In the pooled analysis of KALOS and LOGOS, Trixeo also significantly reduced the annualized rate of severe asthma exacerbations, an analysis that covered a broad patient population including those who had not experienced an asthma exacerbation in the prior year. No new safety or tolerability signals were identified in either study. Related results were published in The Lancet Respiratory Medicine in February 2026.

Trixeo integrates three classes of drugs—inhaled corticosteroids, long-acting beta-2 agonists, and long-acting muscarinic antagonists—into a single inhaler, containing three active ingredients: budesonide, formoterol fumarate dihydrate, and glycopyrronium.

The product is marketed under the brand name Breztri Aerosphere for asthma treatment in the United States, Japan, and other markets, and has also been approved for adult chronic obstructive pulmonary disease in more than 90 countries and regions globally.

Vertex Pharmaceuticals announced positive results from the Phase 2b AMPLIFIED study of inaxaplin, an oral APOL1 inhibitor, in patients with APOL1-mediated kidney disease.

The study evaluated inaxaplin in patients with APOL1-mediated kidney disease with moderate proteinuria, as well as in patients with APOL1-mediated kidney disease complicated by type 2 diabetes. Concurrently, Vertex announced that enrollment has been completed for the pivotal Phase 2/3 AMPLITUDE study, with interim analysis results expected in early 2027.

AMPLIFIED is a Phase 2b study in which 41 patients received treatment. Cohort 1 enrolled 23 patients with APOL1-mediated kidney disease and moderate proteinuria, while Cohort 2 enrolled 18 patients with both type 2 diabetes and proteinuria in the setting of APOL1-mediated kidney disease. Both groups received 45 mg of inaxaplin once daily for 13 weeks in addition to optimized standard of care. The primary endpoint was the mean percentage change in urine albumin/creatinine ratio from baseline at Week 13 for each cohort.

Results showed that in patients with APOL1-mediated kidney disease and moderate proteinuria, the mean reduction in urine albumin/creatinine ratio from baseline at Week 13 was 42.7%; in patients with APOL1-mediated kidney disease complicated by type 2 diabetes, the mean reduction from baseline was 17.3%. In both cohorts, inaxaplin was generally well-tolerated with good safety and tolerability profiles. No treatment-related serious adverse events were reported, and all adverse events were mild or moderate in severity.

Inaxaplin is an investigational oral small-molecule APOL1 inhibitor designed to target the mechanism of kidney disease caused by APOL1 gene variants. Vertex is currently evaluating the efficacy and safety of inaxaplin in patients with APOL1-mediated kidney disease in the pivotal AMPLITUDE study. The study has completed enrollment, with interim analysis results expected in early 2027; the company indicated that if results are positive, the data could potentially support seeking accelerated approval in the United States.