[Dr Miller]:
Greetings and welcome to
“Redefining COPD Management in Patients With an Eosinophilic Phenotype”
[Dr Miller]:
I’m Dr Andrew Miller, a Medical Director of Pulmonary & Critical Care Medicine at Medical City Arlington in Arlington, Texas, and Assistant Professor of Internal Medicine at the TCU School of Medicine.
[Dr Smith]:
And I am Dr Alexis Smith, a Pulmonologist specializing in Pulmonary Disease and Critical Care Medicine at Novant Health in Charlotte, North Carolina.
As you know, this is a very exciting time in pulmonary medicine, as our understanding of COPD management continues to evolve.
Today, we are going to discuss the critical needs in COPD and share the latest clinical data with a biologic for patients with COPD and an eosinophilic phenotype.
[Dr Smith]:
A link to the privacy policy can be found at the bottom of the page.
[Dr Miller]:
Before we begin, I’d like to emphasize GSK's commitment to transparency and education.
GSK believes in transparent scientific dialogue, with the goal of informing prescribers and caregivers about relevant clinical information related to GSK medicines and advancing care for patients, including those with COPD.
[Dr Miller]:
The program today includes evidence-based and balanced information that is consistent with the FDA-approved Prescribing Information.
This program is being sponsored by GSK, and we are receiving compensation for this event.
As physicians, we see the effects of COPD on our patients every day.
[Dr Miller]:
Even so, the data highlighted here really underscore the substantial burden of COPD on both patients and the healthcare system.
COPD affects nearly 16 million adults in the United States. As we know, patients frequently experience exacerbations, which can lead to emergency department visits and hospitalizations. These events can be life-changing for our patients.
[Dr Smith]:
These numbers truly illustrate the impact of COPD on patients and its contribution to rising healthcare costs. At the end of the day, we are all working toward preventing exacerbations, including those requiring steroids, antibiotics, or hospitalization, but for some patients, current treatments are not enough.
[Dr Miller to Dr Smith]:
Absolutely.
There are a lot of great medications available, but many patients continue to exacerbate despite maximal inhaled therapy.
[Dr Miller]:
These data are from a 52-week study evaluating inhaled maintenance treatments in patients with COPD who had a history of recent exacerbations.
About 50% of those receiving triple therapy still experienced at least one exacerbation in that year. This was also seen in patients receiving LAMA/LABA and ICS/LABA.
[Dr Miller to Dr Smith]:
Unfortunately, I think we all know these patients—we see them in the clinic every day. It’s especially challenging when patients are doing everything right: they are taking their medications as prescribed, not smoking, and being careful to avoid triggers. But they just keep having exacerbations.
[Dr Smith to Dr Miller]:
I completely agree.
It's incredibly frustrating for both the patients and for us as their physicians.
We wish we could be doing more for them.
Every patient has a different experience, of course, but I feel awful when I hear about my patients missing weddings, trips, and other family events because of their COPD.
On top of that, they assume they will be back to normal after an exacerbation, and when they don’t bounce back, they become very worried about having another one.
[Dr Miller to Dr Smith]:
Absolutely.
I find that some of my patients are reluctant to make plans and continue living their lives because of exacerbations. I had one patient who really wanted to visit his daughter abroad but was too nervous to book the trip.
[Dr Smith to Dr Miller]:
One thing that I can do when I see patients like these is to take a look at their blood eosinophil counts.
Blood eosinophils are an established biomarker in COPD. We used to think that COPD was driven solely by neutrophilic inflammation. However, it’s now known that about 40% of patients have an eosinophilic phenotype as determined by their blood eosinophils.
[Dr Smith]:
Identifying these patients is especially critical because they are at greater risk for exacerbations and related hospital visits.
The data on the right are from a retrospective study assessing COPD exacerbations in the year following a blood eosinophil measurement.
Patients with blood eosinophil counts of greater than 300 cells per microliter had up to a 76% greater risk of exacerbations and up to a 68% greater risk of hospitalizations and ED visits. This means that as many as 7 out of 10 patients with an eosinophilic phenotype are at greater risk for these events.
[Dr Smith]:
This is why I always check the blood eosinophil count in my patients with COPD, and I am not surprised when I see elevated eosinophils in those patients who are doing everything right but continue to have exacerbations.
[Dr Miller to Dr Smith]:
Exactly, it’s crucial to assess eosinophils in all of our patients with COPD to inform treatment approaches for preventing exacerbations, including those leading to hospital visits.
It is also important to remember that patients with an eosinophilic phenotype may have eosinophil counts within normal limits on the lab report. These values are unlikely to be highlighted or flagged as abnormal, so it can be easy to miss if we aren’t looking for it.
[Dr Miller]:
Another thing to consider is how these values are reported. We often talk about cutoffs for blood eosinophil counts, for example, greater than or equal to 300 cells per microliter but, most of the time, labs report the number differently. Instead of 300 cells per microliter, I usually see zero point three times ten to the third power cells per microliter, which means the same thing.
I think the main takeaway here is that blood eosinophils are a well-established biomarker in COPD that can help us identify patients at risk of exacerbations. We need to be checking those counts, especially in patients who are continuing to exacerbate despite triple inhaled therapy.
[Dr Smith to Dr Miller]:
I agree, it is so important to do what we can to prevent exacerbations, since these are significant life events for our patients.
Like we said earlier, we can end up in a place where we as physicians have done everything we can and the patients are doing their best, but they keep having exacerbations. And for so long there wasn’t anything else we could offer them.
[Dr Smith]:
That is why it is so exciting to be here today to talk about NUCALA.
NUCALA is indicated for the add-on maintenance treatment of adult patients with inadequately controlled COPD and an eosinophilic phenotype.
NUCALA is not indicated for the relief of acute bronchospasm and is contraindicated in patients with known hypersensitivity to mepolizumab or excipients.
[Dr Miller]:
Hypersensitivity reactions including anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, and rash have occurred. These generally occur within hours of administration but can have a delayed onset. Discontinue if a hypersensitivity reaction occurs.
NUCALA should not be used to treat acute symptoms or exacerbations of asthma or COPD, or acute bronchospasm.
Herpes zoster infections have occurred in patients receiving NUCALA. Consider vaccination if medically appropriate.
Do not discontinue systemic or inhaled corticosteroids abruptly when initiating NUCALA. Appropriate decreases in corticosteroid doses should be gradual and HCP supervised. Reduction in corticosteroid dose may be associated with withdrawal symptoms and/or unmask conditions previously suppressed by corticosteroid therapy.
Treat patients with pre-existing parasitic infections before initiating NUCALA. If patients become infected while receiving NUCALA and do not respond to anti-parasitic treatment, discontinue NUCALA until infection resolves.
Additional important safety information will be shared later in this program.
This is an exciting time to be in pulmonary medicine. I am so glad to have another option to offer appropriate patients.
[Dr Smith to Dr Miller]:
Absolutely. Let's talk a little bit about how NUCALA works.
[Dr Miller to Dr Smith]:
Certainly. NUCALA specifically targets IL-5, which inhibits signaling and reduces the production and survival of eosinophils. It is important to note that the mechanism of action has not been definitively established.
[Dr Smith]:
Let’s dive into the clinical data. NUCALA was evaluated in 2 pivotal trials, METREX and MATINEE. In both trials, patients were randomized 1:1 to once-monthly NUCALA or placebo, in addition to triple inhaled therapy. The primary endpoint was the annualized rate of moderate or severe exacerbations.
MATINEE was the longest phase 3 trial of any COPD biologic, with a duration of up to 2 years, and METREX was a 52-week study.
The eligibility criteria are detailed on the screen.
Notably, in both trials, patients were at least 40 years old, had a COPD diagnosis for at least 1 year, and had been on triple inhaled therapy, ICS/LABA/LAMA, for at least 3 months.
Patients also had moderate to very severe airflow limitation and least 2 moderate exacerbations or 1 severe exacerbation in the past year.
Regarding blood eosinophil counts, the efficacy population in METREX included patients with a blood eosinophil count of at least 150 cells per microliter at screening or at least 300 cells per microliter in the prior year. In MATINEE, patients were required to have a blood eosinophil count of at least 300 cells per microliter at screening and at least 150 cells per microliter in the prior year.
Smoking and asthma history criteria also differed slightly between trials, as noted here.
Ultimately, I think an important takeaway is that these trials included patients similar to those we see in the clinic daily.
[Dr Miller]:
That’s right, NUCALA was studied across a wide spectrum of patients with COPD.
Both trials included patients with and without chronic bronchitis, GOLD grades 2 through 4, and all mMRC dyspnea grades.
METREX also included patients regardless of their smoking status and with a blood eosinophil count at or above 150 cells per microliter at screening.
So NUCALA wasn't just studied in patients with blood eosinophil counts off the charts.
This really highlights the wide range of patients that NUCALA was studied in.
[Dr Smith]:
Here is the breakdown of baseline characteristics in MATINEE and METREX. Overall, 42% of patients studied were younger than 65 years old.
As you can see, these data are not just limited to much older patients who won’t quit smoking.
So, how did this group of patients do on NUCALA?
[Dr Miller]:
In MATINEE, NUCALA significantly reduced moderate or severe exacerbations by 21% compared with placebo. Similarly, in METREX, the exacerbation rate was reduced by 18% with NUCALA versus placebo.
When I see these data, I think about the possibility of preventing 1 out of 5 exacerbations, which is especially important for our patients.
[Dr Smith to Dr. Miller]:
Absolutely, these are great data. When we think back to those patients we’ve been discussing, this could make a real difference for them.
[Dr Miller]:
As we have just seen, MATINEE and METREX met their primary endpoints. Here, we see that NUCALA also reduced exacerbations requiring hospitalization or an ED visit by 35% compared with placebo in MATINEE. This secondary endpoint result was not statistically significant due to failure earlier in the testing hierarchy.
It is interesting to see this type of data. Hospitalizations and ED visits are something we as physicians care a lot about.
Thinking about the exacerbation reduction data, what do you think this could mean for appropriate patients with COPD?
[Dr Smith to Dr. Miller]:
I think this is an impactful development in COPD management. As we mentioned earlier, these events are typically significant, and I am glad I have another option to offer my patients.
For them, it isn’t just about the time that they are stuck at home or in a hospital bed. It’s also the long recovery that comes after the exacerbation. These patients often feel the effects for months, continue to miss out on their life events, and may never return to their baseline. So, having a treatment option that could help prevent the next exacerbation is something I am really excited about.
[Dr Miller]:
I totally agree with you: preventing exacerbations, including those that require steroids, antibiotics, or hospitalizations, is one of the main goals.
[Dr Smith]:
Earlier, we talked a lot about the wide spectrum of patients studied in the NUCALA COPD trials. Over the next few slides, we will look at moderate or severe exacerbation rates in different patient subgroups in MATINEE.
Here, we have data from the prespecified subgroup analysis across the GOLD grades of airway obstruction.
Patients treated with NUCALA who had moderate airflow obstruction, or GOLD 2, had a reduction of 15%, those with severe airflow obstruction, or GOLD 3, had a 27% reduction, and those with very severe airflow obstruction, or GOLD 4, had a reduction of 19% compared with placebo. Please note that all results are descriptive.
[Dr Miller]:
I find these data quite interesting. It's nice to see exacerbation rates across these groups, especially in patients with GOLD 4, who have a post-bronchodilator FEV1 of less than 30% predicted and are not always included in clinical trials.
[Dr Miller]:
When looking across smoking status, we see that former smokers had an 18% reduction with NUCALA compared with placebo and there was a 32% reduction with NUCALA in patients who were current smokers. These results are descriptive.
[Dr Miller to Dr Smith]:
I'm glad to see data in current smokers.
[Dr Smith to Dr Miller]:
I agree. We often think about how smoking causes an inflammatory response, but it’s good to see data like this in former smokers too.
[Dr Miller]
Lastly, we are looking at moderate or severe exacerbation rates across COPD subtypes.
When comparing NUCALA and placebo in a post hoc analysis, there was a 31% reduction in patients with chronic bronchitis, an 18% reduction in patients with emphysema and in patients with both chronic bronchitis and emphysema, and a 9% reduction in patients reported as having neither subtype identified. All results are descriptive.
I think these data are interesting. Many of my patients have emphysema, so, for me, it is nice to see data in this population.
[Dr Smith]:
We know that COPD can significantly impact our patients’ quality of life.
Here we are looking at SGRQ data, a validated measure of patient-reported quality of life. The SGRQ-C is a variation of this questionnaire for patients with COPD.
In MATINEE, 50% of patients had a clinically important difference in total SGRQ with NUCALA versus 46% with placebo at Week 52. As you can see on the slide, the data from METREX were similar.
In MATINEE, the change from baseline in total SGRQ was −5.7 with placebo and −8.0 with NUCALA at Week 52. The minimum clinically important difference for change in the SGRQ score is 4 points.
All results presented on this slide are descriptive only, so no conclusions can be drawn.
[Dr Miller]:
We also know that patients with COPD tend to lose lung function year-over-year, so it is important to see what these data look like in this population.
Here, we are looking at the change from baseline in prebronchodilator FEV1. We see that both treatment groups had an increase of about 50 milliliters at Week 24 and just over 30 milliliters at Week 52.
Looking at the data for Weeks 76 and 104, we can appreciate that patients on NUCALA had increases of approximately 59 and 45 milliliters from baseline, whereas the placebo group had a decline in lung function that returned to baseline by Week 104. All of these results are also descriptive, so no conclusions can be made here.
Now, let's shift to the safety data from these trials.
[Dr Smith]:
NUCALA has a well-established safety profile based on the data from 3 phase 3 trials, which included more than 2000 patients with COPD, making it the largest patient population studied for a COPD biologic.
The most common adverse reactions in the pooled data from these studies are listed here. The most frequent in patients receiving NUCALA were back pain at 7% and diarrhea and cough at 5%.
Herpes zoster events were reported in 1% of the patients with NUCALA and 0.7% with placebo.
As shown previously, the most common adverse reactions observed in at least 5% of patients in the NUCALA treatment arm were back pain, diarrhea, and cough.
The data on pregnancy exposures are insufficient to inform us of the drug-associated risk.
Monoclonal antibodies are transported across the placenta as pregnancy progresses; potential effects on a fetus are likely to be greater during the second and third trimesters.
[Dr Miller]:
Now that we have discussed the established safety profile of NUCALA, let's talk about how it is administered. NUCALA offers a simple once-monthly dosing schedule, which is half as many doses per year as the other biologic option.
This treatment can be taken every 4 weeks at home or in the office to allow flexibility for each patient.
[Dr Smith]:
As we wrap up today, let's review the information we should remember as we head into clinic tomorrow. These key takeaways include unmet needs in COPD and efficacy and safety results with NUCALA.
As we see here, NUCALA helped prevent exacerbations. In MATINEE, NUCALA significantly reduced moderate or severe exacerbations per year by 21% versus placebo.
NUCALA helped reduce hospital visits due to exacerbations. Please note that these data were not statistically significant.
And lastly, NUCALA offers a simple, once-monthly dosing schedule to fit into the cadence of our patients’ lives.
[Dr Smith to Dr Miller]:
What are your thoughts, Andrew?
[Dr Miller to Dr Smith]:
I think we need to be proactive at identifying patients who could benefit from NUCALA.
I recommend getting a blood eosinophil count for all patients with COPD and checking in the EMR for those historic labs, as these data may already be available.
[Dr Miller]:
And remember, a blood eosinophil count of 150 cells per microliter won’t be automatically flagged as abnormal, so it is critical to review the lab work to identify appropriate patients, especially for those who continue to exacerbate despite triple therapy.
[Dr Smith to Dr Miller]:
That’s a good point!
This has been a great discussion. Thank you so much for joining us.
[Dr Miller]:
Thank you everyone. It's been a pleasure.
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