SHORT SUMMARY

CIPAGLUCOSIDE alfa alfa-(Aug 2023)

Indn-  To  treat major depressive disorder      

Comp-   For injection: 105 mg of cipaglucosidase alfa-atga as a lyophilized powder in a single-dose vial for reconstitution.                                                                           Recommended POMBILITI dosage is 20 mg/kg (of actual body weight) administered every other week as an intravenous infusion over approximately 4 hours. Start POMBILITI in combination with Opfolda 2 weeks after the last ERT dose

ADR-  Most common adverse reactions = 5% are headache, diarrhea, fatigue, nausea, abdominal pain, and pyrexia. 

CI- Pregnancy 

WARNINGS-

 Embryo-Fetal Toxicity: May cause embryo-fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for at least 60 days after the last dose.

Pat Inform-

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 POMBILITI in combination with Opfolda treatment, including anaphylactic reactions, other serious or severe hypersensitivity reactions, and IARs.

Risk of Acute Cardiorespiratory Failure-                                                                 Advise the patient and caregiver that a patient with underlying respiratory illness or compromised cardiac or respiratory function may be at risk of acute cardiorespiratory failure from volume overload during POMBILITI infusion

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U.S.  APPROVED DRUGS DURING 2023                                        

Serial No 39

Name-                      POMMBILITI

Acive  Ingredient -  Cipaglucoside alfa alfa

Pharmacological clssificiation-        To  treat major depressive disorder                                                                                                                   

Date  of approval                   9/8/2023 

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all the information needed to use                                         POMBILITI™ safely and effectively.

See full prescribing information for POMBILITI. POMBILITI (cipaglucosidase alfa-atga) for injection, for intravenous use

Initial U.S. Approval: 2023

WARNING:                                                                                                                    SEVERE HYPERSENSITIVITY REACTIONS, INFUSION-ASSOCIATED REACTIONS, and RISK OF ACUTE CARDIORESPIRATORY FAILURE IN SUSCEPTIBLE PATIENTS

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, POMBILITI should be discontinued immediately and appropriate medical treatment should be initiated.

 Infusion-Associated Reactions (IARs) -                                                                         If severe IARs occur, immediately discontinue POMBILITI and initiate appropriate medical treatment.

 Risk of Acute Cardiorespiratory Failure in Susceptible Patients -                             Patients susceptible to fluid volume overload, or those with acute underlying respiratory illness or compromised cardiac or respiratory function, may be at risk of serious exacerbation of their cardiac or respiratory status during POMBILITI infusio

INDICATIONS AND USAGE-

 POMBILITI is a hydrolytic lysosomal glycogen-specific enzyme indicated, in combination with Opfolda, an enzyme stabilizer, for the treatment of adult patients with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency) weighing =40 kg and who are not improving on their current enzyme replacement therapy (ERT

ADVERSE REACTIONS-

 Most common adverse reactions = 5% are headache, diarrhea, fatigue, nausea, abdominal pain, and pyrexia. 

CONTRAINDICATIONS-

 Pregnancy 

WARNINGS AND PRECAUTIONS-

See boxed warning.

 Embryo-Fetal Toxicity: May cause embryo-fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for at least 60 days after the last dose.

 Risks Associated with Opfolda: Refer to the Opfolda Prescribing Information for a description of additional risks for Opfolda

DOSAGE AND ADMINISTRATION-

 Verify pregnancy status in females of reproductive potential prior to initiating treatment.  Administer POMBILITI in combination with Opfolda.

  Recommended POMBILITI dosage is 20 mg/kg (of actual body weight) administered every other week as an intravenous infusion over approximately 4 hours. Start POMBILITI in combination with Opfolda 2 weeks after the last ERT dose

 Initiate the POMBILITI infusion approximately 1 hour after oral administration of Opfolda.

If the POMBILITI infusion cannot be started within 3 hours of oral administration of Opfolda, reschedule POMBILITI in combination with Opfolda at least 24 hours after Opfolda was last taken.

If POMBILITI in combination with Opfolda are both missed, re-start treatment as soon as possible.

 See the full prescribing information for dosage modifications due to hypersensitivity reactions or IAR

 Must be reconstituted and diluted prior to use.  See the full prescribing information for administration instructions. 

DOSAGE FORMS AND STRENGTHS-

 For injection: 105 mg of cipaglucosidase alfa-atga as a lyophilized powder in a single-dose vial for reconstitution.

PATIENT COUNSELING INFORMATION-

POMBILITI must be administered in combination with Opfolda. Refer to the Opfolda Prescribing Information for Opfolda patient counseling information.

Administration-                                                                                                         Advise the patient and caregiver to follow the timeline recommendations for taking Opfolda prior to the intravenous infusion with POMBILITI 

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 POMBILITI in combination with Opfolda 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

Risk of Acute Cardiorespiratory Failure-                                                                 Advise the patient and caregiver that a patient with underlying respiratory illness or compromised cardiac or respiratory function may be at risk of acute cardiorespiratory failure from volume overload during POMBILITI infusion

Embryo-Fetal Toxicity-                                                                                                  POMBILITI in combination with Opfolda may cause embryo-fetal harm. Advise a female patient and caregiver to inform their healthcare provider of a known or suspected pregnanc

Advise a female of reproductive potential to use effective contraception during treatment with POMBILITI in combination with Opfolda and for at least 60 days after the last dose

Lactation-                                                                                                                      Advise a lactating female not to breastfeed during treatment with POMBILITI in combination with Opfolda

 Infertility-                                                                                                                            Advise the male or female of reproductive potential that POMBILITI in combination with Opfolda may impair fertility

Manufactured by: Amicus Therapeutics US, LLC 3675 Market Street Philadelphia, PA 19104 U.S. License No. xxxx POMBILITI and Opfolda are trademarks of Amicus Therapeutics, Inc.

CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                             Pompe disease (also known as glycogen storage disease type II, acid maltase deficiency, and glycogenosis type II) is an inherited disorder of glycogen metabolism caused by a deficiency of lysosomal acid alpha-glucosidase (GAA) that degrades glycogen to glucose in the lysosome.

2. Pharmacokinetics-                                                                                                       The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of cipaglucosidase alfa-atga following administration with 20 mg/kg of cipaglucosidase alfa-atga in combination with a single oral dose of 260 mg of Opfolda in adult patients 

Elimination-                                                                                                                        When cipaglucosidase alfa-atga was administered with Opfolda, the mean total body clearance (CL) of cipaglucosidase alfa-atga was 0.8 L/hour and the mean half-life of cipaglucosidase alfa-atga was 2.1 hours in ERT-experienced patients.

Metabolism-                                                                                                                   The metabolic pathway of cipaglucosidase alfa-atga has not been characterized. Cipaglucosidase alfa-atga is expected to be metabolized into small peptides and amino acid via catabolic pathways.

4.Specific Populations-                                                                                                        Age (18 to 74 years) and sex did not have clinically meaningful effects on the pharmacokinetics of cipaglucosidase alfa-atga.

5. Immunogenicity-                                                                                                          The observed incidence of antidrug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of antidrug antibodies (ADA) in the trials described below with the incidence of antidrug antibodies in other trials, including those of cipaglucosidase alfa-atg

USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-                                                                                    Based on findings from animal reproduction studies, POMBILITI in combination with Opfolda may cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy.

2. Lactation Risk Summary -                                                                                     There are no data on the presence of cipaglucosidase alfa-atga, alone or in combination with miglustat, in human milk, the effects on the breastfed infant, or the effects on milk production. Cipaglucosidase alfa-atga is present in animal milk 

3. Females and Males of Reproductive Potential-                                                         POMBILITI in combination with Opfolda may cause embryo-fetal harm when administered to a pregnant female [see Use in Specific Populations (8.1)].

Pregnancy Testing-                                                                                                       Verify the pregnancy status in females of reproductive potential prior to initiating treatment with POMBILITI in combination with Opfolda.

Contraception Females-                                                                                                 Advise females of reproductive potential to use effective contraception during treatment with POMBILITI in combination with Opfolda and for at least 60 days after the last dose. 13 Reference ID: 5252147

Infertility Females -                                                                                                      Based on preimplantation loss observed in female rats treated with intravenous cipaglucosidase alfa-atga (400 mg/kg) in combination with oral miglustat (60 mg/kg) every other day for 14 days prior to mating, and continuing through GD 7, POMBILITI in combination with Opfolda may impair human female fertility. A NOAEL for the combination was not identified.

5.Safety and effectiveness of POMBILITI in combination with Opfolda have not been established in pediatric patients with late-onset Pompe disease.

6. Geriatric Use -                                                                                                               Of the total number of patients treated with POMBILITI in combination with Opfolda in clinical trials for LOPD, 17 (11%) were 65 to 74 years of age, and none were 75 years of age and older [see Clinical Studies (14)].

Clinical trials of POMBILITI in combination with Opfolda did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.