HomeNDC LookupIngredientsMetreleptin › 10122-0210-02
Myalept metreleptin 11.3 mg/2.2mL Injection, Powder, Lyophilized, For Solution, 1 vial — NDC 10122-0210-02 package photo

Myalept metreleptin 11.3 mg/2.2mL Injection, Powder, Lyophilized, For Solution, 1 vial

by Chiesi USA, Inc. · 1 VIAL, GLASS in 1 CARTON (10122-210-02) / 2.2 mL in 1 VIAL, GLASS
NDC 10122-0210-02
🏷️ FDA NDC (as labeled) 10122-210-02 billing pads the product segment with a zero
Rx only Brand On market Non-controlled 🛡 REMS
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

🆔 Identity & classification

FDA NDC (as labeled) 10122-210-02
Product NDC 10122-210
11-digit billing NDC 10122021002
NCPDP billing unit EA — each (per item)
RxCUI 1491629, 1491634
UNII TL60C27RLH
UPC 0310122210028
Application # BLA125390
SPL Set ID d3b50bbd-140b-425c-b5ec-d4682aad62bc
Established class (EPC) Leptin Analog
Chemical class Analogs/Derivatives; Leptin
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2015-03-05
Route SUBCUTANEOUS
Dosage form INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Substance METRELEPTIN
GPI-14 30906050002120
GCN Seq No 072265
GCN 36398
HICL code 041078
Ingredient (HICL) Metreleptin
HIC1 code P
Therapeutic class — broad (HIC1) Endocrine System
HIC2 code P8
Therapeutic class — intermediate (HIC2) Adipose Tissue Hormones
HIC3 code P8A
Therapeutic class — specific (HIC3) Leptin Hormone Analogs
AHFS code 68:40.00.00
AHFS class Leptins
FDB label name MYALEPT 11.3 MG (5 MG/ML) VIAL
FDB brand name Myalept
Legend status F — Federal legend — prescription drug or device
Biologic (Purple Book) 351(a)
Why two NDCs? The FDA registers this code as 10122-210-02 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 10122-0210-02. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Leptin Analog class.

Pharmacologic class Leptin Analog
Drug family (ATC) Amino acids and derivatives
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerChiesi USA, Inc.
FDA applicationBLA125390 (BLA)
Labeler code10122
First marketedMar 2015
Product typeHuman Prescription Drug
Portfolio25 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name MYALEPT 11.3 MG (5 MG/ML) VIAL Ingredient Metreleptin
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII 3KX376GY7L
    Glutamic acid is an amino acid used in pharmaceuticals as a buffer and pH regulator. It helps maintain the medicine's chemical stability and proper acidity level.
  • UNII TE7660XO1C
    Glycine is an amino acid used in medicines as a buffer to help stabilize pH and improve taste. It may also serve as a filler or binder to give the product proper form and consistency.
  • UNII 7T1F30V5YH
    A synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together and keeps them from separating in liquid formulations.
  • UNII C151H8M554
    A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.

4 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMedingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $6,455.65 $14,202.42 / 2.2 ml
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Myalept 11.3 mg/2.2mLthis 10122-0210-02 Chiesi 1 vial FDA listed
About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & biosimilar status

🏛️
2014
First FDA approval
Feb 2014
📍
2026
Currently FDA-listed
12 years listed
🔓
·
Biosimilar pathway open
listed protections lapsed 2026
🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

🛡️ Latest patent/protection date listed: The latest listed FDA patent/protection lapsed Feb 2026 — those protections no longer apply, though a biosimilar still needs FDA licensure and a manufacturer to market it.
📅 FDA approved Feb 24, 2014

Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.

FDA Purple Book — biosimilars & interchangeables
Reference product
🔒 No FDA-licensed biosimilars or interchangeable biosimilars are listed yet for this biologic. It currently has no biosimilar competition in the FDA Purple Book.
Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.
Patents & exclusivity — FDA Purple Book
Exclusivity RefProduct
2014 2016 2018 2020 2022 2024 2026
Today
LOE
Biologic patent Exclusivity
🏛️Reference-product exclusivity
A flat 12 years of FDA market protection from first licensure. No biosimilar can be licensed before it ends — regardless of patents.
🧪Listed biologic patents
Patents the reference maker lists covering the molecule, formulation, or manufacturing. A biosimilar generally can’t launch until these resolve.
🔁Interchangeability
An interchangeable biosimilar may be substituted at the pharmacy (state laws vary). The first one can earn its own exclusivity period.
🛈 What do these terms mean?
Biologic patent
A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
Reference-product exclusivity
A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
Interchangeable exclusivity
The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
Earliest biosimilar (LOE)
The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.

Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.

FDA exclusivity
CodeWhat it grantsExpires
RefProductReference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this dateFeb 24, 2026
Common questions
Is there a biosimilar for MYALEPT 11.3 MG (5 MG/ML) VIAL?
No FDA-licensed biosimilar is currently listed for this biologic in the FDA Purple Book.
Why do different websites show different biosimilar dates?
Biosimilar availability isn’t based on one single date. Some sources use the reference-product exclusivity, some use the last listed patent, and patent litigation, settlements, and licenses can all change the real-world launch date. This page shows the underlying Purple Book dates so you can see why estimates differ.
Can a biosimilar launch before the last patent expires?
Sometimes. A biosimilar maker may settle with the reference manufacturer or receive a license to launch earlier. In other cases, the last listed protection delays competition.
What does “current Purple Book estimate” mean?
It means we’re using the latest patent and exclusivity dates currently listed in the FDA Purple Book. It is not a guaranteed launch date.
What does “FDA listed” mean?
It means the product appears in the FDA’s official directory. That’s a good sign a product exists for the U.S. market, but on its own it does not confirm a pharmacy can get it today. Where we have recent retail pricing data, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Purple Book for a patent or exclusivity on the reference biologic. It can affect when a biosimilar becomes widely available — but it is not a guaranteed launch date. Settlements and licenses can move the real date earlier or later.
Built from the FDA Purple Book Patent List (patents the reference-product sponsor has publicly listed under the BPCIA) plus reference-product exclusivity. Biosimilars cannot launch until these clear; patent litigation and settlements can shift the real date. Biologics have no small-molecule generics — competition comes from FDA-licensed biosimilars, not the Orange Book.
Where does this data come from?
Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar launch timing is an estimate, not a guarantee.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 10122-0210-02, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q2 2025 – Q1 2026 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
88
Units reimbursed last 4 qtrs
1.3K
Gross reimbursed last 4 qtrs
$8.31M
Avg / prescription
$94,487.21
Avg / unit
$6,455.65
Latest quarter Q1 2026
29Rx
Fee-for-service vs managed care
88% FFS 12% MCO
Fee-for-service · 77 Rx Managed care · 11 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: 792 units · 7.9 per 100k residents MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: 236 units · 1.9 per 100k residents IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 260 units · 0.7 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
0.77.9
gray = no data reported
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Michigan 7.9 /100k
2 Illinois 1.9 /100k
3 California 0.7 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Myalept — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Myalept. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$7.73M
Claims incl. refills
55
Beneficiaries
24
Spend / beneficiary
$322,258.12
Spend / claim
$140,621.72
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.
🛡
This drug has a REMS — MYALEPT REMS. A Risk Evaluation & Mitigation Strategy is an FDA-required safety program. It is available only through a restricted program (certified prescribers/pharmacies, enrollment, or required monitoring). See the boxed warning & full label below, and REMS@FDA ↗.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Metreleptin — the ingredient across all brands.

Top reported reactions

Therapy Cessation92
Weight Decreased92
Blood Glucose Increased82
Therapy Interrupted66
Nausea59
Blood Triglycerides Increased53
Treatment Noncompliance52

Reporter sex

0 reports
Male · 19%
Female · 81%

Serious outcomes

Death69
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 203 70
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
10122-0210-02 You're viewing this 1 VIAL, GLASS in 1 CARTON (10122-210-02) / 2.2 mL in 1 VIAL, GLASS 2015-03-05 Active

🧭 About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 10122-210-02, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 10122-0210-02, written without dashes as 10122021002. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 10122-0210-02, the first segment (10122) is the labeler code FDA assigned to Chiesi USA, Inc.; the middle segment (0210) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (02) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Chiesi USA, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Chiesi USA, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning ~2 min read

WARNING: RISK OF ANTI-METRELEPTIN ANTIBODIES WITH NEUTRALIZING ACTIVITY AND RISK OF LYMPHOMA Anti-metreleptin antibodies with neutralizing activity have been identified in patients treated with MYALEPT. The consequences of these neutralizing antibodies are not well characterized but could include inhibition of endogenous leptin action and/or loss of MYALEPT efficacy. Severe infection and/or worsening metabolic control have been reported.

Test for anti-metreleptin antibodies with neutralizing activity in patients who develop severe infections or show signs suspicious for loss of MYALEPT efficacy during treatment. Contact Chiesi Farmaceutici S.p.A. at 1-866-216-1526 for neutralizing antibody testing of clinical samples [see Contraindications (4.1) and Warnings and Precautions (5.1) ]. T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with MYALEPT.

Carefully consider the benefits and risks of treatment with MYALEPT in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy [see Warnings and Precautions (5.2) ]. Because of these risks associated with the development of anti-metreleptin antibodies that neutralize endogenous leptin and/or MYALEPT and the risk for lymphoma, MYALEPT is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the MYALEPT REMS PROGRAM [see Warnings and Precautions (5.3) ].

WARNING: RISK OF ANTI-METRELEPTIN ANTIBODIES WITH NEUTRALIZING ACTIVITY AND RISK OF LYMPHOMA See full prescribing information for complete boxed warning. Anti-metreleptin antibodies with neutralizing activity have been identified in patients treated with MYALEPT. The consequences are not well characterized but could include inhibition of endogenous leptin action and loss of MYALEPT efficacy.

Worsening metabolic control and/or severe infection have been reported. Test for anti-metreleptin antibodies with neutralizing activity in patients with severe infections or loss of efficacy during MYALEPT treatment. Contact Chiesi Farmaceutici S.p.A. at 1-866-216-1526 for neutralizing antibody testing.

( 4.1 ), ( 5.1 ) T-cell lymphoma has been reported in patients with acquired generalized lipodystrophy, both treated and not treated with MYALEPT. Carefully consider the benefits and risks of treatment with MYALEPT in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy. ( 5.2 ) MYALEPT is available only through a restricted program called the MYALEPT REMS PROGRAM.

( 5.3 )

🎯 Indications and Usage ~1 min read

1 INDICATIONS AND USAGE MYALEPT is a leptin analog indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. ( 1 ) Limitations of Use The safety and effectiveness of MYALEPT for the treatment of complications of partial lipodystrophy have not been established. ( 1 ) The safety and effectiveness of MYALEPT for the treatment of liver disease, including nonalcoholic steatohepatitis (NASH), have not been established.

( 1 ) MYALEPT is not indicated for use in patients with HIV-related lipodystrophy. ( 1 ) MYALEPT is not indicated for use in patients with metabolic disease, without concurrent evidence of generalized lipodystrophy. ( 1 )

1.1Patients with Generalized Lipodystrophy MYALEPT (metreleptin) for injection is indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. Limitations of Use The safety and effectiveness of MYALEPT for the treatment of complications of partial lipodystrophy have not been established. The safety and effectiveness of MYALEPT for the treatment of liver disease, including nonalcoholic steatohepatitis (NASH), have not been established.

MYALEPT is not indicated for use in patients with HIV-related lipodystrophy. MYALEPT is not indicated for use in patients with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without concurrent evidence of congenital or acquired generalized lipodystrophy.

⏱️ Dosage and Administration ~3 min read

2 DOSAGE AND ADMINISTRATION Administer as a subcutaneous injection once daily after the lyophilized cake is reconstituted with Bacteriostatic Water for Injection (BWFI) or preservative-free sterile Water for Injection (WFI). ( 2.1 ) The recommended daily dosages are: Body weight 40 kg or less: starting dose 0.06 mg/kg/day, increase or decrease by 0.02 mg/kg to a maximum daily dose of 0.13 mg/kg. ( 2.1 ) Males greater than 40 kg body weight: starting dose 2.5 mg/day, increase or decrease by 1.25 mg to 2.5 mg/day to a maximum dose of 10 mg/day.

( 2.1 ) Females greater than 40 kg body weight: starting dose 5 mg/day, increase or decrease by 1.25 mg to 2.5 mg/day to a maximum dose of 10 mg/day. ( 2.1 )

2.1Recommended Dosing See Table 1 for the recommended daily dose and maximum recommended daily dose in adults and pediatric patients. Based on clinical response (e.g., inadequate metabolic control) or other considerations (e.g., tolerability issues, excessive weight loss [especially in pediatric patients]), MYALEPT dosage may be decreased or increased to the maximum dosage listed in Table 1. Table 1: MYALEPT Recommended Dosage Baseline weight Starting daily dose (injection volume) Dose adjustments (injection volume) Maximum daily dose (injection volume) Less than or equal to 40 kg (males and females) 0.06 mg/kg (0.012 mL/kg) 0.02 mg/kg (0.004 mL/kg) 0.13 mg/kg (0.026 mL/kg) Males greater than 40 kg 2.5 mg (0.5 mL) 1.25 mg (0.25 mL) to 2.5 mg (0.5 mL) 10 mg (2 mL) Females greater than 40 kg 5 mg (1 mL) 1.25 mg (0.25 mL) to 2.5 mg (0.5 mL) 10 mg (2 mL) In pediatric patients, small volumes for administration can result in medication errors when measured incorrectly [see Dosage and Administration (2.3) , Adverse Reactions (6.3) ] .

Table 2 provides example doses and volumes by weight . For patients using insulin syringes, the volume conversion is 100 Units/mL. Table 2: Example Dosing Chart for Patients Less than or Equal to 40 kg Weight Starting Dose Dose Adjustment Maximum Dose 5 kg 0.30 mg (0.06 mL or 6 Units) 0.10 mg (0.02 mL or 2 Units) 0.65 mg (0.13 mL or 13 Units) 10 kg 0.60 mg (0.12 mL or 12 Units) 0.20 mg (0.04 mL or 4 Units) 1.3 mg (0.26 mL or 26 Units) 15 kg 0.90 mg (0.18 mL or 18 Units) 0.30 mg (0.06 mL or 6 Units) 1.95 mg (0.39 mL or 39 Units) 20 kg 1.2 mg (0.24 mL or 24 Units) 0.40 mg (0.08 mL or 8 Units) 2.6 mg (0.52 mL or 52 Units) 25 kg 1.5 mg (0.3 mL or 30 Units) 0.50 mg (0.1 mL or 10 Units) 3.25 mg (0.65 mL or 65 Units) 30 kg 1.8 mg (0.36 mL or 36 Units) 0.60 mg (0.12 mL or 12 Units) 3.9 mg (0.78 mL or 78 Units) 35 kg 2.1 mg (0.42 mL or 42 Units) 0.70 mg (0.14 mL or 14 Units) 4.55 mg (0.91 mL or 91 Units) 40 kg 2.4 mg (0.48 mL or 48 Units) 0.80 mg (0.16 mL or 16 Units) 5.2 mg (1.03 mL or 103 Units) MYALEPT should be administered once daily at the same time every day.

MYALEPT can be administered any time of day without regard to the timing of meals. Instruct patients that if a dose is missed, administer the dose as soon as noticed, and resume the normal dosing schedule the next day.

2.2MYALEPT Preparation and Storage Healthcare practitioners should provide proper training to patients and caregivers regarding how to prepare and administer the correct dose of MYALEPT prior to self-use. The patients and caregivers should prepare and administer the first dose of MYALEPT under the supervision of a qualified healthcare professional. Instruct patients to store the vials of lyophilized powder in their carton in the refrigerator as soon as received [see How Supplied/Storage and Handling (16.2) ].

MYALEPT can be reconstituted aseptically with 2.2 mL of sterile Bacteriostatic Water for Injection (BWFI), USP (0.9% benzyl alcohol), or with 2.2 mL of sterile Water for Injection (WFI). When reconstituted in BWFI, MYALEPT solution can be used within 3 days when stored in the refrigerator between 36°F and 46°F (2°C and 8°C) and protected from light [see How Supplied/Storage and Handling (16.2) ]. Discard unused reconstituted solution a…

💊 Dosage Forms and Strengths 72 words

3 DOSAGE FORMS AND STRENGTHS For Injection: 11.3 mg of metreleptin supplied in a vial as a sterile, white, solid, lyophilized cake (delivers 5 mg per mL of metreleptin when reconstituted with 2.2 mL of BWFI or WFI). MYALEPT is supplied as a sterile, white, solid, lyophilized cake of 11.3 mg metreleptin per vial to deliver 5 mg per mL when reconstituted in 2.2 mL of BWFI or WFI. ( 3 )

Contraindications 109 words

4 CONTRAINDICATIONS General obesity not associated with congenital leptin deficiency. ( 4.1 ) Hypersensitivity to metreleptin. ( 4.2 )

4.1General Obesity MYALEPT is contraindicated in patients with general obesity not associated with congenital leptin deficiency. MYALEPT has not been shown to be effective in treating general obesity, and the development of anti-metreleptin antibodies with neutralizing activity has been reported in obese patients treated with MYALEPT [see Warnings and Precautions (5.1) ].

4.2Hypersensitivity MYALEPT is contraindicated in patients with prior severe hypersensitivity reactions to metreleptin or to any of the product components. Known hypersensitivity reactions have included anaphylaxis, urticaria and generalized rash [see Warnings and Precautions (5.6) ].

⚠️ Warnings and Cautions ~2 min read

5 WARNINGS AND PRECAUTIONS Anti-metreleptin antibodies with neutralizing activity: Could inhibit endogenous leptin action and/or result in loss of MYALEPT efficacy. Test for neutralizing antibodies in patients with severe infections or loss of efficacy during MYALEPT treatment. ( 5.1 ) T-cell lymphoma: Carefully consider benefits and risks of treatment with MYALEPT in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy.

( 5.2 ) Hypoglycemia: A dose adjustment, including possible large reductions, of insulin or insulin secretagogue may be necessary. Closely monitor blood glucose in patients on concomitant insulin or insulin secretagogue therapy. ( 5.4 ) Autoimmunity: Autoimmune disorder progression has been observed in patients treated with MYALEPT.

Carefully consider benefits and risks of MYALEPT treatment in patients with autoimmune disease. ( 5.5 ) Hypersensitivity: Hypersensitivity reactions (e.g., anaphylaxis, urticaria or generalized rash) have been reported. Patient should promptly seek medical advice regarding suspected reactions.

( 5.6 ) Benzyl Alcohol Toxicity: Preservative-free sterile WFI recommended for neonates and infants. ( 5.7 )

5.1Risk for Development of Antibodies that Neutralize Endogenous Leptin and/or MYALEPT Anti-metreleptin antibodies with in vitro neutralizing activity to leptin associated with adverse events consistent with loss of endogenous leptin activity and/or loss of efficacy have been identified in two patients with generalized lipodystrophy treated with MYALEPT (severe infections, increases in HbA 1c and triglycerides), and in three patients without lipodystrophy who received MYALEPT in clinical studies (excessive weight gain, development of glucose intolerance or diabetes mellitus).

The clinical implications associated with development of anti-metreleptin antibodies with neutralizing activity are not well characterized at this time due to the small number of reports. Test for anti-metreleptin antibodies with neutralizing activity in patients who develop severe infections or show signs suspicious for loss of MYALEPT efficacy during treatment. Contact Chiesi Farmaceutici S.p.A. at 1-866-216-1526 for neutralizing antibody testing of clinical samples [see Adverse Reactions (6.2) ].

5.2Lymphoma Three cases of T-cell lymphoma have been reported in the MYALEPT lipodystrophy program; all three patients had acquired generalized lipodystrophy. Two of these patients were diagnosed with peripheral T-cell lymphoma while receiving MYALEPT. Both had immunodeficiency and significant hematologic abnormalities including severe bone marrow abnormalities before the start of MYALEPT treatment.

A separate case of anaplastic large cell lymphoma was reported in a patient receiving MYALEPT who did not have hematological abnormalities before treatment. Lymphoproliferative disorders, including lymphomas, have been reported in patients with acquired generalized lipodystrophy not treated with MYALEPT. A causal relationship between MYALEPT treatment and the development and/or progression of lymphoma has not been established.

Acquired lipodystrophies are associated with autoimmune disorders, and autoimmune disorders are associated with an increased risk of malignancies including lymphomas. The benefits and risks of MYALEPT treatment should be carefully considered in patients with acquired generalized lipodystrophy and/or those with significant hematologic abnormalities (including leukopenia, neutropenia, bone marrow abnormalities, lymphoma, and/or lymphadenopathy).

5.3MYALEPT REMS Program MYALEPT is available only through a restricted distribution program under a REMS, called the MYALEPT REMS Program, because of the risks associated with the development of anti-metreleptin antibodies that neutralize endogenous leptin and/or MYALEPT and the risk for lymphoma [see Warnings and Precautions (5.1, 5.2) ]. Notable requirements of the MYALEPT REMS Program include the following: Prescrib…

🤒 Adverse Reactions ~3 min read

6 ADVERSE REACTIONS Most common in clinical trials (≥10%): headache, hypoglycemia, decreased weight, abdominal pain. ( 5.4 , 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Chiesi Farmaceutici S.p.A. at 1-888-661-9260 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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. Open-Label, Single-Arm Study The safety of MYALEPT was evaluated in 48 patients with generalized lipodystrophy in a single-arm, open-label study [see Clinical Studies (14.1) ]. The median duration of exposure in this trial was 2.7 years with a range of 3.6 months to 10.9 years.

The most frequent adverse reactions are summarized in Table 3. Table 3: Adverse Reactions of 5% or Greater Incidence in Patients with Generalized Lipodystrophy Receiving MYALEPT in an Open-Label, Single-Arm Study All Subjects N=48 (%) 1. Hypoglycemic events were assessed as mild, moderate, severe, or life threatening based on the protocol specified definitions: Mild: Documentation of low plasma glucose values with no symptoms; Moderate: Presence of clinical symptoms requiring ingestion of glucose, self-alleviated; Severe: Presence of neuroglycopenic symptoms requiring assistance from others for alleviation; Life threatening: Loss of consciousness and/or requiring intervention by administration of intravenous glucose or intramuscular glucagon.

Headache 6 (13) Hypoglycemia 1 6 (13) Decreased weight 6 (13) Abdominal pain 5 (10) Arthralgia 4 (8) Dizziness 4 (8) Ear infection 4 (8) Fatigue 4 (8) Nausea 4 (8) Ovarian cyst 4 (8) Upper respiratory tract infection 4 (8) Anemia 3 (6) Back pain 3 (6) Diarrhea 3 (6) Paresthesia 3 (6) Proteinuria 3 (6) Pyrexia 3 (6) In patients with generalized lipodystrophy receiving MYALEPT in this study, less common adverse reactions included injection-site erythema and urticaria (N=2 [4%]). Six patients (13%) had 7 adverse reactions of hypoglycemia, 6 of which occurred in the setting of concomitant insulin use, with or without oral antihyperglycemic agents.

Two patients (4%) had events of pancreatitis, both of whom had a medical history of pancreatitis.

6.2Immunogenicity As with all therapeutic proteins, there is potential for immunogenicity. Anti-metreleptin antibodies were detected in 84% (36/43) of generalized lipodystrophy patients studied in the MYALEPT trials. Total anti-metreleptin antibody titers ranged between 1:5 and 1:1,953,125.

The incompleteness of the current immunogenicity database precludes understanding of the magnitude and persistence of the observed anti-drug antibody responses. Anti-metreleptin antibodies with neutralizing activity associated with adverse events consistent with loss of endogenous leptin activity and/or loss of MYALEPT efficacy were observed in 6% (2/33) of the patients with generalized lipodystrophy tested. Adverse events reported in these two patients included severe infections and worsening of metabolic control (increases in HbA 1c and/or triglycerides).

Test for anti-metreleptin antibodies with neutralizing activity in patients who develop severe infections or show signs suspicious for loss of MYALEPT efficacy during treatment. Contact Chiesi Farmaceutici S.p.A. at 1-866-216-1526 for testing of clinical samples. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.

The immunogenicity assays utilized in clinical trials lacked sensitivity, resulting in potential underestimation of the number of samples positive for anti-metreleptin antibodies with neutralizing activity. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection,…

🔄 Drug Interactions 116 words

7 DRUG INTERACTIONS No formal drug interaction studies were performed. Leptin is a cytokine and may have the potential to alter the formation of cytochrome P450 (CYP450) enzymes. This should be taken into account when prescribing concomitant drugs metabolized by CYP450 (e.g., oral contraceptives and drugs with a narrow therapeutic index).

The effect of metreleptin on CYP450 enzymes may be clinically relevant for CYP450 substrates with narrow therapeutic index, where the dose is individually adjusted. Upon initiation or discontinuation of MYALEPT, in patients being treated with these types of agents, therapeutic monitoring of effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) should be performed and the individual dose of the agent adjusted as needed.

👥 Use in Specific Populations ~3 min read

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Pregnancy Exposure Registry There is a program that monitors outcomes in women exposed to MYALEPT during pregnancy. Women who become pregnant during MYALEPT treatment are encouraged to enroll. Patients or their physicians should call 1-855-669-2537 to enroll.

Risk Summary Available pharmacovigilance reports with the use of MYALEPT in pregnant women are insufficient to evaluate for any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. These reports describe similar adverse pregnancy outcomes as those documented in women with lipodystrophy (see Clinical Considerations ) . In an animal reproduction study, no adverse developmental effects were observed with subcutaneous administration of metreleptin to pregnant mice during organogenesis at doses 7- and 15-fold the maximum recommended clinical dose, based on body surface area of a 20- and 60-kg patient, respectively.

In a pre- and postnatal development study in mice, subcutaneous administration of metreleptin caused prolonged gestation and dystocia resulting in maternal death during parturition and lower survival of offspring in the immediate postnatal period at doses starting approximately at the maximum recommended clinical dose (see Data ) . MYALEPT contains benzyl alcohol when reconstituted with BWFI. MYALEPT contains no preservative when reconstituted with WFI.

Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely. However, adverse reactions have occurred in premature neonates and low birth weight infants who received intravenously administered benzyl alcohol-containing drugs [see Warnings and Precautions (5.7) and Use in Specific Populations (8.4) ]. Therefore, if therapy with MYALEPT is needed during pregnancy, consider using preservative-free WFI when reconstituting [see Dosage and Administration (2.2) ].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-Associated Maternal and Fetal Risk Lipodystrophy in pregnancy can result in an increased rate of gestational diabetes, macrosomia, eclampsia, intrauterine growth retardation, intrauterine death, and miscarriage.

Labor and Delivery The effects of MYALEPT on labor and delivery in pregnant women are unknown. In a published in vitro study of human myometrial tissue exposed to a recombinant leptin, human uterine contractility was inhibited. In animal studies with metreleptin, prolonged gestation and dystocia were observed (see Data ) .

Data Animal Data Metreleptin administered to pregnant mice during the period of organogenesis was not teratogenic at doses ranging between 7- and 15-fold the maximum recommended clinical dose, based on body surface area of a 20- and 60-kg patient, respectively. In a pre- and postnatal development study in mice, metreleptin administered at doses of 3, 10, and 30 mg/kg (approximately 1-, 5-, and 15-fold the clinical dose for a 60-kg subject, based on body surface area) from gestation day 6 to lactation day 21 caused prolonged gestation and dystocia at all doses, starting at approximately the maximum recommended clinical dose.

Prolonged gestation resulted in the death of some females during parturition and lower survival of offspring within the immediate postnatal period. Consistent with metreleptin pharmacology, decreased maternal body weight was observed from gestation throughout lactation at all doses and resulted in reduced weight of offspring at birth, which persisted into adulthood. However, no developmental abnormalities were observed and reproductive performance of the first or second generations was not affected at any dose.

Placental transfer of metreleptin into the fetus was low…

🤰 Pregnancy ~3 min read

8.1Pregnancy Pregnancy Exposure Registry There is a program that monitors outcomes in women exposed to MYALEPT during pregnancy. Women who become pregnant during MYALEPT treatment are encouraged to enroll. Patients or their physicians should call 1-855-669-2537 to enroll.

Risk Summary Available pharmacovigilance reports with the use of MYALEPT in pregnant women are insufficient to evaluate for any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. These reports describe similar adverse pregnancy outcomes as those documented in women with lipodystrophy (see Clinical Considerations ) . In an animal reproduction study, no adverse developmental effects were observed with subcutaneous administration of metreleptin to pregnant mice during organogenesis at doses 7- and 15-fold the maximum recommended clinical dose, based on body surface area of a 20- and 60-kg patient, respectively.

In a pre- and postnatal development study in mice, subcutaneous administration of metreleptin caused prolonged gestation and dystocia resulting in maternal death during parturition and lower survival of offspring in the immediate postnatal period at doses starting approximately at the maximum recommended clinical dose (see Data ) . MYALEPT contains benzyl alcohol when reconstituted with BWFI. MYALEPT contains no preservative when reconstituted with WFI.

Because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely. However, adverse reactions have occurred in premature neonates and low birth weight infants who received intravenously administered benzyl alcohol-containing drugs [see Warnings and Precautions (5.7) and Use in Specific Populations (8.4) ]. Therefore, if therapy with MYALEPT is needed during pregnancy, consider using preservative-free WFI when reconstituting [see Dosage and Administration (2.2) ].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-Associated Maternal and Fetal Risk Lipodystrophy in pregnancy can result in an increased rate of gestational diabetes, macrosomia, eclampsia, intrauterine growth retardation, intrauterine death, and miscarriage.

Labor and Delivery The effects of MYALEPT on labor and delivery in pregnant women are unknown. In a published in vitro study of human myometrial tissue exposed to a recombinant leptin, human uterine contractility was inhibited. In animal studies with metreleptin, prolonged gestation and dystocia were observed (see Data ) .

Data Animal Data Metreleptin administered to pregnant mice during the period of organogenesis was not teratogenic at doses ranging between 7- and 15-fold the maximum recommended clinical dose, based on body surface area of a 20- and 60-kg patient, respectively. In a pre- and postnatal development study in mice, metreleptin administered at doses of 3, 10, and 30 mg/kg (approximately 1-, 5-, and 15-fold the clinical dose for a 60-kg subject, based on body surface area) from gestation day 6 to lactation day 21 caused prolonged gestation and dystocia at all doses, starting at approximately the maximum recommended clinical dose.

Prolonged gestation resulted in the death of some females during parturition and lower survival of offspring within the immediate postnatal period. Consistent with metreleptin pharmacology, decreased maternal body weight was observed from gestation throughout lactation at all doses and resulted in reduced weight of offspring at birth, which persisted into adulthood. However, no developmental abnormalities were observed and reproductive performance of the first or second generations was not affected at any dose.

Placental transfer of metreleptin into the fetus was low (approximately 1%) following…

🧒 Pediatric Use ~1 min read

8.4Pediatric Use The MYALEPT study included a total of 35 pediatric patients (73%) with an age range from 1 to 17 years [see Clinical Studies (14.1) ]. No clinically meaningful differences were observed in the efficacy and safety of MYALEPT between pediatric and adult patients. MYALEPT contains benzyl alcohol when reconstituted with BWFI.

MYALEPT contains no preservative when reconstituted with WFI. Preservative-free WFI is recommended for use in neonates and infants. The preservative benzyl alcohol has been associated with serious adverse events and death, particularly in pediatric patients.

The "gasping syndrome" (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth weight infants. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.

Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the "gasping syndrome," the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth-weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.

When reconstituted with 2.2 mL of BWFI, MYALEPT contains 1.76 mg of benzyl alcohol per mg of metreleptin or 9 mg of benzyl alcohol per mL of reconstituted product.

🧓 Geriatric Use 68 words

8.5Geriatric Use Clinical trials of MYALEPT did not include sufficient numbers of subjects aged 65 and over (n=1) to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

🆘 Overdosage 80 words

10 OVERDOSAGE In one post-marketing case, a dose miscalculation resulted in an infant being exposed to a 10-fold overdose of metreleptin for 8 months. In this case, prolonged overdose was associated with severe anorexia causing vitamin and zinc deficiencies, iron deficiency anemia, protein calorie malnutrition, and poor weight gain, which resolved following supportive treatment and dose adjustment. In the event of an overdose, patients should be monitored and appropriate supportive treatment be initiated as dictated by the patient's clinical status.

🧬 Clinical Pharmacology ~2 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Adipocytes store lipids to meet the fuel requirements of non-adipose tissues during fasting. In patients with generalized lipodystrophy, the deficiency of adipose tissue leads to hypertriglyceridemia and ectopic deposition of fat in non-adipose tissues such as liver and muscle, contributing to metabolic abnormalities including insulin resistance. Native leptin is a hormone predominantly secreted by adipose tissue that informs the central nervous system of the status of energy stores in the body.

In patients with generalized lipodystrophy, leptin deficiency, resulting from the loss of adipose tissue, contributes to excess caloric intake, which exacerbates the metabolic abnormalities. MYALEPT (metreleptin) for injection exerts its function by binding to and activating the human leptin receptor (ObR), which belongs to the Class I cytokine family of receptors that signals through the JAK/STAT transduction pathway.

12.2Pharmacodynamics Clinical studies in patients with generalized lipodystrophy suggest that MYALEPT increases insulin sensitivity and reduces food intake. Improvements in insulin sensitivity and reductions in food intake are consistent with lower HbA 1c , fasting glucose, and fasting triglyceride values that were seen in the MYALEPT clinical trial [see Clinical Studies (14) ].

12.3Pharmacokinetics There are limited data on the pharmacokinetics of metreleptin in patients with generalized lipodystrophy, and therefore, no formal exposure-response analysis has been performed. It should be noted that the leptin assay measures both endogenous leptin as well as exogenously administered metreleptin. Absorption Peak serum leptin concentration (C max ) occurred approximately 4.0 to 4.3 hours after subcutaneous administration of single doses ranging from 0.1 to 0.3 mg/kg in healthy subjects.

In a supportive trial in lipodystrophy patients, the median T max of metreleptin was 4 hours (range: 2 to 8 hours; N=5) following single-dose administration of metreleptin. Distribution In studies of healthy adult subjects, following intravenous administration of metreleptin, leptin volume of distribution was approximately 4 to 5 times plasma volume; volumes (Vz) (mean ± SD) were 370 ± 184 mL/kg, 398 ± 92 mL/kg, and 463 ± 116 mL/kg for 0.3, 1.0, and 3.0 mg/kg/day doses, respectively. Metabolism and Elimination No formal metabolism studies have been conducted with metreleptin.

Nonclinical data indicate renal clearance is the major route of metreleptin elimination, with no apparent contribution of systemic metabolism or degradation. Following single subcutaneous doses of 0.01 to 0.3 mg/mL metreleptin in healthy subjects, the half-life was 3.8 to 4.7 hours. The clearance of metreleptin is expected to be delayed in the presence of leptin antibodies [see Adverse Reactions (6.2) ].

Drug Interactions No drug interaction studies have been conducted in lipodystrophy patients [see Drug Interactions (7) ]. Specific Populations Renal Impairment No formal pharmacokinetic studies were conducted in patients with renal impairment. Nonclinical data indicate renal clearance is the major route of metreleptin elimination, with no apparent contribution of systemic metabolism or degradation.

Hence, the pharmacokinetics of metreleptin may be altered in subjects with renal impairment. Hepatic Impairment No formal pharmacokinetic studies were conducted in patients with hepatic impairment. Age, Gender, Race, Body Mass Index Specific clinical studies have not been conducted to assess the effect of age, gender, race, or body mass index on the pharmacokinetics of metreleptin in patients with generalized lipodystrophy.

🧬 Mechanism of Action 133 words

12.1Mechanism of Action Adipocytes store lipids to meet the fuel requirements of non-adipose tissues during fasting. In patients with generalized lipodystrophy, the deficiency of adipose tissue leads to hypertriglyceridemia and ectopic deposition of fat in non-adipose tissues such as liver and muscle, contributing to metabolic abnormalities including insulin resistance. Native leptin is a hormone predominantly secreted by adipose tissue that informs the central nervous system of the status of energy stores in the body.

In patients with generalized lipodystrophy, leptin deficiency, resulting from the loss of adipose tissue, contributes to excess caloric intake, which exacerbates the metabolic abnormalities. MYALEPT (metreleptin) for injection exerts its function by binding to and activating the human leptin receptor (ObR), which belongs to the Class I cytokine family of receptors that signals through the JAK/STAT transduction pathway.

📦 How Supplied / Storage and Handling ~1 min read

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied MYALEPT (metreleptin) for injection for subcutaneous administration is supplied in a single carton containing one vial for reconstitution (NDC 10122-210-02). Each vial contains 11.3 mg metreleptin (as a sterile, white, solid, lyophilized cake) to deliver 5 mg per mL of metreleptin when reconstituted with 2.2 mL of BWFI or WFI.

16.2Storage and Handling MYALEPT should be stored in the refrigerator at 36°F to 46°F (2°C to 8°C) and protected from light until preparing for use. Keep MYALEPT vials in the carton when not in use. MYALEPT should not be used past the expiration date.

Do not freeze MYALEPT. Do not use if the white lyophilized cake is discolored. Use with BWFI: when MYALEPT is reconstituted with BWFI, the vial can be used for multiple doses within 3 days when stored in the refrigerator at 36°F to 46°F (2°C to 8°C) and protected from light.

Use with WFI: when MYALEPT is reconstituted with WFI, the vial can be used for a single dose should be administered immediately. Unused reconstituted solution cannot be saved for later use and should be discarded. After reconstitution, the vials should not be frozen (below 0°C) or shaken vigorously.

If the reconstituted product is inadvertently frozen, it should be thrown away. After reconstitution, the mixture should be clear and colorless. Do not use if visible particulates are present in the solution.

Keep out of the reach of children.

📦 Storage and Handling 182 words

16.2Storage and Handling MYALEPT should be stored in the refrigerator at 36°F to 46°F (2°C to 8°C) and protected from light until preparing for use. Keep MYALEPT vials in the carton when not in use. MYALEPT should not be used past the expiration date.

Do not freeze MYALEPT. Do not use if the white lyophilized cake is discolored. Use with BWFI: when MYALEPT is reconstituted with BWFI, the vial can be used for multiple doses within 3 days when stored in the refrigerator at 36°F to 46°F (2°C to 8°C) and protected from light.

Use with WFI: when MYALEPT is reconstituted with WFI, the vial can be used for a single dose should be administered immediately. Unused reconstituted solution cannot be saved for later use and should be discarded. After reconstitution, the vials should not be frozen (below 0°C) or shaken vigorously.

If the reconstituted product is inadvertently frozen, it should be thrown away. After reconstitution, the mixture should be clear and colorless. Do not use if visible particulates are present in the solution.

Keep out of the reach of children.

📋 Description 125 words

11 DESCRIPTION MYALEPT (metreleptin) for injection is a recombinant human leptin analog for injection that binds to and activates the leptin receptor. Metreleptin (recombinant methionyl-human leptin) is produced in E. coli and differs from native human leptin by the addition of a methionine residue at its amino terminus. Metreleptin is a 147-amino acid, nonglycosylated, polypeptide with one disulfide bond between Cys-97 and Cys-147 and a molecular weight of approximately 16.15 kDa.

MYALEPT is supplied as a sterile, white, solid, lyophilized cake containing 11.3 mg that is reconstituted with 2.2 mL of BWFI or WFI to a final formulation of 5 mg/mL metreleptin for subcutaneous injection. Inactive ingredients are: glutamic acid (1.47 mg/mL), glycine (20 mg/mL), polysorbate 20 (0.1 mg/mL), and sucrose (10 mg/mL), pH 4.25.

💬 Information for Patients ~2 min read

17 PATIENT COUNSELING INFORMATION See FDA-approved Patient Labeling ( Medication Guide ). Risk of Neutralizing Antibodies Advise patients that neutralizing antibodies may result in loss in activity of endogenous leptin or loss of efficacy of MYALEPT. Advise patients on symptoms or signs that would warrant antibody testing [see Warnings and Precautions (5.1) and Adverse Reactions (6.2) ].

Risk of Lymphoma Advise patients that lymphoma has been reported in patients both treated and not treated with MYALEPT. Advise patients on symptoms or signs that indicate changes in hematologic status and the importance of routine laboratory assessments and physician monitoring [see Warnings and Precautions (5.2) ]. Risk of Hypoglycemia Advise patients that the risk of hypoglycemia is increased when MYALEPT is used in combination with insulin or an insulin secretagogue (e.g., sulfonylurea).

Explain the symptoms, treatment, and conditions that predispose to development of hypoglycemia to the patient. Advise patients who are taking concomitant insulin, especially those on high doses, or an insulin secretagogue, to closely monitor blood glucose. Hypoglycemia management should be reviewed and reinforced when initiating MYALEPT therapy, particularly when concomitantly administered with insulin or an insulin secretagogue [see Warnings and Precautions (5.4) ].

Risk of Autoimmune Disease Advise patients that worsening of autoimmune disease has been reported during the clinical study of MYALEPT. Advise patients with a history of autoimmune disease on symptoms or signs that indicate exacerbation of underlying autoimmune disease and the importance of routine laboratory assessments and physician monitoring [see Warnings and Precautions (5.5) ]. Risk of Hypersensitivity Reactions Inform patients that hypersensitivity reactions have been reported during use of MYALEPT.

If symptoms of hypersensitivity reactions occur, patients should seek medical advice [see Warnings and Precautions (5.6) ]. Instructions Inform patients that each vial of MYALEPT requires reconstitution with BWFI or preservative-free WFI, and administration as subcutaneous injection using a syringe and needle. Injections can be given at any time of the day, with or without meals.

Patients and caregivers should receive proper training in how to prepare and administer the correct dose of MYALEPT prior to self-administration. The first dose of MYALEPT should be administered by the patient or caregiver under the supervision of a qualified healthcare professional. Advise patients on appropriate syringe for administration, dosing regimen, injection technique, and the importance of proper storage of MYALEPT.

Care should be taken to avoid intramuscular injection, especially in patients with minimal subcutaneous adipose tissue. Advise patients to read the Instructions for Use for complete administration instructions. The MYALEPT Medication Guide and Instructions for Use should be reviewed before starting therapy and each time the prescription is refilled.

When discontinuing MYALEPT in patients with a history of pancreatitis and/or severe hypertriglyceridemia, instruct patients to taper their dose over a one-week period. Advise patients that additional monitoring of triglyceride levels and possible initiation or dose adjustment of lipid-lowering medications may be considered [see Dosage and Administration (2.5) ].

💬 Medication Guide ~3 min read

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised 03/2024 MYALEPT ® (MAI-uh-lept) (metreleptin) for injection, for subcutaneous use What is the most important information I should know about MYALEPT?

MYALEPT may cause serious side effects, including: risk for loss of endogenous leptin activity or loss of MYALEPT efficacy due to neutralizing antibodies. Some people who use MYALEPT make antibodies in their blood that may reduce how well the leptin in your body (endogenous) works or how well MYALEPT works. Side effects may include: infection problems with blood sugar, including diabetes an increase in the amount of fat in your blood (triglycerides) lymphoma (a type of blood cancer).

There may be an increased risk of getting lymphoma when you use MYALEPT. MYALEPT is only available through a restricted program called the MYALEPT Risk Evaluation and Mitigation Strategy (REMS) Program. For more information about the MYALEPT REMS Program go to www.myaleptrems.com or call 1-855-669-2537.

What is MYALEPT? MYALEPT is a prescription medicine used with a diet recommended by your healthcare provider to treat problems caused by not having enough leptin in your body (leptin deficiency) in people with congenital or acquired generalized lipodystrophy. It is not known if MYALEPT is safe and effective when used: to treat problems (complications) caused by partial lipodystrophy to treat liver disease, including non-alcoholic steatohepatitis (NASH) MYALEPT should not be used to treat: people with HIV-related lipodystrophy people with metabolic disease, including diabetes mellitus and hypertriglyceridemia, without signs or symptoms of congenital or acquired generalized lipodystrophy Do not use MYALEPT if you: have general obesity that is not caused by a congenital leptin deficiency. are allergic to metreleptin or any of the ingredients in MYALEPT.

See the end of this Medication Guide for a complete list of ingredients in MYALEPT. Talk to your healthcare provider right away if you have any symptoms of an allergic reaction including a rash or itching (hives). Symptoms of a severe allergic reaction may include: swelling of your face, lips, tongue, or throat problems breathing or swallowing severe rash or itching fainting or feeling dizzy very rapid heartbeat What should I tell my healthcare provider before using MYALEPT?

Before using MYALEPT, tell your healthcare provider if you: have or have had problems with your blood cells including low blood cell counts, especially white blood cells have or have had problems with your bone marrow have or have had swollen lymph nodes (lymphadenopathy) have or have had lymphoma use insulin or a sulfonylurea have or have had problems with your immune system (autoimmune disease) have or have had problems with your pancreas (pancreatitis) have high blood triglyceride levels have any other medical conditions are pregnant or plan to become pregnant.

It is not known if MYALEPT will harm your unborn baby If you become pregnant while using MYALEPT, talk to your healthcare provider about registering with a program to collect information about the outcomes of moms and babies exposed to MYALEPT during pregnancy. You can enroll in the MYALEPT program by calling 1-855-669-2537. are breastfeeding or plan to breastfeed. It is not known if MYALEPT passes into your breastmilk.

Talk to your healthcare provider about the best way to feed your baby while taking MYALEPT. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Know the medicines you take.

Keep a list of them with you to show your healthcare provider and pharmacist when you get a new medicine. How should I use MYALEPT? See the Instructions for Use that come with MYALEPT for detailed instructions on using MYALEPT the right way.

Use MYALEPT exactly as your healthcare provider tells you to. Your healthcare provider will tell you how much MY…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.