Lumizyme is approved for the long-term treatment of adult and pediatric late-onset Pompe disease (LOPD)1
Lumizyme helped maintain stabilization of pulmonary function and improvements in walking distance for up to 104 weeks.2
Overview of the LOTS and LOTS extension studies
The LOTS and LOTS extension study were the first pivotal, large-scale studies to demonstrate the efficacy of Lumizyme in pediatric and adult populations.3-6
Study design overview1,2,7
LOTS |
LOTS Extensiona | |
| Study Design | Randomized, double-blind, placebo-controlled, multicenter trial (N=90: 45 males, 45 females) | Open-label extension study of patients who completed LOTS on active therapy (N=55) |
| Objective | Establish the safety and efficacy of Lumizyme in patients with LOPD | Determine the durability of the efficacy and safety of Lumizyme initially observed in LOTS |
| Dosing and duration | Patients were randomized 2:1 to Lumizyme 20 mg/kg or placebo EOW for 78 weeks | After the 78-week administration of Lumizyme in LOTS, administration continued through week 104 |
| Median age at diagnosis |
Patients were:
| Patients entering extension had completed LOTS on active therapy |
aThe extension study was not designed to evaluate the treatment effect of Lumizyme in the small number of patients who crossed over from the placebo group to active therapy for a relatively short period of time.
EOW=every other week; ERT=enzyme-replacement therapy; FVC=forced vital capacity.
Lumizyme stabilized pulmonary function, which was maintained for up to 104 weeks1,2,8
Mean change from baseline in predicted FVC (%)
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LOTS
In LOTS, after 78 weeks, patients taking Lumizyme experienced a significant treatment effect in FVC vs placebo.1,8
The percentage of predicted FVC increased by a mean of 1.2% vs a mean decrease of 2.2% in the placebo group, indicating a treatment effect of 3.4% (95% CI, 1.3-5.5; p=0.004 vs placebo).
LOTS extension
In the LOTS extension, patients taking Lumizyme maintained the positive effects observed in pulmonary function over 104 weeks of therapy.2
For the Lumizyme group (n=53), there was a mean change of 0.8% ± 6.7% (95% CI, -1.1-2.6) in the percentage of predicted FVC from LOTS baseline to week 104.
Changes observed in LOTS in percentage of predicted FVC from baseline to week 78. Patients who continued on Lumizyme (n=55)b maintained stabilization of pulmonary function for up to 104 weeks.2,8
ANCOVA=analysis of covariance.
aANCOVA estimate of mean.
bA total of 55 patients enrolled in the LOTS extension study; however, only 54 had baseline assessments and 53 had data available at week 104.
Lumizyme maintained improvements in walking distance for up to 104 weeks1,2,8
Mean change from baseline in Six-Minute Walk Test (6MWT) distance (meters)
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LOTS
In LOTS, after 78 weeks, patients taking Lumizyme had increased distance walked in the 6MWT.1,8
In the 6MWT, the mean change from baseline in distance walked in the Lumizyme group was 25 meters vs a mean decrease of 3 meters in the placebo group, indicating a treatment effect of 28 meters (95% CI, -1 to 52; p=0.03 vs placebo).1,8
LOTS extension
In the LOTS extension, patients taking Lumizyme maintained the positive effects observed in walking distance over 104 weeks of therapy.2
In the 6MWT, patients remaining on Lumizyme (n=53) had a mean (± SD) increase of 21.3 ± 78.0 meters in walking distance (95% CI, -0.2 to 42.8) from LOTS baseline to week 104.2
Changes observed in LOTS in distance walked from baseline to week 78. Patients who continued on Lumizyme (n=55)b maintained stabilization of pulmonary function for up to 104 weeks.2,8
6MWT=six-minute walk test.
aANCOVA estimate of mean.
bA total of 55 patients enrolled in the LOTS extension study; however, only 54 had baseline assessments and 53 had data available at week 104.
Adverse reactions reported in LOTS clinical trial
The LOTS clinical trial reported serious adverse reactions in patients treated with Lumizyme—including anaphylaxis, which presented as angioedema, throat tightness, and chest pain/discomfort.1,2 One patient with a history of Wolff-Parkinson-White syndrome experienced a serious adverse reaction of supraventricular tachycardia.1
Adverse reactions occurring in at least 3% of Lumizyme-treated LOPD patients with a higher incidence than in the placebo-treated patients1
Adverse Reaction |
Alglucosidase Alfa |
Placebo |
| Hyperhidrosis | 5 (8.3) | 0 (0) |
| Urticaria | 5 (8.3) | 0 (0) |
| Anaphylaxis | 4 (6.7) | 0 (0) |
| Chest discomfort | 4 (6.7) | 1 (3.3) |
| Muscle twitching | 4 (6.7) | 1 (3.3) |
| Myalgia | 3 (5.0) | 1 (3.3) |
| Flushing/feeling hot | 3 (5.0) | 0 (0) |
| Increased blood pressure | 3 (5.0) | 0 (0) |
| Vomiting | 3 (5.0) | 0 (0) |
| Peripheral edema | 2 (3.3) | 0 (0) |
| Pruritus | 2 (3.3) | 0 (0) |
| Papular rash | 2 (3.3) | 0 (0) |
| Throat tightness | 2 (3.3) | 0 (0) |
Adverse events (AEs) reported in the LOTS extension clinical trial2
- The most frequently reported AEs by percentage of patients affected were falls (65%), headache (52%), and nasopharyngitis (48%); every patient reported at least 1 AE
- Treatment-related AEs were mainly infusion-associated reactions (IARs) observed in 35% of patients that were generally mild to moderate in severity
- The most frequent IARs occurring in at least 10% of patients were nausea, headache, and urticaria
- Twenty-five percent of the patients reported serious adverse events; the majority were unrelated to study drug, as assessed by the investigators
- No deaths or anaphylactic reactions were observed during the extension study
Thirty patients from LOTS and LOTS extension were followed for 10 years9
Study design overview9
| Study Design | Prospective, open-label, multicenter cohort study (N=30) Clinical assessments took place every 3-6 months before and after the start of Lumizyme |
| Objective | Determine the effects of 10 years of Lumizyme in adult patients with Pompe disease, focusing on individual variability in treatment response |
| Dosing and duration | 20 mg/kg EOW for 10 years (unless patients experienced unmanageable adverse reactions or decided to stop treatment) |
| At baseline | Patients completed LOTS and LOTS extension on active therapy |
| Study limitations |
Conclusion should be interpreted with caution because of the limited number of patients across subgroups, plus the fact that they all had some level of disease severity to be included in the initial trial (LOTS) This relatively severe involvement is probably most clearly reflected by the fact that patients’ median supine FVC at start of Lumizyme was only 33% of their predicted normal value, already on the edge of ventilator dependency |
Patients treated with Lumizyme experienced a period of stabilization in upright FVC followed by a slow decline9
In the 10-year study, patients taking Lumizyme experienced an FVC upright stabilization followed by a decline9
- The percentage of predicted FVC upright was relatively stable over the first 5 years, followed by a decline9
- At 10 years, the percent of predicted FVC upright decreased by 119
Patients treated with Lumizyme experienced improvements in walking distance for a period, followed by a decline9
In the 10-year study, patients taking Lumizyme had increased distance walked in the 6MWT for a period, followed by a decline9
- In the 6MWT, patients experienced improvements during the first 3 years of treatment, followed by a decline9
- At 10 years, the average percentage of predicted 6MWT decreased by 22.29
M=meters
aOne patient received Lumizyme for 1 month only due to severe infusion-associated reactions and was thus excluded from analysis. Data from twenty-nine patients were analyzed.
Over 10 years, initial positive response to Lumizyme is followed by a slow decline9
Combined individual patients’ response on 6MWT and upright FVC
Initial response is approximately the first 3 to 5 years of treatment. Secondary response follows that initial response until conclusion of study.
Predicting when a patient might begin to decline is difficult9
Some patients taking Lumizyme experienced benefit for up to 7-8 years. Others began to decline after 1-2 years. Sex, disease duration, and baseline disease severity did not significantly alter disease course.9
76% (22/29) of patients experienced a decline in at least 1 outcome during the secondary response period.9
Safety information reported in the 10-year study9
Lumizyme was discontinued in 2 patients (at 1 and 33 months after the start of treatment respectively) for severe infusion-associated reactions and/or very high antibody titers affecting treatment efficacy. After treatment was stopped, their clinical condition slowly worsened.
LOPD=late-onset Pompe disease.
Indication
Reference: 1. Lumizyme (alglucosidase alfa). Prescribing information. Genzyme Corporation, Cambridge, MA. 2. van der Ploeg AT et al. Mol Genet Metab. 2012;107(3):456-461. 3. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT00158600 Updated April 28, 2015. Accessed April 29, 2025. 4. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT01942590 Updated July 2, 2019. Accessed April 29, 2025. 5. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT01924845 Updated June 14, 2018. Accessed April 29, 2025. 6. ClinicalTrials. gov website. https://clinicaltrials.gov/ct2/show/NCT00077662 Updated May 5, 2015. Accessed April 29, 2025. 7. Reuser AJ et al. Exp Cell Res. 1984;155(1):178-189. 8. van der Ploeg AT et al. N Engl J Med. 2010;362(15):1396-1406. 9. Harlaar L et al. Neurology. 2019;93(19):e1756-e1767.
