1-year pivotal trial | Lamzede® (velmanase alfa-tycv)

Demonstrated favorable results in both pharmacodynamic and functional measures¹

When it comes to efficacy, Lamzede has favorable results in several important disease categories.¹

Trial 1 (rhLAMAN-05) results show the benefit of Lamzede for patients with alpha-mannosidosis, especially over time and in pediatric patients²

Studied in an even distribution of pediatric and adult patients¹

Patients were 6-17 years old (pediatric) and 18-35 years old (adult), with confirmed diagnosis of alpha-mannosidosis.

See eligibility
criteria

Lamzede achieved significant pharmacodynamic response¹

Patients receiving Lamzede showed a favorable response in both pharmacodynamic and functional measures.

View co-primary
endpoints

Favorable results in prioritized secondary endpoints¹

Patients receiving Lamzede showed favorable results in endurance walking and pulmonary function.

View prioritized
secondary endpoints

Study design

Trial 1 (rhLAMAN-05) was a Phase III, international, multicenter, double-blind, randomized, placebo-controlled parallel-group trial which assessed Lamzede in patients with alpha-mannosidosis.²

Efficacy and safety assessed in 25 patients with this ultra-rare disease.²

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Eligibility criteria included confirmed α-mannosidase activity and no history of bone marrow transplantation²

Inclusion criteria^1,2

Confirmed α-mannosidase activity (<10% of normal activity in blood leukocytes)
Ability to cooperate physically and mentally in trial assessments

Exclusion criteria²

Presence of known chromosomal abnormality and syndromes, other than alpha-mannosidosis
Inability to walk without support (the use of walking aids/wheelchair for partial support and longer distances was permitted)
History of bone marrow transplantation
Any psychotic disease, active or in remission
Total immunoglobulin E (lgE) >800 IU/mL

Eligibility was not limited by motor performance at baseline.

Demonstrated favorable response vs placebo in both co-primary endpoints.¹

Co-primary endpoints²

Serum oligosaccharides change from baseline to week 52
3-minute stair-climbing test (3MSCT)

Reduction in a key marker of impaired cellular function¹

Improvements at 6 months that continued at 1 year

	Lamzede	Placebo
Baseline (SD)	6.8 (1.2)	6.6 (1.9)
Mean relative change % (SD)	-75.8% (11.2)	-20.3% (24.0)

Lamzede reduced oligosaccharides by 75.8%.¹

Maintained endurance climbing stairs, as measured by the 3MSCT¹

Patients who received placebo declined over time

	Lamzede	Placebo
Baseline (SD)	52.9 (11.2)	55.5 (16.0)
Mean relative change % (SD)	+0.5% (16.1)	-3.6% (13.1)

Lamzede patients showed a slight increase in steps per minute after 1 year.^1,*

*Differences in 3MSCT were not statistically significant.

See 6MWT
and FVC% data

	Lamzede	Placebo
Baseline (SD)	459.6 (72.3)	465.7 (140.5)
Mean relative change % (SD)	+1.2% (9.8)	-0.8% (10.8)

^†Differences in 6MWT were not statistically significant.

	Lamzede	Placebo
Baseline (SD)	81.7 (20.7)	90.4 (10.4)
Mean relative change % (SD)	+11.4% (13.1)	+1.9% (15.4)

^‡Differences in FVC test were not statistically significant.

^†Differences in 6MWT were not statistically significant.

^‡Differences in FVC test were not statistically significant.

1.	Lamzede. Prescribing Information. Chiesi Farmaceutici S.p.A; 2023.
2.	Borgwardt L, Guffon N, Amraoui Y, et al. Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial. J Inherit Metab Dis. 2018;41(6):1215-1223. doi:10.1007/s10545-018-0185-0.
3.	Lund AM, Borgwardt L, Cattaneo F, et al. Comprehensive long-term efficacy and safety of recombinant human alpha-mannosidase (velmanase alfa) treatment in patients with alpha-mannosidosis. J Inherit Metab Dis. 2018;41(6):1225-1233. doi:10.1007/s10545-018-0175-2.
4.	Guffon N, Tylki-Szymanska A, Borgwardt L, et al. Recognition of alpha-mannosidosis in paediatric and adult patients: presentation of a diagnostic algorithm from an international working group. Mol Gen Metab. 2019;126(4):470-474. doi:10.1016/j.ymgme.2019.01.024.
5.	Borgwardt L, Stensland HMFR, Olsen KJ, et al. Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Orphanet J Rare Dis. 2015;10:70. doi:10.1186/s13023-015-0286-x.
6.	Beck M, Olsen KJ, Wraith JE, et al. Natural history of alpha mannosidosis a longitudinal study. Orphanet J Rare Dis. 2013;8:88. doi:10.1186/1750-1172-8-88.
7.	Malm D, Nilssen Ø. Alpha-mannosidosis. Orphanet J Rare Dis. 2008;3:21. doi:10.1186/1750-1172-3-21.

1.	Lamzede. Prescribing Information. Chiesi Farmaceutici S.p.A; 2023.
2.	Borgwardt L, Lund AM, Dali CI. Alpha-mannosidosis—a review of genetic, clinical findings and options for treatment. Pediatr Endocrinol Rev. 2014;12(suppl1):185-191.
3.	Borgwardt L, Stensland HMFR, Olsen KJ, et al. Alpha-mannosidosis: correlation between phenotype, genotype and mutant MAN2B1 subcellular localisation. Orphanet J Rare Dis. 2015;10:70. doi:10.1186/s13023-015-0286-x.
4.	Beck M, Olsen KJ, Wraith JE, et al. Natural history of alpha mannosidosis a longitudinal study. Orphanet J Rare Dis. 2013;8:88. doi:10.1186/1750-1172-8-88.
5.	Wiesinger T, Schwarz M, Mechtler TP, et al. α-Mannosidosis—An underdiagnosed lysosomal storage disease in individuals with an ‘MPS-like’ phenotype. Mol Genet Metab. 2020;130(2):149-152. doi:10.1016/j.ymgme.2020.04.001
6.	Malm D, Nilssen Ø. Alpha-mannosidosis. Orphanet J Rare Dis. 2008;3:21. doi:10.1186/1750-1172-3-21.
7.	Guffon N, Tylki-Szymanska A, Borgwardt L, et al. Recognition of alpha-mannosidosis in paediatric and adult patients: presentation of a diagnostic algorithm from an international working group. Mol Gen Metab. 2019;126(4):470-474. doi:10.1016/j.ymgme.2019.01.024.

1.	Lamzede. Prescribing Information. Chiesi Farmaceutici S.p.A; 2023.
2.	Guffon N, Tylki-Szymanska A, Borgwardt L, et al. Recognition of alpha-mannosidosis in paediatric and adult patients: presentation of a diagnostic algorithm from an international working group. Mol Gen Metab. 2019;126(4):470-474. doi:10.1016/j.ymgme.2019.01.024.
3.	Wiesinger T, Schwarz M, Mechtler TP, et al. α-Mannosidosis—An underdiagnosed lysosomal storage disease in individuals with an ‘MPS-like’ phenotype. Mol Genet Metab. 2020;130(2):149-152. doi:10.1016/j.ymgme.2020.04.001
4.	Malm D, Nilssen Ø. Alpha-mannosidosis. Orphanet J Rare Dis. 2008;3:21. doi:10.1186/1750-1172-3-21.

1.	Lamzede. Prescribing Information. Chiesi Farmaceutici S.p.A; 2023.
2.	Borgwardt L, Lund AM, Dali CI. Alpha-mannosidosis – a review of genetic, clinical findings and options for treatment. Pediatr Endocrinol Rev. 2014;12(suppl1):185-191.
3.	The natural history of alpha-mannosidosis (HUE-MAN). ClinicalTrials.gov identifier: NCT00498420. Updated August 3, 2020. Accessed December 23, 2022. https://clinicaltrials.gov/ct2/show/NCT00498420.
4.	Safety study of recombinant human alpha-mannosidase for the treatment of patients with alpha-mannosidosis. ClinicalTrials.gov identifier: NCT01268358. Updated August 3, 2020. Accessed December 23, 2022. https://clinicaltrials.gov/ct2/show/NCT01268358.
5.	Dose finding study of recombinant human alpha-mannosidase for the treatment of patients with alpha-mannosidosis. ClinicalTrials.gov identifier: NCT01285700. Updated September 26, 2012. Accessed December 23, 2022. https://clinicaltrials.gov/ct2/show/NCT01285700.
6.	Long-term efficacy and safety of lamazym for the treatment of patients with alpha-mannosidosis. ClinicalTrials.gov identifier: NCT01681940. Updated March 29, 2017. Accessed December 23, 2022. https://clinicaltrials.gov/ct2/show/NCT01681940.
7.	Trial on safety and efficacy of velmanase alfa treatment in pediatric patients with alpha-mannosidosis (rhLaman-08). ClinicalTrials.gov identifier: NCT02998879. Updated October 26, 2021. Accessed December 23, 2022. https://clinicaltrials.gov/ct2/show/NCT02998879.
8.	A placebo-controlled phase 3 trial of repeated lamazym treatment of subjects with alpha-mannosidosis. ClinicalTrials.gov identifier: NCT01681953. Updated August 3, 2020. Accessed December 23, 2022. https://clinicaltrials.gov/ct2/show/NCT01681953.
9.	Borgwardt L, Guffon N, Amraoui Y, et al. Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial. J Inherit Metab Dis. 2018;41(6):1215-1223. doi: 10.1007/s10545-018-0185-0.
10.	Lund AM, Borgwardt L, Cattaneo F, et al. Comprehensive long-term efficacy and safety of recombinant human alpha-mannosidase (velmanase alfa) treatment in patients with alpha-mannosidosis. J Inherit Metab Dis. 2018;41(6):1225-1233. doi:10.1007/s10545-018-0175-2.
11.	Evaluation of long-term efficacy of treatment with lamazym (rhLAMAN-10). ClinicalTrials.gov identifier: NCT02478840. Updated November 20, 2020. Accessed December 23, 2022. https://clinicaltrials.gov/ct2/show/NCT02478840.

Proven to deliver results for both adults and children in a 1-year trial2

Demonstrated favorable results in both pharmacodynamic and functional measures1

Study design

Efficacy and safety assessed in 25 patients with this ultra-rare disease.2

Inclusion criteria1,2

Exclusion criteria2

Co-primary endpoints2

Reduction in a key marker of impaired cellular function1

Maintained endurance climbing stairs, as measured by the 3MSCT1

Proven to deliver results
for both adults and
children in a 1-year trial²

Demonstrated favorable results in both pharmacodynamic and functional measures¹

Efficacy and safety assessed in 25 patients with this ultra-rare disease.²

Inclusion criteria^1,2

Exclusion criteria²

Co-primary endpoints²

Reduction in a key marker of impaired cellular function¹

Maintained endurance climbing stairs, as measured by the 3MSCT¹