Long-Term Outcomes in Alpha-Mannosidosis

In the Trial 3 integrated analysis (N=33), investigators pooled the cumulative databases from Lamzede Phase I, II, and III trials in patients with alpha-mannosidosis^2,*

20 male and 13 female patients aged 6 to 35 years old (14 adults, 19 pediatric) received Lamzede weekly for a mean exposure of 89 weeks in adult patients and 155 weeks in pediatric patients
Overall mean exposure was 29.3 (15.2 SD) months

Phase I and II
(follow-up to 48 months)

Phase III
(active for 12-36 months)^†

Phase III (placebo for 12 months and then active to month 36)^‡

Phase I, II and III^§
(only 12 months data)

Lamzede delivers sustained results over time.²

Co-primary endpoints²

Serum oligosaccharides change from baseline to last observation
3-minute stair-climbing test (3MSCT) from baseline to last observation

Serum oligosaccharides²

Similar results were seen across age groups

3MSCT²

A greater difference was seen in pediatric patients

*	The integrated study design was necessary to assess long-term efficacy and safety in a progressively worsening disease despite the rarity of patient population. Although the placebo-control period was limited to 12 months, duration of follow-up and repeated assessments were designed to mitigate that limitation. Additionally, while the mean and median durations of exposure exceed 2 years, only a small proportion of patients in the developmental program have non-missing efficacy measurements after 18 months. Therefore, the ability of the integrated analysis to provide interpretable evidence of long-term efficacy is unclear.
^†	One patient was originally in Phase I/II trials, but is only counted as part of Phase III.
^‡	One patient was in the placebo group of Phase III pivotal trial, and continued in both the compassionate use program and an extension trial. Patient data is only counted once.
^§	One patient was in the active Phase III pivotal trial, and continued in the compassionate use program, but did not participate in the long-term extension. Therefore, data represents 12 months.

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.

Lamzede showed pharmacodynamic and functional improvement over the long term—up to 4 years2

Co-primary endpoints2

Lamzede showed pharmacodynamic
and functional improvement over
the long term—up to 4 years²

Co-primary endpoints²