BRIEF SUMMARY-

VELMANASE-alfa- (FEB 2030)

Indn- To  treat non-central nervous system manifestations of alpha- mannosidosis  

Dosage- For injection: 10 mg of velmanase alfa-tycv as a lyophilized powder in a single-dose vial for reconstitution. Recommended dosage is 1 mg/kg (actual body weight) administered once every week as an intravenous infusion.

ADR- Most common adverse reactions (incidence > 20%) are hypersensitivity reactions including anaphylaxis, nasopharyngitis, pyrexia, headache, and arthralgia.

CI- None.

WARNINGS- Infusion-Associated Reactions (IARs): If severe IARs occur, discontinue drug  and initiate appropriate medical treatment.                                                     

 Embryo-Fetal 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 discontinued.

Pat Inform-  

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U.S.  APPROVED DRUGS DURING 2023                                        

Serial No 6

Name-        LAMZEDE

Acive  Ingredient -  Velmanase alfa-tycv

 Pharmacological clssificiation-        To  treat non-central nervous system                                                                              manifestations of alpha- mannosidosis                                                                                                                                                                   

Date of Approval-         2/16/2023 

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use                               LAMZEDE® safely and effectively.                                                                               See full prescribing information for LAMZEDE. LAMZEDE (velmanase alfa-tycv) for injection, for intravenous use.

Initial U.S. Approval: 2023

WARNING:                                                                                                             SEVERE HYPERSENSITIVITY REACTIONS See full prescribing information for complete boxed warning.

Hypersensitivity Reactions- Including Anaphylaxis                                                          • Appropriate medical support measures, including cardiopulmonary resuscitation equipment, should be readily available.                                                                             If a severe hypersensitivity reaction occurs, discontinue LAMZEDE immediately and initiate appropriate medical treatment. 

INDICATIONS AND USAGE-

 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.

ADVERSE REACTIONS-

 Most common adverse reactions (incidence > 20%) are hypersensitivity reactions including anaphylaxis, nasopharyngitis, pyrexia, headache, and arthralgia.

CONTRAINDICATIONS-

 None.

WARNINGS AND PRECAUTIONS-

 • Infusion-Associated Reactions (IARs): If severe IARs occur, discontinue LAMZEDE and initiate appropriate medical treatment.

 • Embryo-Fetal 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.

DOSAGE AND ADMINISTRATION-

 • For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment.

 • Consider pretreating with antihistamines, antipyretics, and/or corticosteroids prior to LAMZEDE administration.

 • Recommended LAMZEDE dosage is 1 mg/kg (actual body weight) administered once every week as an intravenous infusion.

 • See the full prescribing information for dosage modifications due to hypersensitivity reactions or IARs. 

See the full prescribing information for reconstitution and administration instructions.

DOSAGE FORMS AND STRENGTHS-

 For injection: 10 mg of velmanase alfa-tycv as a lyophilized powder in a single-dose vial for reconstitution.

PATIENT COUNSELING INFORMATION-

 Hypersensitivity Reactions-

Including Anaphylaxis and Infusion-Associated Reactions (IARs)

Advise the patient and caregiver that reactions related to the infusion may occur during and after LAMZEDE treatment, including anaphylactic reactions, other serious or severe hypersensitivity reactions, and IARs.

Inform the patient and caregiver of the signs and symptoms of hypersensitivity reactions and IARs and to seek medical care should signs and symptoms occur.

Embryo-Fetal Toxicity- LAMZEDE may cause embryo-fetal harm. Advise the pregnant female of the potential risk to the fetus.

Advise a female patient and caregiver to inform their healthcare provider of a known or suspected pregnancy.

Advise a female of reproductive potential to use effective contraception during treatment and for 14 days after the last dose if LAMZEDE is discontinued.

Manufactured by: Chiesi Farmaceutici S.p.A. Via Palermo 26/A, 43122 Parma, Italy U.S. License No. 2245 Manufactured at: Patheon Italia S.p.A., Ferentino FR, Italy, 03013 Manufactured for: Chiesi USA, Inc., Cary NC, 27518, USA. Product of Germany. LAMZEDE is a registered trademark of Chiesi Farmaceutici S.p.A. CTVA-001-0222-00-

CLINICAL PHARMACOLOGY

1. Mechanism of Action -                                                                                         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. Alphamannosidase catalyzes the degradation of accumulated mannose-containing oligosaccharides.

2. Pharmacodynamics- Serum oligosaccharide concentrations are elevated in patients with alpha-mannosidosis. In clinical studies, serum oligosaccharide concentrations were quantified by assessment of 2-mannose oligosaccharides.

3. Pharmacokinetics- The pharmacokinetics of velmanase alfa-tycv were evaluated in adult patients with alphamannosidosis and are presented as mean (standard deviation, SD) unless otherwise specified.

Distribution- The volume of distribution of velmanase alfa-tycv was 276 (43) mL/kg in patients with alphamannosidosis.

Elimination- The total body clearance of velmanase alfa-tycv was 5.7 (0.9) mL/h/kg and the mean terminal half-life (t1/2) was 33.6 hours in patients with alpha-mannosidosis.

Metabolism- Velmanase alfa-tycv is expected to be metabolized into small peptides by catabolic pathways.

Specific Population-                                                                                               Pediatric Patients In pediatric patients (6 to 17 years of age) with alpha-mannosidosis, the Cmax and AUC0-t at steady state were 6.6 (1.0) µg/mL and 109.8 (17.8) µg·h/mL, respectively, at the recommended dose of 1 mg/kg velmanase alfa-tycv administered once a week.

Immunogenicity- The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay.

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary

Based on findings from animal reproduction studies, LAMZEDE may cause embryo-fetal harm when administered to a pregnant female.

. 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. general population, the estimated background risk of major birth defects and 0miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

2 Lactation Risk Summary-                                                                                              There are no data on the presence of velmanase alfa-tycv or its metabolite in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LAMZEDE and any potential adverse effects on the breastfed infant from velmanase alfa-tycv or from the underlying maternal condition.

3. Females and Males of Reproductive Potential-                                           LAMZEDE may cause embryo-fetalharm when administered to a pregnant female [see

Pregnancy Testing For females of reproductive potential, verify that the patient is not pregnant prior to initiating treatment with LAMZEDE

 Contraception Females- Advise females of reproductive potential to use effective contraception during treatment and for 14 days after the last dose if LAMZEDE is discontinued.

4. Pediatric Use-                                                                                                                The safety and effectiveness of LAMZEDE for the treatment of alpha-mannosidosis have been established in pediatric patients.

5. Geriatric Use-                                                                                                       Alpha-mannosidosis is largely a disease of pediatric and young adult patients. Clinical trials of LAMZEDE did not include patients 65 years of age and older.