Drug Trials Snapshots: LAMZEDE
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the LAMZEDE Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
LAMZEDE (velmanase alfa-tycv)
lam zeed'
Chiesi USA, Inc.
Original Approval date: February 16, 2023
DRUG TRIALS SNAPSHOT SUMMARY
What is the drug for?
LAMZEDE is an enzyme replacement therapy that is used for the treatment of adult and pediatric patients with alpha-mannosidosis.
Alpha-mannosidosis is a rare disease where patients have decreased activity of the enzyme alpha-mannosidase, which breaks down mannose containing oligosaccharides (a complex sugar). Oligosaccharides can build up in organs and tissues causing a weakened immune system, frequent lung infections, skeletal abnormalities, and muscle weakness.
How is this drug used?
LAMZEDE is administered by a healthcare provider using a needle placed in a vein (known as intravenous infusion) once every week.
Who participated in the clinical trials?
The FDA approved LAMZEDE based primarily on evidence from one clinical trial (Trial 1) of 25 patients with alpha-mannosidosis. The trial was conducted at seven sites in Europe.
All 25 patients were evaluated for efficacy and side effects.
How were the trials designed?
LAMZEDE was evaluated in one clinical trial of 25 patients with alpha-mannosidosis.
The benefit and side effects of LAMZEDE were evaluated primarily in one clinical trial. Trial 1 enrolled children and adults with alpha-mannosidosis who had a genetic and corresponding enzyme deficiency. The enzyme deficiency was determined to be a good target for therapy with LAMZEDE based on laboratory data. The clinical trial compared patients who received LAMZEDE (the missing enzyme) with patients who never received treatment to replace the missing enzyme. Patients were randomized to receive LAMZEDE or placebo every week for 12 months. Neither the patients nor the healthcare providers knew which treatment was given until after the trial was completed.
The benefit of LAMZEDE was assessed after 12 months of treatment by assessing 3-minute stair climbing test (3MSCT), 6-minute walking test (6MWT), forced vital capacity (FVC), and serum oligosaccharides at 12 months. Patients treated with LAMZEDE experienced a larger average increase in steps on the 3MSCT, a larger average distance in the 6MWT, and larger increase in FVC after 12 months of treatment, compared to patients who received placebo for 12 months. Patients treated with LAMZEDE also experienced a larger average decline in serum oligosaccharides after 12 months of treatment.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many males and females were enrolled in the clinical trial used to evaluate the efficacy of LAMZEDE.
Figure 1. Baseline Demographics by Sex
Source: Adapted from FDA Review
Figure 2 summarizes how many patients by race were enrolled in the clinical trial used to evaluate the efficacy of LAMZEDE.
Figure 2. Baseline Demographics by Race
Source: Adapted from FDA Review
Figure 3 summarizes how many patients by age were enrolled in the clinical trial used to evaluate the efficacy of LAMZEDE.
Figure 3. Baseline Demographics by Age
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Demographics Table
| Demographic | LAMZEDE N=15 |
Placebo N=10 |
Total N=25 |
| Sex, n (%) | |||
| Male | 9 (60) | 5 (50) | 14 (56) |
| Female | 6 (40) | 5 (50) | 11 (44) |
| Age, years | |||
| Mean (SD) | 18.5 (9.0) | 19.7 (8.9) | 19.0 (8.8) |
| Median (min, max) | 20 (6, 35) | 18.5 (6, 35) | 20 (6, 35) |
| Age group, years, n (%) | |||
| ≥6 to <18 | 7 (47) | 5 (50) | 12 (48) |
| ≥18 to ≤35 | 8 (53) | 5 (50) | 13 (52) |
| Race, n (%) | |||
| White | 15 (100) | 10 (100) | 25 (100) |
| Country of participation, n (%) | |||
| United States | 0 (0) | 0 (0) | 0 (0) |
| United Kingdom | 0 (0) | 1 (10) | 1 (4) |
| Poland | 3 (20) | 0 (0) | 3 (12) |
| Spain | 2 (13) | 1 (10) | 3 (12) |
| Germany | 4 (27) | 1 (10) | 5 (20) |
| France | 4 (27) | 2 (20) | 6 (24) |
| Other | 2 (13) | 5 (50) | 7 (28) |
Source: Adapted from FDA Review
Abbreviations: SD, standard deviation
What are the benefits of this drug?
LAMZEDE improved walkable distance, ability to climb stairs, and lung function in children and adults with alpha-mannosidosis. LAMZEDE also reduced blood levels of oligosaccharides (a complex sugar which is abnormally high in patients with alpha-mannosidosis) in both children and adults with alpha-mannosidosis.
What are the benefits of this drug (results of trials used to assess efficacy)?
Table 2. Change From Baseline in Clinical Endpoints and Serum Oligosaccharide in LAMZEDE- or Placebo-Treated Patients With Alpha-Mannosidosis Over 12 Months
| Endpoint | LAMZEDE N=15 |
Placebo N=10 |
Treatment Difference (95% CI) |
| 3MSCT (steps/min) | |||
| Baseline mean (SD) | 52.9 (11.2) | 55.5 (16.0) | NA |
| Mean absolute change from baseline (SD) | 0.6 (8.6) | -2.4 (5.5) | 2.6 (-3.8, 9.1) |
| Mean relative change (%) from baseline (SD) | 0.5 (16.1) | -3.6 (13.1) | 3.4 (-9.5, 16.3) |
| FVC (% predicted) | |||
| Baseline mean (SD) | 81.7 (20.7) | 90.4 (10.4) | NA |
| Mean absolute change from baseline (SD) | 8.2 (9.9) | 2.0 (12.6) | 5.5 (-5.0, 16.1) |
| Mean relative change (%) from baseline (SD) | 11.4 (13.1) | 1.9 (15.4) | 7.4 (-5.7, 20.5) |
| 6MWT (meters) | |||
| Baseline mean (SD) | 459.6 (72.3) | 465.7 (140.5) | NA |
| Mean absolute change from baseline (SD) | 4.4 (46.1) | -4.6 (40.8) | 7.4 (-30.7, 45.5) |
| Mean relative change (%) from baseline (SD) | 1.2 (9.8) | -0.8 (10.8) | 1.6 (-7.2, 10.4) |
| Serum oligosaccharides (umol/L) | |||
| Baseline mean (SD) | 6.8 (1.2) | 6.6 (1.9) | NA |
| Mean absolute change from baseline (SD) | -5.1 (1.2) | -1.6 (1.7) | -3.5 (-4.4, -2.6) |
| Mean relative change (%) from baseline (SD) | -75.8 (11.2) | -20.3 (24.0) | -55.6 (-69.3, -41.9) |
Source: LAMZEDE Prescribing Information
For each endpoint, the treatment difference in the adjusted means (95% CI) was calculated using an analysis of covariance that included baseline age, baseline value of the endpoint as covariates. Missing data of FVC (% predicted) were not imputed.
Abbreviations: 3MSCT, 3-minute climbing stair test; 6MWT, 6-minute walking test; CI, confidence interval; FVC, forced vital capacity; NA, not applicable; SD, standard deviation
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
The pivotal trial enrolled only White patients and patients younger than 65 years of age. Only subgroup analyses by sex can be conducted. However, the trial population was too small to enable interpretation of these subgroup analyses .
- Sex: In this small trial size, a difference in how well the drug worked between male and females could not be determined because of limitations of the small sample size.
- Race: All trial participants were White; therefore, differences in how LAMZEDE worked among races could not be determined.
- Age: The difference how well the drug worked between pediatric than adult patients could not be determined.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Change From Baseline in Clinical Endpoints and Serum Oligosaccharide in LAMZEDE- or Placebo-Treated Male Patients With Alpha-Mannosidosis Over 12 Months
| Endpoint - Males | LAMZEDE N=9 |
Placebo N=5 |
Treatment Difference (95% CI) |
| 3MSCT (steps/min) | |||
| Baseline mean (SD) | 56.3 (12.8) | 57.6 (17.5) | NA |
| Mean absolute change from baseline (SE) | 0.7 (8.5) | -3.1 (4.5) | 3.6 (-6.4, 13.7) |
| Mean relative change (%) from baseline (SE) | 1.0 (14.8) | -5.9 (9.8) | 6.6 (-11.3, 24.5) |
| FVC (% predicted) | |||
| Baseline mean (SD) | 86.7 (23.0) | 95.0 (10.2) | NA |
| Mean absolute change from baseline (SE) | 8.9 (5.9) | 3.5 (2.7) | 4.1 (-4.5, 12.7) |
| Mean relative change (%) from baseline (SE) | 11.4 (9.1) | 3.6 (2.8) | 5.1 (-6.3, 16.4) |
| 6MWT (meters) | |||
| Baseline mean (SD) | 491.4 (72.2) | 464.0 (192.1) | NA |
| Mean absolute change from baseline (SE) | -1.7 (53.3) | -6.2 (33.4) | 1.3 (-59.9, 62.5) |
| Mean relative change (%) from baseline (SE) | -0.6 (9.9) | -2.1 (10.0) | 0.3 (-11.5, 12.1) |
| Serum oligosaccharides (µmol/L) | |||
| Baseline mean (SD) | 6.6 (1.3) | 6.1 (1.5) | NA |
| Mean absolute change from baseline (SE) | -5.2 (1.5) | -1.0 (1.8) | -3.8 (-5.4, -2.3) |
| Mean relative change (%) from baseline (SE) | -78.0 (11.3) | -14.3 (28.7) | -62.6 (-87.3, -37.9) |
Source: Adapted from FDA Review
For each endpoint, the treatment difference in the adjusted means (95% CI) was calculated using an analysis of covariance that included baseline age, baseline value of the endpoint as covariates. Missing data of FVC (% predicted) were not imputed.
Abbreviations: 3MSCT, 3-minute climbing stair test; 6MWT, 6-minute walking test; CI, confidence interval; FVC, forced vital capacity; NA, not applicable; SD, standard deviation
Table 4. Change From Baseline in Clinical Endpoints and Serum Oligosaccharide in LAMZEDE- or Placebo-Treated Female Patients With Alpha-Mannosidosis Over 12 Months
| Endpoint - Females | LAMZEDE N=6 |
Placebo N=5 |
Treatment Difference (95% CI) |
| 3MSCT (steps/min) | |||
| Baseline mean (SD) | 47.9 (6.2) | 53.4 (16.1) | NA |
| Mean absolute change from baseline (SE) | 0.5 (9.4) | -1.7 (6.7) | 0.3 (-11.4, 11.9) |
| Mean relative change (%) from baseline (SE) | -0.2 (19.4) | -1.4 (16.7) | -3.2 (-29.7, 23.2) |
| FVC (% predicted) | |||
| Baseline mean (SD) | 74.6 (16.6) | 86.8 (10.0) | NA |
| Mean absolute change from baseline (SE) | 7.2 (14.6) | 0.8 (17.6) | 16.8 (-15.1, 48.6) |
| Mean relative change (%) from baseline (SE) | 11.4 (18.7) | 0.5 (21.5) | 21.6 (-17.4, 60.6) |
| 6MWT (meters) | |||
| Baseline mean (SD) | 411.8 (41.6) | 467.4 (86.6) | NA |
| Mean absolute change from baseline (SE) | 13.5 (35.2) | -3.0 (51.2) | 4.3 (-62.1, 70.6) |
| Mean relative change (%) from baseline (SE) | 3.9 (9.8) | 0.5 (12.5) | -2.9 (-18.4, 12.5) |
| Serum oligosaccharides (µmol/L) | |||
| Baseline mean (SD) | 7.0 (1.0) | 7.1 (2.2) | NA |
| Mean absolute change from baseline (SE) | -5.0 (0.8) | -2.1 (1.6) | -3.0 (-4.0, -2.0) |
| Mean relative change (%) from baseline (SE) | -72.5 (11.3) | -26.3 (19.5) | -47.2 (-65.2, -29.2) |
Source: Adapted from FDA Review
For each endpoint, the treatment difference in the adjusted means (95% CI) was calculated using an analysis of covariance that included baseline age, baseline value of the endpoint as covariates. Missing data of FVC (% predicted) were not imputed.
Abbreviations: 3MSCT, 3-minute climbing stair test; 6MWT, 6-minute walking test; CI, confidence interval; FVC, forced vital capacity; NA, not applicable; SD, standard deviation
What are the possible side effects?
LAMZEDE may cause serious side effects such as hypersensitivity reactions and infusion associated reactions.
The most common side effects are nasal and throat irritation (nasopharyngitis), fever (pyrexia), headache, and joint pain (arthralgia).
What are the possible side effects (results of trials used to assess safety)?
Table 5 summarizes adverse reactions in patients with alpha-mannosidosis who were treated with LAMZEDE or were not treated with LAMZEDE for 12 months.
Table 5. Adverse Reactions (≥2 Patients) in Adult and Pediatric Patients With Alpha-Mannosidosis Treated With LAMZEDE in Trial 1
| Adverse Reaction | LAMZEDE N=15 n (%) |
Placebo N=10 n (%) |
| Nasopharyngitis | 10 (66) | 7 (70) |
| Pyrexia | 6 (40) | 5 (50) |
| Headache | 5 (33) | 3 (30) |
| Arthralgia | 3 (20) | 1 (10) |
| Acute tonsillitis | 2 (13) | 0 |
| Urinary tract infection | 2 (13) | 1 (10) |
| Eye pruritus | 2 (13) | 0 |
| Gastroenteritis | 2 (13) | 0 |
| Hypersensitivity | 2 (13) | 0 |
| Influenza | 2 (13) | 0 |
| Syncope | 2 (13) | 0 |
| Toothache | 2 (13) | 0 |
| Back pain | 2 (13) | 1 (10) |
| Ear infection | 2 (13) | 1 (10) |
Source: LAMZEDE Prescribing Information
1 Urinary tract infection is composed of similar terms
Were there any differences in side effects among sex, race, and age?
- Sex: In this small trial size, a difference in side effects between male and females could not be determined because of limitations of the small sample size.
- Race: All trial participants were White; therefore, differences in how LAMZEDE worked among races could not be determined.
- Age: The occurrence of side effects, specifically hypersensitivity reactions, was higher in pediatric than adult patients. No patients over 65 years old were included in the trial.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.