Velmanase Alfa

Alpha-mannosidosis is a lysosomal storage disease that results from reduced activity of the enzyme alpha-mannosidase, caused by gene variants in Mannosidase Alpha Class 2B Member 1. Alpha-mannosidase catalyzes the degradation of accumulated mannose-containing oligosaccharides.

• INDICA TIONS AND USAGE LAMZEDE is indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients. LAMZEDE is recombinant human lysosomal alpha-mannosidase indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients.

• None. None.contraindicated

For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment. ( 2.1 ) Consider pretreating with antihistamines, antipyretics, and/or corticosteroids prior to LAMZEDE administration. ( 2.2 ) Recommended LAMZEDE dosage is 1 mg/kg (actual body weight) administered once every week as an intravenous infusion. ( 2.2 ) See the full prescribing information for dosage modifications due to hypersensitivity reactions or IARs. ( 2.3 ) See the full prescribing information for reconstitution and administration instructions. ( 2.4 , 2.5 ) 2.1 Important Recommendations Prior to LAMZEDE Treatment Initiation For females of reproductive potential, verify that the patient is not pregnant [see Use in Specific Populations ( 8.1 , 8.3 )] . 2.2 Recommended Dosage and Administration Prior to LAMZEDE administration, consider pre-treating with antihistamines, antipyretics, and/or corticosteroids [see Warnings and Precautions ( 5.1 , 5.2 )] . The recommended dosage of LAMZEDE is 1 mg/kg (actual body weight) administered once every week as an intravenous infusion. The total volume of infusion is determined by the patient’s actual body weight and should be administered over a minimum of 60 minutes for patients weighing up to 49 kg. Patients weighing 50 kg and greater should be infused at a maximum infusion rate of 25 mL/hour to control the protein load [ s ee Dosage and Administration ( 2.4 )] . If one or more doses are missed, restart the treatment as soon as possible, as long as it is at least 3 days from the next scheduled dose.

Infusion -Associ ated Reactions (IARs) : If severe IARs occur, discontinue LAMZEDE and initiate appropriate medical treatment. ( 5.2 ) Embryo - F etal Toxicity : May cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for 14 days after the last dose if LAMZEDE is discontinued. ( 5.3 , 8.1 , 8.3 ) 5.1 Hypersensitivity Reactions Including Anaphylaxis Hypersensitivity reactions including anaphylaxis have been reported in LAMZEDE-treated patients. In clinical trials, 19 (50%) LAMZEDE-treated patients (5 adult patients and 14 pediatric patients) experienced hypersensitivity reactions, including 2 (5%) patients (1 adult patient and 1 pediatric patient) who experienced anaphylaxis and an additional 3 (8%) pediatric patients who experienced severe hypersensitivity reactions that required medical treatment [see Clinical Studies ( 14 )] . In the 5 patients who experienced anaphylaxis or severe hypersensitivity requiring medical treatment, 4 (80%) were anti-drug antibody (ADA) positive [see Clinical Pharmacology ( 12.6 ) ] . Anaphylaxis and severe hypersensitivity signs and symptoms included cyanosis, hypotension, emesis, urticaria, erythema, facial swelling, pyrexia, and tremor. Prior to LAMZEDE administration, consider pretreating with antihistamines, antipyretics, and/or corticosteroids. Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available during LAMZEDE administration.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions Including Anaphylaxis [see Warnings and Precautions ( 5.1 )] Infusion-Associated Reactions (IARs) [see Warnings and Precautions ( 5.2 ) ] Most common adverse reactions (incidence > 20%) are hypersensitivity reactions including anaphylaxis ( 5.1 ), nasopharyngitis, pyrexia, headache, and arthralgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chiesi USA, Inc. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions F rom Trial 1 The safety of LAMZEDE was evaluated in Trial 1, which included a total of 15 LAMZEDE-treated patients (8 adult patients aged 18-35 years old and 7 pediatric patients aged 6-17 years old; 9 male, 6 female) with alpha-mannosidosis [see Clinical Studies ( 14 )]. All patients received LAMZEDE 1 mg/kg weekly via intravenous infusion for 52 weeks. A serious adverse reaction of acute renal failure was reported in 1 (7%) LAMZEDE-treated patient (see Description of Selected Adverse Reactions) . Table 1 lists adverse reactions that occurred in at least 2 LAMZEDE-treated patients in Trial 1.

8.1 Pregnancy Risk Summary Based on findings from animal reproduction studies, LAMZEDE may cause embryo-fetal harm when administered to a pregnant female. In animal reproduction studies, major visceral malformations were observed in rats and rabbits when velmanase alfa-tycv was administered in pregnant rats and rabbits during the period of organogenesis. These malformations were observed in rats at the highest dose level, at exposures that were approximately 7-fold the recommended dose in patients of 1 mg/kg. Malformations occurred at all dose levels in rabbits with the highest dose exposures approximately 2.5-fold the recommended patient dose of 1 mg/kg ( see Data ) . There are no available data on LAMZEDE use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Advise the pregnant female of the potential risk to the fetus. The decision to continue or discontinue LAMZEDE treatment during pregnancy should consider the female’s need for LAMZEDE, the potential drug-related risks to the fetus, and the potential adverse outcomes from untreated maternal disease. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S.

Metabolism

The pharmacokinetics of velmanase alfa-tycv were evaluated in adult patients with alpha-mannosidosis and are presented as mean (standard deviation, SD) unless otherwise specified. The steady state maximum plasma velmanase alfa-tycv concentration (C max ) was 7.9 (0.9) μg/mL and area under the concentration-time curve (AUC 0-t ) was 159.8 (24.4) μg∙h/mL at the approved recommended dosage of 1 mg/kg.

• Feb 16, 2023BLABLA761278Chiesi Farmaceutici Spa

1. 1Product Dose Omission Issue611%
2. 2Product Complaint59.3%
3. 3Pyrexia59.3%
4. 4Off Label Use47.4%
5. 5Product Administration Interrupted47.4%
6. 6Vomiting47.4%
7. 7Abdominal Pain35.6%
8. 8Arthropathy35.6%
9. 9Infusion Related Reaction35.6%
10. 10Urticaria35.6%
11. 11Blood Creatinine Increased23.7%
12. 12C-reactive Protein Increased23.7%
13. 13Contusion23.7%
14. 14Diarrhoea23.7%
15. 15Dyspnoea23.7%

The 10 most recently updated of 11 ClinicalTrials.gov registrations naming Velmanase Alfa as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Analysis of Velmanase Alfa (Lamzede®)'s Effects in the Body of Children With Alpha-Mannosidosis Under the Age 3
  Recruiting · Observational · 5 enrolled · Chiesi Farmaceutici S.p.A.
  NCT06184503updated 2025-05-16
• Expanded Access to Velmanase Alfa
  Available · Expanded access · Chiesi Farmaceutici S.p.A.
  NCT04959240updated 2023-09-25
• Lamazym Aftercare Study FR Designed to Provide Treatment for French Patients
  Completed · Phase 3 · Interventional · 13 enrolled · Chiesi Farmaceutici S.p.A.
  NCT01908712updated 2023-07-28
• Lamazym Aftercare Study
  Completed · Phase 3 · Interventional · 8 enrolled · Chiesi Farmaceutici S.p.A.
  NCT01908725updated 2023-07-28
• Trial on Safety and Efficacy of Velmanase Alfa Treatment in Pediatric Patients With Alpha-Mannosidosis
  Completed · Phase 2 · Interventional · 5 enrolled · Chiesi Farmaceutici S.p.A.
  NCT02998879updated 2021-10-26
• Interventional Study to Assess Efficacy and Safety of Velmanase Alfa in Patients With Alpha Mannosidosis
  Withdrawn · Phase 3 · Interventional · 0 enrolled · Chiesi Farmaceutici S.p.A.
  NCT04031066updated 2020-12-08
• Evaluation of Long-term Efficacy of Treatment With Lamazym
  Completed · Phase 3 · Interventional · 18 enrolled · Zymenex A/S
  NCT02478840updated 2020-11-20
• Safety Study of Recombinant Human Alpha-mannosidase for the Treatment of Patients With Alpha-mannosidosis
  Completed · Phase 1 · Interventional · 10 enrolled · Zymenex A/S
  NCT01268358updated 2020-08-03
• A Placebo-Controlled Phase 3 Trial of Repeated Lamazym Treatment of Subjects With Alpha-Mannosidosis
  Completed · Phase 3 · Interventional · 25 enrolled · Zymenex A/S
  NCT01681953updated 2020-08-03
• Long-term Efficacy and Safety of Lamazym for the Treatment of Patients With Alpha-Mannosidosis
  Completed · Phase 2 · Interventional · 10 enrolled · Zymenex A/S
  NCT01681940updated 2017-03-29

Frequently asked questions

How does Velmanase Alfa work?

Alpha-mannosidosis is a lysosomal storage disease that results from reduced activity of the enzyme alpha-mannosidase, caused by gene variants in Mannosidase Alpha Class 2B Member 1. Alpha-mannosidase catalyzes the degradation of accumulated mannose-containing oligosaccharides.

What is Velmanase Alfa used for?

According to FDA labeling, Velmanase Alfa carries indications including: INDICA TIONS AND USAGE LAMZEDE is indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients. LAMZEDE is recombinant human lysosomal alpha-mannosidase indicated for the treatment of non-central nervous system manifestations of alpha-mannosidosis in adult and pediatric patients.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Velmanase Alfa?

Velmanase Alfa is classified as Enzymes.

What are the brand names for Velmanase Alfa?

Velmanase Alfa is marketed under brand names including Lamzede.

What are the contraindications for Velmanase Alfa?

Velmanase Alfa labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.