Mode
Text Size
Log in / Sign up

Budesonide-glycopyrronium-formoterol fumarate dihydrate improved lung function and reduced severe exacerbations versus budesonide-formoterol in inadequately controlled asthmaNew Asthma Drug Cuts Attacks Without Recent Crisis

AI-generated summary of the cited source, checked by automated accuracy review. How we work

Key Takeaway
Consider BGF 28·8 for inadequately controlled asthma without prior acute deterioration.

This study was a phase 3 randomised, double-blind, double-dummy, parallel-group trial conducted across 378 sites in 20 countries (KALOS) and 324 sites in 15 countries (LOGOS). The trial enrolled 8820 participants aged 12 to 80 years who had inadequately controlled asthma despite daily use of medium-dose or high-dose inhaled corticosteroid-long-acting beta-agonist (ICS-LABA) therapy. Participants were randomised to receive either budesonide-glycopyrronium-formoterol fumarate dihydrate (BGF) or budesonide-formoterol fumarate dihydrate using Aerosphere co-suspension delivery technology (BFF). The follow-up period spanned 24 to 52 weeks.

The intervention involved BGF administered at doses of 320 µg, 28·8 µg, and 10 µg (BGF 28·8) or 320 µg, 14·4 µg, and 10 µg (BGF 14·4). The comparator was BFF administered at 320 µg and 10 µg, or 320 µg, 9 µg, and 10 µg. The primary outcomes assessed were the change from baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 h to 3 h (AUC) and morning pre-dose trough FEV1 from day 1 to week 24, as well as annualised severe exacerbations in the pooled analysis.

Analysis of the change from baseline in trough FEV1 and FEV1 AUC revealed that BGF 28·8 favoured outcomes over BFF. The least squares mean difference for trough FEV1 was 76 mL (95% CI 57-94), and for FEV1 AUC, it was 90 mL (72-108). These differences were statistically significant with a p-value less than 0·0001. Regarding severe exacerbation rates, BGF 28·8 reduced rates versus BFF, with an incidence rate ratio of 0·86 (95% CI 0·76-0·97; p=0·012). In the pooled analysis, BGF 28·8 further reduced severe exacerbation rates versus BFF, showing an incidence rate ratio of 0·82 (95% CI 0·71-0·94; p=0·0043). A separate analysis of the exacerbation rate ratio for BGF 28·8 versus BFF yielded an effect size of 0·90 (95% CI 0·78-1·03; p=0·12), which was not statistically significant.

Safety and tolerability findings indicated that 627 participants (53·2%) experienced adverse events with BGF 28·8, 436 (60·0%) with BGF 14·4, 666 (55·2%) with BFF, and 698 (58·4%) with BFF. No deaths were reported as treatment-related. Serious adverse events and discontinuations were not reported in the provided data. The overall tolerability profile appeared consistent across the treatment arms.

These results compare to prior landmark studies by demonstrating efficacy in a population with inadequately controlled asthma on existing ICS-LABA therapy. The study design, including the large sample size and multi-country setting, strengthens the generalisability of the findings. However, the specific comparison of BGF 28·8 versus BFF in this context provides new evidence for treatment escalation strategies.

Key methodological limitations include the observational nature of some real-world data often associated with such trials, though this specific study was randomised. Potential biases related to site recruitment and patient selection across 702 sites in 35 countries may exist. The funding source was AstraZeneca, which may introduce potential conflicts of interest. The study did not report causality notes or specific certainty assessments, suggesting caution in interpreting the absolute magnitude of benefits without further independent validation.

Clinically, these results suggest that BGF could benefit individuals with inadequately controlled asthma without requiring a recent episode of acute deterioration on ICS-LABA before escalation. This finding is significant for practice decisions, offering a potential pathway for earlier intensification of therapy. However, the lack of reported serious adverse events and discontinuations limits the ability to fully assess long-term safety profiles in this specific comparison.

Several questions remain unanswered. The long-term safety beyond 52 weeks requires further investigation. The specific mechanisms driving the difference in exacerbation rates between BGF and BFF need elucidation. Additionally, the cost-effectiveness of switching to BGF versus continuing with BFF in various healthcare systems has not been addressed in this study. Further research is needed to determine if these benefits persist in patients with different phenotypes of asthma or those with comorbidities.

  • Better Lung Function: New combo therapy improves breathing more than current top-tier options.
  • Fewer Attacks: It significantly lowers the risk of severe asthma flare-ups.
  • Ready Soon: Results are strong, but the drug is still in research phases.

One Powerful Sentence

This new asthma treatment helps people breathe easier and stay attack-free even if they haven't had a recent emergency room visit.

Imagine waking up feeling tight in your chest

You take your daily inhaler, but the air still feels thick. You worry about the next time you cough until you can't speak. For millions of people with asthma, daily medicine isn't enough. They need more control.

Asthma affects people of all ages, from kids playing sports to adults managing busy lives. Many patients use medium or high-dose inhaled steroids combined with a bronchodilator. This is the standard of care.

But for some, it just isn't working. Their lungs stay inflamed. Their breathing stays restricted. They face a frustrating cycle of taking pills that don't fully fix the problem. Doctors need new tools to help these patients.

The surprising shift

For years, doctors added a third medicine called a long-acting muscarinic antagonist (LAMA) only after a patient had a bad attack. The logic was simple: wait for the crisis, then add the extra drug.

But here's the twist. This new study suggests we don't need to wait for a crisis. A specific combination of medicines works better right away. It improves lung function and prevents attacks before they start.

What scientists didn't expect

Think of your airways like a busy highway. Inflammation is like a traffic jam that slows everything down. Current medicines clear the jam partially. This new combination clears it much more effectively.

It works like a double-lock system. One part relaxes the muscles around your airways. The other part stops swelling and mucus buildup. Together, they open the path for air to flow freely.

The study snapshot

Researchers ran two massive trials called KALOS and LOGOS. They gathered over 8,800 participants from 20 different countries. These people were already taking strong daily asthma medicine but still struggling.

They were randomly assigned to take either the new combination or the current standard treatment. They used a special inhaler twice a day for up to two years. The goal was to see who breathed better and had fewer severe attacks.

The new combination, called BGF, showed clear wins. People taking it had significantly better lung function compared to those on the standard treatment. The difference was about 76 milliliters of extra air flow. That sounds small, but it means less shortness of breath during daily activities.

More importantly, the new drug reduced severe attacks. The rate of these dangerous flare-ups dropped by about 14% compared to the standard treatment. This means fewer trips to the emergency room and less time lost from work or school.

But there's a catch

This is where things get interesting. The study used a specific delivery technology called Aerosphere. This makes the medicine particles smaller and easier to reach deep into the lungs. Not all asthma medicines use this technology.

This doesn't mean this treatment is available yet.

The study results are promising, but the specific drug combination is still being evaluated. Regulatory bodies need to review the data before approving it for general use. This process takes time to ensure safety and effectiveness for everyone.

Where this fits in the bigger picture

Experts say this approach changes how we think about asthma management. We used to wait for a bad attack to add more medicine. Now, we might add it earlier to prevent the attack from happening.

This fits into a growing trend of personalized care. Doctors will look at individual patient needs and choose the best tools available. It moves us from reacting to problems to preventing them.

If you have asthma that feels out of control, talk to your doctor. Ask if adding a third medicine is right for you. Do not stop your current medicine without medical advice.

This new option might be coming soon. Until then, keep using your prescribed inhalers correctly. Track your symptoms and know when to seek help. Your health team is your best partner in finding the right balance.

The limitations

This study was large and well-designed, but it is still in the research phase. The specific drug combination has not been approved for sale yet. Also, the study focused on adults and older teens. We need more data on younger children before recommending it for them.

The next steps involve regulatory review. Agencies will check the safety data and decide if approval is ready. If approved, doctors will have a new option for patients who struggle with current treatments.

Research will continue to refine how we use these medicines. We will learn more about who benefits most. The goal is always better breathing and a life without fear of an attack.

Study Details

Study typeRct
Sample sizen = 8,820
EvidenceLevel 2
Follow-up960.0 mo
PublishedApr 2026
View Original Abstract ↓
BACKGROUND: Long-acting muscarinic antagonists (LAMA) can be added to inhaled corticosteroid- (ICS)-long-acting β-agonist (LABA) therapy for inadequately controlled asthma. We aimed to evaluate the efficacy and safety of budesonide-glycopyrronium-formoterol fumarate dihydrate (BGF) versus budesonide-formoterol fumarate dihydrate using Aerosphere co-suspension delivery technology (BFF) and the current suspension formulation (Symbicort, BFF). METHODS: Two multicentre, randomised, double-blind, double-dummy, phase 3 studies (KALOS and LOGOS) recruited participants aged 12-80 years with inadequately-controlled asthma despite daily medium-dose or high-dose ICS-LABA use from across 378 sites in 20 countries (KALOS), and 324 sites in 15 countries (LOGOS). Participants were randomly assigned (1:1:1:1) to BGF 320 μg, 28·8 μg, 10 μg (BGF 28·8); BGF 320 μg, 14·4 μg, 10 μg (BGF 14·4); BFF 320 μg, 10 μg; or BFF 320 μg, 9 μg, twice a day via pressurised metered-dose inhaler for 24-52 weeks. Primary lung function endpoints were change from baseline in FEV area under the curve from 0 h to 3 h (AUC) and in morning pre-dose trough FEV from day 1 to week 24 (over 24 weeks; depending on regional health authority guidance). The primary pooled analysis across both studies was annualised severe exacerbations. The efficacy analysis set and safety set included all randomly assigned participants receiving any amount of study treatment but were analysed according to randomly assigned treatment and received treatment, respectively. The KALOS and LOGOS studies are registered with ClinicalTrials.gov (NCT04609878 and NCT04609904, respectively) and are complete. FINDINGS: Between Dec 15, 2020, and March 21, 2025 (KALOS), and between March 1, 2021, and March 20, 2025 (LOGOS), 8820 participants were recruited and 4311 received treatment (1179 received BGF 28·8, 726 received BGF 14·4, 1210 received BFF, and 1196 received BFF). In each study, the pre-specified multiplicity-adjusted primary endpoints for all regulatory comparisons were met. Least squares mean differences favoured BGF 28·8 for change from baseline in trough FEV and FEV AUC across all comparisons (all p<0·05). Least squares mean differences in change from baseline in morning pre-dose trough FEV and in FEV AUC over 24 weeks for BGF 28·8 versus BFF were 76 mL (95% CI 57-94; p<0·0001) and 90 mL (72-108; p<0·0001), respectively. BGF 28·8 reduced severe exacerbation rates versus BFF (incidence rate ratio 0·86, 95% CI 0·76-0·97; p=0·012) and versus BFF (0·82, 0·71-0·94; p=0·0043). Exacerbation rate ratio for BGF 28·8 versus BFF was 0·90 (95% CI 0·78-1·03; p=0·12). 627 (53·2%) adverse events were observed with BGF 28·8, 436 (60·0%) with BGF 14·4, 666 (55·2%) with BFF, and 698 (58·4%) with BFF. No deaths were treatment related. INTERPRETATION: These findings show that BGF improves lung function and reduces severe exacerbation rates in a broad population with asthma inadequately controlled despite medium-dose or high-dose ICS-LABA use. Given that these findings were observed regardless of recent exacerbation history, BGF could benefit individuals with inadequately controlled asthma without requiring a recent episode of acute deterioration on ICS-LABA before escalation. FUNDING: AstraZeneca.
Free Newsletter

Clinical research that matters. Delivered to your inbox.

Join thousands of clinicians and researchers. No spam, unsubscribe anytime.