COPD is a progressive lung disease characterized by airflow limitation. Exacerbations, both moderate and severe, can lead to a decline in lung function, particularly FEV-1 (Forced Expiratory Volume in 1 second)&nbsp;1,2.

GOLD Group E patients, according to the GOLD (Global Initiative for Chronic Obstructive Lung Disease) classification, are those with a high risk of exacerbations and more symptoms, often experiencing a faster decline in lung function and quality of life&nbsp;3.

FEV-1, or Forced Expiratory Volume in 1 second, is a key measurement in lung function testing. It represents the volume of air a person can forcefully exhale in the first second after a deep breath.
 
 Lung function decline (FEV-1) in COPD patients increases mortality risk, whereas improvement resets the patient’s baseline and lowers exacerbation risk.

BOREAS and NOTUS outcomes are breakthrough for COPD patients, showing statistically significant and clinically meaningful improvements in moderate and severe exacerbation reduction, lung function over 52 weeks4,5.
&nbsp;
These 2 trials have been conducted on approx. 2000 patients and its endpoints were designed according to the GOLD standards4,5.

Dupixent's significantly proven reduction of Moderate and Severe exacerbations6:

In both BOREAS and NOTUS, Dupixent + background therapy has demonstrated statistically significant reductions in moderate and severe exacerbation rate up to 34%, as shown in the NOTUS trial, vs. placebo + background therapy.

white

<div>
 <div>
 Dupixent's statistically significant FEV-1 improvement6:
 </div>
</div>

<div>
 <div>
 In both BOREAS and NOTUS, Dupixent demonstrated early and significant FEV-1 improvement vs. placebo + background therapy over 52 weeks.
 </div>
</div>

<div>
 <div>
 DUPIXENT + BG therapy has demonstrated a notable improvement in lung function vs. placebo + BG therapy, in particular has shown:
 </div>
</div>

Early onset
 
 (e.g., measurable effect already after 2 weeks in BOREAS)

Sustained effect
 
 over 52 weeks in BOREAS

Significant FEV-1 improvement
 
 at week 52 in both trials

A meta-analysis (52 studies; 62,385 patients) demonstrated significant correlations between mean trough FEV-1 and HRQOL in patients with stable COPD 1,2

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="background-color: rgb(153, 204, 0);">
 <ul>
 <li>An MCID improvement in FEV-13&nbsp;corresponded to a larger than MCID improvement in measures of HRQOL (SGRQ)4 and breathlessness (TDI)4 
 &nbsp;</li>
 <li>Analyses of follow-up data at 6 and 12 months suggest that the correlation of trough FEV-1 with HRQOL (SFRQ and TDI) strengthens with time.</li>
 </ul></td>
 </tr>
 </tbody>
</table>
<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="background-color: rgb(0, 153, 102);">
 The correlation between FEV-1 and QoL enhancement, coupled with the significant FEV-1 improvement (+153mL vs. baseline) achieved with Dupixent, further reinforce the robustness of SGRQ improvement results.</td>
 </tr>
 </tbody>
</table>

Dupixent has proven to show consistent results across subpopulations in both BOREAS and NOTUS trials6:

In the BOREAS trial, Dupixent demonstrated consistent clinical benefit in terms of moderate or severe exacerbation reduction and lung function (i.e., FEV-1 change vs. placebo) results across study subgroups.

In the NOTUS trial, Dupixent demonstrated consistent clinical benefit in terms of moderate or severe exacerbation reduction and lung function (i.e., FEV-1 change vs. placebo) results across study subgroups.

References

Proven Efficacy of Dupixent® in COPD

PAYOR

OUT-OF-TAXONOMY

COPD is associated with persistent respiratory symptoms, exacerbations, and inflammation, which contribute to declines in lung function, reduced QOL, and high mortality.

Persistent symptoms of COPD contribute to&nbsp;patients’ physical debilitation1.
In 2017, COPD was the&nbsp;sixth leading cause of disability-adjusted life years (DALYs)&nbsp;worldwide and accounted for the majority of DALYs associated with chronic respiratory disease2,3

I am continually tired. The simplest tasks take ages to complete and leave me exhausted, breathless, and depressed.
Not being able to breathe and unable to do physical activity. The worst part: Your mind tells you that you can do it.

ASSESS was an observational study which enrolled patients with stable COPD in clinical practice and aimed to investigate the relationship between 24-hour symptoms and other patient-reported outcomes4.
Persistent symptoms of COPD were associated with&nbsp;high levels of anxiety and depression, and poor sleep quality,&nbsp;irrespective of whether symptoms occurred in the early morning, daytime, or night time4.
Patients who experienced symptoms throughout the whole 24-hour day experienced the worst levels of impairment4.
Mean anxiety, depression, and sleep quality scores according to the pattern of COPD symptoms throughout the 24 hour day (n=727)4

Anxiety

Depression

Sleep Disturbance

*0-7 = normal; 8-10 = mild; 11-15 = moderate; 16-21 = severe. Higher scores mean worse sleep quality., 
 CASIS, COPD and Asthma Sleep Impact Scale; HADS, Hospital Anxiety and Depression Scale.
Quality of Life

Persistent debilitating symptoms of COPD have a substantial impact on patients' QoL.
A cross-sectional European observational study illustrated QoL impairment was related to COPD severity:
As disease severity increased,&nbsp;QoL impairment increased, as measured using SGRQ scoress5.
Factors associated with worsening QoL include5:
<ul>
 <li>
 COPD symptoms of breathlessness</li>
 <li>
 Cough and excess sputum</li>
 <li>
 Exacerbations</li>
 <li>
 Lung function decline</li>
 <li>
 Hospitalizations</li>
</ul>

Impairment in QoL related to COPD severity:Data from a cross-sectional European studys5

In many patients,&nbsp;guilt&nbsp;or&nbsp;shame&nbsp;from their perception of COPD as a "self-inflicted" disease can effect their QoL and interaction with HCPs1.
The MIRROR study was conducted in Europe and analysed how perceptions of disease severity and impact on QOL may differ between patients and HCPs. This study found that6:
<ul>
 <li>~90%&nbsp;of patients said they were&nbsp;"not completely frank"&nbsp;when talking to clinicians 
 &nbsp;</li>
 <li>49-53%&nbsp;of primary care doctors and pulmonologists seem to be aware of this but&nbsp;underestimate&nbsp;the extent to which it impacts clinician-patient interactions1</li>
</ul>

black

Clinical burden of co-existing conditions in COPD
The inflammatory processes associated with COPD may affect the functioning of extrapulmonary systems, and as a result, COPD patients present with co-existing diseases across a range of organ systems7. This can greatly increase the burden of COPD.
In a retrospective analysis of 14,603 Dutch patients with COPD, 88% had ≥1 co-existing disease7

*The consideration of asthma as a separate co-existing disease from COPD is controversial.
CRS, chronic rhinosinusitis; AF, atrial fibrilation; CHD, coronary heart disease; GERD, gastroesophageal reflux disease; PVD, peripheral vascular disease; TIA, transient ischemic attack.
COPD with co-existing conditions is associated with negative health impact, worse treatment management:

<ul>
 <li>Patients with COPD and co-existing diseases, such&nbsp;as heart failure, osteoporosis/osteopenia, and asthma have an increased risk of frequent exacerbations7</li>
 <li>COPD and co-existing Asthma also result in increased hospital admissions, whereas COPD and cardiovascular disease has a higher rate of hospitalization and death8,9</li>
</ul>

Health Impact

<ul>
 <li>30% of patients with COPD and Asthma have ≥2 records of OCS dispensing over their lifetime vs. 12%&nbsp;of patients with COPD alone10</li>
 <li>Short&nbsp;and long-term OCS use has been linked to multiple&nbsp;adverse-events11</li>
</ul>

Worse treatment management

Exacerbations
Patients with COPD can experience "flare-ups", which can be defined as general worsening of symptoms as well as more serious exacerbations.
An exacerbation of COPD is defined as an event characterized by&nbsp;increased dyspnea and/or cough and sputum that worsens in &lt;14 days which may be accompanied&nbsp;by tachypnea and/or tachycardia and is often associated with increased local and systemic inflammation caused by infection, pollution, or other insult to the airways12.
Exacerbations can be mild, moderate and severe. Severe exacerbations usually require hospitalisation13.
Exacerbations of COPD significantly impact on the health status of a patient, increase the rate of lung function decline, and worsen the prognosis of patients.
Quality of life
In a study of 70 COPD patients, SGRQ total and component scores — a tool used to measure quality of life-were significantly higher in the frequent exacerbator group compared with those who less frequently experienced exacerbations23.

Relationship between SGRQ score and exacerbation frequency14
<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td>Exacerbation frequency</td>
 <td>n</td>
 <td>SGRQ total score</td>
 <td>SGRQ 
 component: Symptoms</td>
 <td>SGRQ 
 component: Activities</td>
 <td>SGRQ 
 component: Impact</td>
 </tr>
 <tr>
 <td>0-2</td>
 <td>32</td>
 <td>48.9 ± 15.6</td>
 <td>53.2 ± 17.2</td>
 <td>67.7 ± 17.2</td>
 <td>36.3 ± 18.2</td>
 </tr>
 <tr>
 <td>3-8</td>
 <td>38</td>
 <td>64.1 $ 14.6</td>
 <td>77.0 $ 15.8</td>
 <td>80.9 $ 16.0</td>
 <td>50.4 ‡ 17.6</td>
 </tr>
 <tr>
 <td>Mean difference</td>
 <td>&nbsp;</td>
 <td>-15.1</td>
 <td>-21.9</td>
 <td>-12.2</td>
 <td>-14.1</td>
 </tr>
 <tr>
 <td>95% CI</td>
 <td>&nbsp;</td>
 <td>-22.3 to -7.8</td>
 <td>-29.7 to -14.0</td>
 <td>-21.2 to -5.3</td>
 <td>-22.9 to -5.6</td>
 </tr>
 <tr>
 <td>P value</td>
 <td>&nbsp;</td>
 <td>0.0005</td>
 <td>0.0005</td>
 <td>0.001</td>
 <td>0.002</td>
 </tr>
 </tbody>
</table>

Mortality
In a study of 73,106 COPD patients,&nbsp;the risk of death increased with each successive severe exacerbation experienced.
The rate of death after the second severe exacerbation was&nbsp;1.9x&nbsp;higher than after the first, while after the 10th it was&nbsp;5x&nbsp;higher than after the first15.
HR for death increases with every successive severe exacerbation15

Lung function
The UPLIFT study of 5,992 COPD patients observed that a higher frequency of severe hospitalized COPD exacerbations was associated with a&nbsp;marked decline in lung functions16.
Mean change in lung function parameters by increasing frequency of hospitalized exacerbations in the 4-year UPLIFT study16

Exacerbations were defined as an increase in or the onset of more than one respiratory symptom (cough, sputum, sputum purulence, wheezing, or dyspnea) lasting 3 days or more and requiring treatment with an antibiotic or systemic corticosteroids.
BD, bronchodilator; FVC, forced vital capacity; SE, standard error.

Disease onset, course, and severity
COPD can start early in life and take a long time to manifest clinically. As identifying early COPD can be difficult, patients are typically diagnosed with COPD aged &gt; 40 years&nbsp;12,13.
Morbidity due to COPD increases with age: 
 As lung function declines with age, patients experience more exacerbations, which increases the risk of future exacerbations and the rate of lung function decline12.

Clinical Burden of COPD

Chronic Obstructive Pulmonary Disease (COPD) is a progressive lung condition characterized by breathing difficulties, with significant impacts on patients' quality of life.
Global Impact

Global Death Toll:
<ul>
 <li>Globally, COPD is the&nbsp;third leading cause of death,&nbsp;following ischemic heart disease and stroke1</li>
 <li>In 2019 alone, it caused&nbsp;3.23 Million deaths worldwide,&nbsp;representing&nbsp;6% of total global deaths1,2.</li>
</ul>

Widespread Prevalence:
<ul>
 <li>Approximately&nbsp;299.4 Million cases&nbsp;were reported globally in 2017, showing a&nbsp;24%&nbsp;increase since 20073.</li>
 <li>The&nbsp;prevalence of COPD is projected to increase, with an estimated&nbsp;5.4 Million deaths by 20604. &nbsp;</li>
</ul>

DALYs:
<ul>
 <li>COPD accounts for the majority of Disability-Adjusted Life Years (DALYs) among chronic respiratory diseases5, causing 2.6% of global DALYs in 20156.</li>
</ul>

<h3>COPD Burden in Kingdom of Saudi Arabia</h3>
COPD presents a significant health challenge with&nbsp;rising prevalence rates and economic impact:
<ul>
 <li>
 COPD prevalence&nbsp;increased by&nbsp;49%&nbsp;from 1990 to 2019, with&nbsp;2,053 cases&nbsp;per 100,000 people reported in 20197.</li>
 <li>
 Mortality Impact:&nbsp;COPD accounts for about&nbsp;1.65%&nbsp;of all-cause deaths8.</li>
 <li>
 Macroeconomic Impact:&nbsp;According to the World Bank, the estimated economic loss attributed to COPD in 2017 was approximately&nbsp;$12.497 Billion, reflecting the long-term economic consequences of unmanaged COPD in the region9.</li>
</ul>

<h3>Costs of Treatment and Care in Kingdom of Saudi Arabia:</h3>

Direct Costs:
Healthcare Expenditures:&nbsp;COPD is one of the non-communicable diseases (NCDs) contributing to Saudi Arabia's healthcare expenditures, which amount to&nbsp;SAR 66 Billion&nbsp;annually10.
Hospitalization and Treatment:&nbsp;The direct costs associated with COPD primarily include expenses related to hospitalization and treatment of exacerbations. These costs are significant drivers of healthcare spending11-12.

Indirect Costs
Productivity Losses:&nbsp;The indirect costs of COPD include reduced workforce participation and loss in national productivity due to premature mortality, disability, and workplace losses. These losses are valued at&nbsp;SAR 25.6 Billion annually10.

Productivity claims associated with COPD were responsible for 10% of the overall COPD cost burden for working patients13:

Productivity Losses:
<ul>
 <li>Frequent exacerbators experience the highest productivity loss: 456.5</li>
 <li>Infrequent exacerbators have a significant loss as well: 361.8</li>
 <li>Non-exacerbators show the lowest productivity loss: 255.4</li>
</ul>
→ Exacerbations directly correlate with increasing productivity losses.

Lost Work Time (sick leave):
<ul>
 <li>Frequent exacerbators also show the highest amount of lost work time: 60.0</li>
 <li>Non-exacerbators experience less time away from work: 49.8</li>
 <li>Infrequent exacerbators fall in between: 60.0</li>
</ul>
→ Exacerbations are key drivers of absenteeism in COPD patients.

Decreased Productivity (Presenteeism)
<ul>
 <li>Frequent exacerbators suffer a higher loss in productivity while at work: 29.3</li>
 <li>Non-exacerbators: 11.4</li>
</ul>
→ Exacerbations are key drivers of absenteeism in COPD patients.

COPD treatment not only affects productivity of patients, but also of the caregivers: 
A Spanish study analyzed the burden borne by informal caregivers (n=220,892) of patients with COPD14.

% of informal caregivers (of COPD patients) with health-, 
 professional-,and leisure/social-related problems

% of informal caregivers of COPD patients having problems 
 vs. caregivers of patients with other chronic diseases

Caregivers face severe challenges: 
<ol>
 <li>83% of caregivers report leisure/social-related problems, followed by 38% experiencing professional-related problems and 35% facing health issues. 
 &nbsp;</li>
 <li>COPD caregivers, more than those of other chronic diseases like stroke or myocardial infarction, face greater deterioration of health and a marked decrease in leisure time. 
 &nbsp;</li>
 <li>The comparison with caregivers of other chronic diseases further emphasizes the unique burden COPD imposes, showing higher rates of decreased leisure time and overall strain on caregivers.</li>
</ol>

Economic Burden of COPD in KSA

Mechanism of Action
Dupixent has emerged as a groundbreaking therapeutic option for various type 2 inflammatory diseases. As a fully human monoclonal antibody, Dupixent uniquely inhibits the signaling of both interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways, key drivers of type 2 inflammation 1,2.

Figure 1: DUPIXENT is the only dual inhibitor of IL-4 and IL-13 signaling3
This mechanism of action has demonstrated&nbsp;significant clinical benefits across multiple indications, including Atopic Dermatitis, Asthma, Chronic Rhinosinusitis with Nasal Polyposis, Eosinophilic Esophagitis, Prurigo Nodularis and most recently, Chronic Obstructive Pulmonary Disease2&nbsp;with regulatory approvals in&nbsp;&gt;60 countries and over 1,000,000 patients treated globally1.
Dupixent has rapidly become an essential therapy in the management of type 2 inflammatory diseases and has&nbsp;demonstrated sustained improvement in symptoms&nbsp;across various indications, with&nbsp;long-term safety data&nbsp;available for&nbsp;up to 5 years&nbsp;in some conditions&nbsp;1,2.
This unique mechanism of action has demonstrated significant clinical benefits across multiple type 2 inflammatory diseases as seen in the 3 examples below:
Atopic Dermatitis (AD):

1.Mechanism of Action: 
 Targeting of&nbsp;IL-4&nbsp;and&nbsp;IL-13&nbsp;signaling, key drivers of type 2 inflammation in AD4

2.Long-term Efficacy: 39% 
 Achieved IGA score of 0-1 (clear/ almost clear) with a reduction of ≥2 points on a 0-4 IGA scale at 16 weeks in adults® 42.7% 
 Had an IGA score of 0/1 (clear/almost clear) by week 52 in adolescents (12-17 years)5

Sustained improvement in skin clearance up to 52 weeks in adults®

3. Real-World Evidence: 5-year clinical trial data&nbsp;and experience in&nbsp;&nbsp;&gt; 1,000,000 
 patients worldwide across all indications have proven Dupixent's efficacy*

Approved for use in patients as young as 6 months old5

1.Mechanism of Action: 
 Targeting of&nbsp;IL-4&nbsp;and&nbsp;IL-13&nbsp;signaling, reducing Type 2 Inflammation in airways4,6

2.Long-term Efficacy: 
 Up to 3 years of data show&nbsp;sustained&nbsp;improvment in lung function and reduction in severe exacerbations4,7 13-22% 
 Improvement in lung function (FEV-1) at 96 weeks&nbsp;4

3. Real-World Evidence: 
 &nbsp;&gt; 2,200 patients&nbsp; 
 Enrolled in the Phase 3 open-label extension trial making it the largest biologic medicine trial in Asthma4,8

Chronic Obstructive Pulmonary Disease (COPD):

1.Mechanism of Action: 
 Targeting of&nbsp;IL-4&nbsp;and&nbsp;IL-13&nbsp; 
 pathways to reduce Type 2&nbsp; Inflammation in COPD7

2.Long-term Efficacy: 30% and 34% 
 Annualized rate of moderate or severe COPD exacerbations over 52 weeks in BOREAS and NOTUS trial7

Improvements in lung function (FEV-1) observed as early as week 2 and sustained at 52 weeks7

Enhanced health-related quality of life7

3. Real-World Evidence: 1st&nbsp; 
 new treatment approach for COPD in more than a decade7

Approved for ~220,000 adults in the European Union7

In Conclusion
Dupixent (dupilumab) has proven to be a transformative treatment option for multiple type 2 inflammatory diseases by targeting IL-4 and IL-13 pathways.
Its efficacy across diverse indications demonstrates significant improvement in patient outcomes, reducing exacerbation rates, enhancing lung function, and improving skin clarity and quality of life.
Long-term data highlight its consistent safety profile across various age groups, further supported by real-world evidence.
Dupixent remains a promising therapy for sustained disease control and relief from the burdens of type 2 inflammation.

Proven Efficacy of Dupixent® against Type 2 Inflammation

Dupixent has emerged as a significant therapeutic option for the treatment of various type 2 inflammatory diseases. As a fully human monoclonal antibody that inhibits interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, Dupixent offers a targeted approach to managing conditions such as Atopic Dermatitis, Asthma, Chronic Rhinosinusitis with Nasal Polyposis, and Eosinophilic Esophagitis and COPD1.
Mechanism of Action and Safety Implications
Dupixent's unique action as an immunomodulator, rather than a broad immunosuppressant, supports its positive safety profile. By targeting IL-4 and IL-13 pathways specifically, Dupixent provides immune response control without significantly compromising immune defenses, which may lower the risk of serious infections often seen with other immunosuppressive treatments.
Inhibition of IL-4 and IL-13 signaling has a substantial impact on Type 2 inflammation diseases as it helps reduce the inflammation by2:
<ol>
 <li>Helping reduce Itch: May break itch-scratch cycle and reduce nerve sensitization</li>
 <li>Helping achieve nodule clearance: Reduce skin fibrosis</li>
</ol>

Figure 1: DUPIXENT is the only dual inhibitor of IL-4 and IL-13 signaling2
Long-Term Safety Data
Dupixent's safety has been confirmed through studies extending&nbsp;up to five years, covering over&nbsp;800,000 patients&nbsp;globally.

The LIBERTY AD OLE trial, a long-term extension study, highlighted the&nbsp;tolerability of Dupixent&nbsp;in patients with moderate to severe atopic dermatitis&nbsp;over a five-year period. 
 This trial, involving 2,677 patients, found that&nbsp;the safety profile remained consistent with earlier controlled trials1.

Common Adverse Events
Common adverse effects seen across trials include injection site reactions, conjunctivitis (more common in those with atopic dermatitis), nasopharyngitis, headache, and back pain.
In recent COPD trials, adverse effects with a frequency of ≥5% included COVID-19 infection and diarrhea compared to placebo3,4.

Safety by Indication

2%&nbsp;of TEA leading to permanent Dupixent discontinuation vs 8% for placebo5

3%&nbsp;of TEA leading to permanent Dupixent discontinuation vs 6% for placebo6

4%&nbsp;of TEA leading to permanent Dupixent discontinuation vs 11% for placebo7

Most TAEAs mild or moderate8

Similar incidences of TEAEs in patients treated with DUPIXENT vs placebo arm (64% and 57% respectively)9

Regulatory Perspective and Approvals
Regulators like the U.S. FDA and the European Medicines Agency (EMA) have reviewed comprehensive safety data, concluding that Dupixent's benefits outweigh associated risks, which has led to approval in over 60 countries. The consistent safety profile across various inflammatory conditions has supported regulatory endorsements1.
Special Considerations

Pediatric Use: 
 Dupixent has shown a favorable safety profile in younger patients, receiving approval for certain conditions in patients as young as 6 months old1.

Minimal Immunosuppression: 
 Unlike many biologic therapies, Dupixent does not broadly suppress the immune system, contributing to its positive long-term safety profile1.

Monitoring Needs: 
 Dupixent does not require initial or ongoing laboratory testing, highlighting its low risk of serious systemic effects. 
 &nbsp;

Clinical trial and post-market data affirm Dupixent's consistent and favorable safety profile across multiple type 2 inflammatory diseases. 
 Its targeted action and generally mild side effects underscore its strong benefit-risk profile. 
 Dupixent's safety has been maintained across different age groups and in extended use, with no significant safety issues arising in long-term studies. 
 Current evidence supports its use as a safe and effective option for patients with type 2 inflammatory diseases.

Conclusion

Proven Safety of Dupixent® against Type 2 Inflammation

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="text-align: center;">Examine patients with LGMW and/or hyperCKemia and undiagnosed muscle biopsy for LOPD</td>
 </tr>
 <tr>
 <td style="text-align: center;">
 <h3>⬇</h3></td>
 </tr>
 <tr>
 <td style="text-align: center;">Inclusion criteria: 
 Inconclusive LGMW with undiagnosed muscle biopsies</td>
 </tr>
 <tr>
 <td style="text-align: center;">
 <h3>⬇</h3></td>
 </tr>
 <tr>
 <td style="text-align: center;">
 Of the&nbsp;340&nbsp;evaluated muscle biopsies,
 69&nbsp;fulfilled the inclusion criteria</td>
 </tr>
 <tr>
 <td style="text-align: center;">
 <h3>⬇</h3></td>
 </tr>
 <tr>
 <td style="text-align: center;">Testing: 
 DBS+enzyme activity of GAA</td>
 </tr>
 </tbody>
</table>

<h2>Results</h2>
<h3 style="text-align: center;">Baseline characteristics of patients with unclassified LGMW</h3>

Median age 51&nbsp;years

Median symptom onset 6&nbsp;years

<h3 style="text-align: center;">Clinical and laboratory data of patients with unclassified LGMW</h3>

Median DBS GAA activity: 1.18 nmol/punch×21 hours
Reduced GAA activity was identified through enzyme kinetic testing in two patients

Myopathic symptoms

Laboratory results

<table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td colspan="3">
 <h3 style="text-align: center;">Diagnostic yield of LOPD: 2/69 (2.9%)</h3></td>
 </tr>
 <tr>
 <td style="text-align: center;">Patient 1</td>
 <td style="text-align: center;">&nbsp;</td>
 <td style="text-align: center;">Patient 2</td>
 </tr>
 <tr>
 <td style="text-align: center;">A 22-year–old Caucasian female with the chief complaint of muscular exertion intolerance associated with muscle aches and cramps.</td>
 <td>
 <table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="text-align: center;">Patient profile</td>
 </tr>
 </tbody>
 </table></td>
 <td style="text-align: center;">A 29-year–old Caucasian male with atrophies of the shoulder, pelvic girdle, and paravertebral muscles. Predominantly left-sided scapula alata and positive Gower’s sign.</td>
 </tr>
 <tr>
 <td style="text-align: center;">Completely unspecific myopathic changes with evidence of small lipid droplets</td>
 <td style="text-align: center;">
 <table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td>Muscle biopsy</td>
 </tr>
 </tbody>
 </table></td>
 <td style="text-align: center;">
 <ul>
 <li style="text-align: left;">Suspicious changes associated with Pompe disease</li>
 <li style="text-align: left;">Vacuolated muscle fibers</li>
 <li style="text-align: left;">Glycogen storage with enhanced lysosomal activity</li>
 </ul></td>
 </tr>
 <tr>
 <td style="text-align: center;">No signs of HCM, FVC: &lt;80%</td>
 <td style="text-align: center;">
 <table border="1" cellpadding="10" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td>
 Other findings</td>
 </tr>
 </tbody>
 </table></td>
 <td style="text-align: center;">No signs of HCM, FVC: 72%</td>
 </tr>
 <tr>
 <td colspan="3">
 <h3 style="text-align: center;">LOPD not only demonstrates wide variability in the clinical phenotype but also in the histopathological changes in the skeletal muscles.</h3></td>
 </tr>
 </tbody>
</table>

Revisiting muscle biopsies is important in neuromuscular disease diagnosis.

Muscle biopsy can aid in LOPD identification, but glycogen-related vacuolation can be absent.

An inconclusive muscle biopsy does not rule out Pompe disease.

DBS evaluation should precede muscle biopsy for all LGMW patients

Abbreviations

Reference

Prevalence Of LOPD In Patients With Undifferentiated Proximal Myopathy And Undiagnosed Muscle Biopsy

POMPE

RARE-DISEASE

<h2>The Continuous burden of Atopic Dermatitis can have far-reaching Impact</h2>
The burden of inadequately controlled atopic dermatitis may become chronic, or even cumulative, impacting patients throughout their lives1,2

~70 - 80%&nbsp;of atopic dermatitis patients develop additional type 2 inflammatory diseases, such as asthma or allergic rhinitis, which correlate with atopic dermatitis severity5,6
*The age of children included in the Eczema Society of Canada Atopic Dermatitis Quality of Life Report survey ranged from 0 to 18 years

~70 - 80%&nbsp;of atopic dermatitis patients develop additional type 2 inflammatory diseases, such as asthma or allergic rhinitis, which correlate with atopic dermatitis severity5,6
* The age of children included in the Eczema Society of Canada Atopic Dermatitis Quality of Life Report survey ranged from 0 to 18 years

~70 - 80%&nbsp;of atopic dermatitis patients develop additional type 2 inflammatory diseases, such as asthma or allergic rhinitis, which correlate with atopic dermatitis severity5,6
* The age of children included in the Eczema Society of Canada Atopic Dermatitis Quality of Life Report survey ranged from 0 to 18 years

<h2>Around 3 in 5 adult Moderate-to-Severe Atopic Dermatitis patients are Inadequately controlled despite treatment1*</h2>

A chronic, inadequately controlled disease driven by persistent underlying inflammation7,8

Patients may experience intensified disease activity for 30–50% of the year2

Current treatment paradigm (OCS/ immunosuppressants) primarily addresses disease manifestation using a reactive, episodic approach9

Length of treatment with systemic steroids and other immunosuppressants is limited by common side effects and chance of rebounds11

<h2>Continuous treatment of underlying Inflammation is warranted for Long-term disease control10</h2>

A more sustainable treatment paradigm proactively targets the persistent underlying inflammation with a safety profile that allows for continuous treatment10-12

Adequately controlled disease with long-term improvements in signs, symptoms, and quality of life.

<h2>Dysregulation of the Type 2 Immune Response pathway leads to Underlying Type 2 Inflammation in Atopic Dermatitis and other Type 2 Inflammatory diseases*</h2>

Primary immune cells1-3 
 &nbsp;

Key cytokines1-4 
 &nbsp;

Associated intracellular signaling pathway4,5 
 &nbsp;

Natural defensive roles against:1,3,6 
 &nbsp;

Associated diseases when dysregulated7-8 
 &nbsp;

Viral infection 
 Intracellular bacterialinfection 
 Cancer cells

Psoriasis 
 Psoriatic arthritis

Allergens 
 Parasites 
 &nbsp;

Atopic dermatitis 
 Asthma 
 CRSwNP

Extracellular bacteria 
 Fungi 
 &nbsp;

Psoriasis 
 Psoriatic arthritis

*Simplified depiction based on key published information; not meant to be exhaustive in nature.

<h2>In Atopic Dermatitis, Type 2 Inflammation is always present throughout the body,even in nonlesional or normal-looking skin1–3</h2>
<ul>
 <li>Dysregulation of the type 2 immune response and increased IL-4 and IL-13 signaling drives and perpetuates type 2 inflammation, which contributes to clinical disease features in atopic dermatitis and other type 2 inflammatory diseases3-5</li>
 <li>
 IL-4 and IL-13 are produced by various cell types such as Th2 and ILC2 cells in response to increased signaling through the IL-4Rα present on those cells6-8</li>
</ul>

<h2>Nonlesional skin is not normal skin</h2>
In atopic dermatitis, subclinical inflammation is also present in nonlesional skin1–3

About Type 2 Inflammation – Atopic Dermatitis

ATOPIC-DERMATITIS

DERMATOLOGY

<h2>Summary of Effectiveness &amp; Reduction of RSV-Hospitalization Estimates</h2>

<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td style="text-align: center;">LEGEND</td>
 </tr>
 </tbody>
</table>
Effectiveness (Case Controlled) 
 RSV-Hospitalization Reduction (compared to previous years)

<h2>Countries that have implemented nirsevimab</h2>

<h3>Implementation of&nbsp;nirsevimab&nbsp;to reach infants in US</h3>

*Can adjust administration schedules based on local epidemiology (e.g. Alaska and Hawaii) 
 **Children with chronic lung disease of prematurity who required medical support (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) any time during the 6-month period before the start of the second RSV season, Children with severe immunocompromise, Children with cystic fibrosis who have either 1) manifestations of severe lung disease (previous hospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest imaging that persist when stable) or 2) weight-for-length &lt;10th percentile, American Indian or Alaska Native children

<h4>Reference</h4>
<ol>
 <li>
 Jones JM et al, Morb Mortal Wkly Rep 2023;72:920–925. 2. Flemin-Dutra KE et al, Morb Mortal Wkly Rep 2023;72:1115-1122.</li>
</ol>

<h4>Reference</h4>
<ol>
 <li>
 Moline HL, et al. MMWR Morb Mortal Wkly Rep 2024;73:209–214.&nbsp;</li>
</ol>

<h3>Nirsevimab Receipt and Intent for Infants Survey - US</h3>
Monthly Nirsevimab Receipt and Intent Among Females Aged 18-49 Years, United States

<h4>References</h4>
<ol>
 <li>
 NIS Adult COVID Module (NIS-ACM) Hard Copy Questionnair https://www.cdc.gov/vaccines/imz-managers/nis/downloads/NIS-ACM-Questionnaire-Q1-2024-508.pdf Published Q1 2024(Accessed 05 Feb 2024)</li>
 <li>
 Nirsevimab Receipt and Intent for Infants, United States https://www.cdc.gov/vaccines/imz-managers/coverage/rsvvaxview/nirsevimab-coverage.html (Published January 10/2024 Accessed 08 Mar 2024)</li>
</ol>

<h3>Implementation of&nbsp;nirsevimab&nbsp;to reach infants in France</h3>

<h4>Parents acceptance were higher than previously estimated by French authorities</h4>

<h4>Reference</h4>
<ol>
 <li>
 DGS-URGENT N°2023_14&nbsp;<a href="https://sante.gouv.fr/IMG/pdf/dgs-urgent_2023-14_-_traitement_preventif_vrs.pdf" target="_blank">https://sante.gouv.fr/IMG/pdf/dgs-urgent_2023-14_-_traitement_preventif_vrs.pdf</a>&nbsp;(Published: 24/08/2023 Accessed 12 of March 2024)</li>
</ol>

<h3>Bronchiolitis Decline Continues; 
 Nirsevimab’s Impact Uncertain in France without specific data</h3>
Compared to previous seasons, and at this stage of the epidemic, bronchiolitis-related activities are:
&lt;3 months old: lower&nbsp;than those of the seasons before&nbsp;the emergence of Covid-19; close to or slightly lower&nbsp;than those in&nbsp;the 2021-2022 season lower&nbsp;than those in&nbsp;the 2022-2023 season.
3-11 months: 
 generally close to the activities observed during the 2021-2022 and 2022-2023 seasons (ER visits and hospitalization) lower or comparable to those in the seasons before the emergence of Covid-19, except for hospitalization rates after ER remain within the values).
Differences in terms of the impact of the bronchiolitis epidemic observed between infants &lt;3 months of age and infants 3 - 11 months&nbsp;cannot be certainly directly linked to the deployment of nirsevimab treatment on national territory,&nbsp;even if it is the youngest infants who have preferentially been able to benefit from maternity treatment.
The syndromic data of the&nbsp;Oscour network do not make it possible&nbsp;to identify infants who have been able to benefit from this preventive treatment, or to identify infants with RSV bronchiolitis.

<h4>References</h4>
<ol>
 <li>
 <a href="https://www.santepubliquefrance.fr/maladies-et-traumatismes/maladies-et-infections-respiratoires/grippe/documents/bulletin-national/infections-respiratoires-aigues-grippe-bronchiolite-covid-19-.-bulletin-du-31-janvier-2024" target="_blank">https://www.santepubliquefrance.fr/maladies-et-traumatismes/maladies-et-infections-respiratoires/grippe/documents/bulletin-national/infections-respiratoires-aigues-grippe-bronchiolite-covid-19-.-bulletin-du-31-janvier-2024</a>&nbsp;(Published 31 January 2024, Accessed in March 14th 2024)</li>
 <li>
 <a href="https://www.santepubliquefrance.fr/media/files/01-maladies-et-traumatismes/maladies-et-infections-respiratoires/infections-respiratoires-aigues/annexe_bronchio_france_1-12_mois_20240131" target="_blank">https://www.santepubliquefrance.fr/media/files/01-maladies-et-traumatismes/maladies-et-infections-respiratoires/infections-respiratoires-aigues/annexe_bronchio_france_1-12_mois_20240131</a>&nbsp;(Published 31 January 2024, Accessed in March 14th 2024)</li>
</ol>

<h3>Comparing bronchiolitis episodes before and after nirsevimab implementation (Infovac Sentinel)</h3>
RSV cases reduction observed in the target group of immunization
Over 70% of infants born since mid-Sep 2023 til 31st December have been immunized with nirsevimab

No RDT done in the first half of September

Data as of 31st of December, 2023. IRAP Network (ACTIV/AFPA)

<h3>Impact of Nirsevimab in bronchiolitis episodes (Infovac Sentinel)</h3>
Jan 2024
“The key change is the efficacy of Nirsevimab (confirmed above 80%) in France, with the very significant decrease in the number of cases before the age of 3 months.”

<h4>Reference</h4>
Infovac France Newsletter Newsletter N°10 - November 2023 | Infovac France (Published 28th of November 2023, accessed 12 of March 2024)

France

<h3>Implementation of&nbsp;nirsevimab&nbsp;to reach infants in Spain</h3>

*- Preterm infants below 35 weeks gestational age. - Infants with bronchopulmonary dysplasia64. - Infants with congenital heart disease with significant hemodynamic impairment (those being treated for congestive heart failure, those with moderate or severe pulmonary hypertension, and children with cyanotic heart disease). - Infants with severe immunosuppression due to oncohaematological processes, primary immunodeficiencies (especially combined immunodeficiencies and congenital agammaglobulinemia). ‡ Castilla y Leon:Under 7 months: From 1st March 2023;Pais Vasco: Under 3 months: From 1st July 2023,Navarra: In season

<h4>References</h4>
<ol>
 <li>
 Martinon-Torres et al. Euro Surveill 2023, 28:pii=2300606</li>
 <li>
 Calendario de inmunizaciones.&nbsp;<a href="https://vacunasaep.org/profesionales/calendario-de-inmunizaciones-aep-2024" target="_blank">https://vacunasaep.org/profesionales/calendario-de-inmunizaciones-aep-2024</a>&nbsp;published January 1st 2024, accessed 12 March 2024 43. Recomendaciones de utilización de nirsevimab&nbsp;<a href="https://www.sanidad.gob.es/areas/promocionPrevencion/vacunaciones/comoTrabajamos/docs/Nirsevimab.pdf" target="_blank">https://www.sanidad.gob.es/areas/promocionPrevencion/vacunaciones/comoTrabajamos/docs/Nirsevimab.pdf</a>, published July 2023,accessed 12 of March 2024</li>
</ol>

<h3>The deployment of Nirsevimab capitalized on existent immunization frameworks, facilitating its assimilation into routine vaccine administration practices.</h3>
1. Burden of Disease 
 Evidence of RSV burden in all infants and surveillance generated1,5
2. Regulatory &amp; scientific societies endorsement 
 EMA approved2&nbsp;and pediatric society (AEP)3recommended nirsevimab for prevention of RSV in all infants during their first RSV season
3. NIP inclusion 
 As for any vaccine-like product, a NITAG4&nbsp;multidisciplinary working group evaluated and recommended nirsevimab based on :
<ul>
 <li>Scientific</li>
 <li>Epidemiological</li>
 <li>Ethical</li>
 <li>Political</li>
 <li>Economical</li>
</ul>

<h4>Abbreviations</h4>
AEP: Spanish Academy of Pediatrics,&nbsp;EMA: European Medicines Agency ,&nbsp;NIP: National Immunization Program

<h4>References</h4>
<ol>
 <li>
 Wildenbeest JG et al. Lancet Respir Med. 2023 Apr;11(4):341-353. doi: 10.1016/S2213-2600(22)00414-3. Epub 2022 Nov 10.</li>
 <li>
 EMA New medicine to protect babies and infants from respiratory syncytial virus (RSV) infection&nbsp;<a href="https://www.ema.europa.eu/en/news/new-medicine-protect-babies-and-infants-respiratory-syncytial-virus-rsv-infection" target="_blank">https://www.ema.europa.eu/en/news/new-medicine-protect-babies-and-infants-respiratory-syncytial-virus-rsv-infection</a>&nbsp;published 16 September 2022, accesse 12 of March 2024</li>
 <li>
 Calendario de inmunizaciones.&nbsp;<a href="https://vacunasaep.org/profesionales/calendario-de-inmunizaciones-aep-2024" target="_blank">https://vacunasaep.org/profesionales/calendario-de-inmunizaciones-aep-2024</a>&nbsp;published January 1st 2024, accessed 12 March 2024</li>
 <li>
 Recomendaciones de utilización de nirsevimab&nbsp;<a href="https://www.sanidad.gob.es/areas/promocionPrevencion/vacunaciones/comoTrabajamos/docs/Nirsevimab.pdf" target="_blank">https://www.sanidad.gob.es/areas/promocionPrevencion/vacunaciones/comoTrabajamos/docs/Nirsevimab.pdf</a>, published July 2023. accessed 12 of March 2024</li>
 <li>
 Martinón-Torres, Fet al. BMC Infect Dis&nbsp;23, 385 (2023).&nbsp;</li>
</ol>

<h3>Successful implementation demonstrated by high coverage</h3>
Galicia, Spain is conducting an impact study on nirsevimab and RSV
<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td>Group</td>
 <td>Number of Immunized 
 (as of Feb 25th, 2024)</td>
 <td>% Coverage Rate</td>
 </tr>
 <tr>
 <td>At birth</td>
 <td style="text-align: center;">5,638</td>
 <td style="text-align: center;">92.7%</td>
 </tr>
 <tr>
 <td>Catch-up</td>
 <td style="text-align: center;">6,234</td>
 <td style="text-align: center;">85.3%</td>
 </tr>
 <tr>
 <td>Increased Risk</td>
 <td style="text-align: center;">349</td>
 <td style="text-align: center;">100%</td>
 </tr>
 <tr>
 <td>Total</td>
 <td style="text-align: center;">12,221</td>
 <td>&nbsp;</td>
 </tr>
 </tbody>
</table>

<h4>References</h4>
<ol>
 <li>
 Martinon-Torres et al. ESWI Respiratory Virus Summit 2024 | ESWI 5th of March 2024 Brussels &amp; online</li>
</ol>

<h3>Impact of Nirsevimab implementation in Galicia</h3>

Cumulative weekly RSV hospitalization rate in Galicia by season, up to Feb 4th 2024 (week 5/24)

<h4>References</h4>
<ol>
 <li>
 Results of implementation of Nirsevimab in Galicia Nirsegal.com published February 2024 accessed march 2024</li>
 <li>
 Martinon-Torres et al. ESWI Respiratory Virus Summit 2024 | ESWI 5th of March 2024 Brussels &amp; online</li>
</ol>

<h3>Cumulative cases in other age groups not lower than previous seasons in children 1 to 4 years old and older than 60 years, not targeted for nirsevimab immunization</h3>

Higher cumulative case number than median of previous seasons
Weekly RSV hospitalization rate in Galicia by season, week 8 2024

<h4>Reference</h4>
<ol>
 <li>
 Results of implementation of Nirsevimab in Galicia Nirsegal.com published February 2024 accessed March 2024 2. Martinon-Torres et al. ESWI Respiratory Virus Summit 2024 | ESWI 5th of March 2024 Brussels &amp; online</li>
</ol>

<h3>Effectiveness of Nirsevimab Against RSV-Related Outcomes in Hospital and Primary Care Settings</h3>
A Retrospective Cohort Study in Infants in Catalonia (Spain)
<table border="1" cellpadding="1" cellspacing="1" style="width:100%;">
 <tbody>
 <tr>
 <td>Outcome</td>
 <td style="width: 9%;">N</td>
 <td>Rate per 100,000 person days</td>
 <td style="width: 9%;">N</td>
 <td>Rate per 100,00 person days</td>
 <td>Adjusted hazard ratio (95% CI)</td>
 <td>Effectiveness</td>
 </tr>
 <tr>
 <td>ICU admission</td>
 <td style="text-align: center; width: 9%;">17</td>
 <td style="text-align: center;">2.13</td>
 <td style="text-align: center; width: 9%;">8</td>
 <td style="text-align: center;">0.33</td>
 <td style="text-align: center;">0.099 (0.041 to 0.237)</td>
 <td style="text-align: center;">90.1% (76.3% to 95.9%)</td>
 </tr>
 <tr>
 <td>Hospital admission</td>
 <td style="text-align: center; width: 9%;">76</td>
 <td style="text-align: center;">9.55</td>
 <td style="text-align: center; width: 9%;">52</td>
 <td style="text-align: center;">2.16</td>
 <td style="text-align: center;">0.124 (0.086 to 0.179)</td>
 <td style="text-align: center;">87.6% (82.1% to 91.4%)</td>
 </tr>
 <tr>
 <td>Viral pneumonia</td>
 <td style="text-align: center; width: 9%;">14</td>
 <td style="text-align: center;">2.06</td>
 <td style="text-align: center; width: 9%;">42</td>
 <td style="text-align: center;">1.79</td>
 <td style="text-align: center;">0.393 (0.203 to 0.758)</td>
 <td style="text-align: center;">60.7% (24.2% to 79.7%)</td>
 </tr>
 <tr>
 <td>Hospital emergency visits</td>
 <td style="text-align: center; width: 9%;">354</td>
 <td style="text-align: center;">45.1</td>
 <td style="text-align: center; width: 9%;">604</td>
 <td style="text-align: center;">25.5</td>
 <td style="text-align: center;">0.446 (0.385 to 0.516)</td>
 <td style="text-align: center;">55.4% (48.4% to 61.5%)</td>
 </tr>
 <tr>
 <td>Primary care attended bronchiolitis</td>
 <td style="text-align: center; width: 9%;">617</td>
 <td style="text-align: center;">93.9</td>
 <td style="text-align: center; width: 9%;">1,560</td>
 <td style="text-align: center;">69.7</td>
 <td style="text-align: center;">0.519 (0.467 to 0.576)</td>
 <td style="text-align: center;">48.1% (42.4% to 53.3%)</td>
 </tr>
 <tr>
 <td>RSV infection</td>
 <td style="text-align: center; width: 9%;">31</td>
 <td style="text-align: center;">4.57</td>
 <td style="text-align: center; width: 9%;">71</td>
 <td style="text-align: center;">3.04</td>
 <td style="text-align: center;">0.311 (0.200 to 0.483)</td>
 <td style="text-align: center;">68.9% (51.7% to 80.0%)</td>
 </tr>
 </tbody>
</table>

Findings: Among 26,525 infants, a dose of nirsevimab led to an adjusted HR for hospital admission due to RSV bronchiolitis of 0·124 (0·086 to 0·179) and an adjusted HR for ICU admission of 0·099 (0·041 to 0·237). Additionally, the adjusted HR observed for emergency visits was 0·446 (95% CI: 0·385 to 0·516), 0·393 (95% CI: 0·203 to 0·758) for viral pneumonia, 0·519 (95% CI: 0·467 to 0·576) for bronchiolitis attended in primary care, and 0·311 (95% CI: 0·200 to 0·483) for RSV infection. Sensitivity and negative control outcome analyses supported these findings.

<h4>Reference</h4>
<ol>
 <li>
 Coma E. et al, Preprints with the Lancet, available at SSRN:&nbsp;<a href="https://ssrn.com/abstract=4749763" target="_blank">https://ssrn.com/abstract=4749763</a></li>
</ol>

Spain

<h3>Implementation of&nbsp;nirsevimab&nbsp;to reach infants in Luxembourg</h3>

<h4>Reference</h4>
Recommandations du Conseil supérieur des maladies infectieuses concernant l’immunisation passive contre le RSV par des nouveaux anticorps CONSEIL SUPERIEUR D’HYGIENE (public.lu) published July 2023; accessed 14th of March 2024

<h3>Luxembourg</h3>
<ul>
 <li>The&nbsp;length of hospital stay&nbsp;was significantly&nbsp;reduced&nbsp;from a mean&nbsp;of 5.1 days&nbsp;(SD: 5.4) in 2022 compared to&nbsp;3.2 days&nbsp;(SD: 2.5) in 2023 (p &lt; 0.001).</li>
 <li>Infants &lt; 6 months old (5.6&nbsp;days in 2022 vs&nbsp;3.4&nbsp;days in 2023, p &lt; 0.001)</li>
 <li>78.5%&nbsp;(22/28) of infants up to 6 months of age needing oxygen supplementation were not immunised.</li>
 <li>69.2%&nbsp;(9/13) received Nasal high flow therapy were not immunized.</li>
 <li>66.6%&nbsp;(6/9) admitted to PICU were not immunized.</li>
</ul>

The majority of severe RSV LRTI cases were on non-immunized infants
<ul>
 <li>Coverage in Maternity wards October to mid-December 2023 was estimated at 84% (from 66% to 94%).</li>
 <li>A decrease of 69% RSV lab-confirmed hospitalizations among infants under 6 months old.</li>
 <li>With a 38% decrease in children under 5 years of age 65.3% of infants under 6 months were not immunized.</li>
</ul>

<h4>Reference</h4>
Ernst C et al. Euro Surveill.&nbsp;2024;29(4):pii=2400033.

Luxembourg

RESPIRATORY-SYNCYTIAL-VIRUS

VACCINES

Real World Evidence Impact of universal immunization with Nirsevimab

<h2>By the time pompe disease slows them down, the damage has already begun2–4</h2>
Diagnose and manage Pompe disease early to help your patients stay ahead of their disease2–4
<h3>Pompe disease is a life-threatening, progressive neuromuscular disorder that causes irreversible muscle damage1–4</h3>
Pompe disease, also referred to as acid maltase deficiency or glycogen storage disease type II (GSDII), is an underrecognized, inherited multisystemic disorder that causes progressive muscle damage, profound disability and premature death.1,4,5 
 For patients, Pompe disease means progressive respiratory and muscle complications, as well as life-limiting burden.4
Pompe disease is heterogeneous, with varying ages of onset and rates of progression4,6

<div>
 <table border="1" cellpadding="10" cellspacing="1">
 <tbody>
 <tr>
 <td style="background-color: rgb(244, 242, 246);">IOPD</td>
 <td style="background-color: rgb(244, 242, 246);">&nbsp;</td>
 <td style="background-color: rgb(244, 242, 246);">LOPD</td>
 </tr>
 <tr>
 <td>Infantile-onset Pompe disease&nbsp;1 in 138,000 people7*</td>
 <td>Prevalence 1 in 40,000 
 for all forms 
 of Pompe disease1†</td>
 <td>Late-onset Pompe disease&nbsp;1 in 57,000 people7*</td>
 </tr>
 <tr>
 <td>Within the first year of life5</td>
 <td>Presentation</td>
 <td>At any point during childhood or adulthood5</td>
 </tr>
 <tr>
 <td>Rapidly progressive and, if left unmanaged, results in death by 2 years of age, most commonly due to cardiorespiratory failure3</td>
 <td>Progression</td>
 <td>Steadily progressive and can result in premature death, most commonly due to respiratory failure5</td>
 </tr>
 </tbody>
 </table>
</div>

<h2>Diagnose and manage Pompe disease early to help reduce patient burden4,6,8</h2>
*Estimates based on studies from The Netherlands. No prevalence studies have been performed in Canada. †Based on one study in a New York population.

Pathophysiology behind the Burden of Disease
Pompe disease is caused by a deficiency of acid α-glucosidase (GAA) enzyme activity, resulting in uncontrolled and progressive lysosomal glycogen accumulation in muscle cells throughout the body1,3,4
<ul>
 <li>In patients that present with Pompe disease before 1 year of age (infantile-onset), GAA enzyme activity may be completely missing; and if some activity remains, it is usually &lt;1% of normal5</li>
</ul>

Uncontrolled glycogen accumulation causes lysosomes to swell and rupture, resulting in1
<ul>
 <li>Irreversible cellular damage6,10</li>
 <li>Progressive destruction of skeletal muscle (including respiratory musculature), cardiac muscle and smooth muscle9,10</li>
 <li>Debilitating respiratory, motor, musculoskeletal, cardiac, bulbar, and gastrointestinal (GI) muscular manifestations3,9,13–15</li>
</ul>

<h2>Diagnostic and treatment delays result in unchecked disease progression leading to respiratory complications, muscle damage, life-altering burden and/or death2,16</h2>
<h3>Patients with Pompe Disease often Face Delayed Diagnosis1</h3>
<ul>
 <li>
 Delayed diagnosis can lead to significant muscle tissue deterioration, diminished physical function and premature death2,17</li>
 <li>The median delay to definitive diagnosis for patients with LOPD can be as much as 7 years18,19</li>
</ul>

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