Lemtrada

Mechanism of Action

Recombinant monoclonal antibody against CD52 (lymphocyte antigen); promotes antibody-dependent lysis

Pharmacokinetics

Half-Life: 12 days

Vd: 14.1 L; largely confined to blood and interstitial space

Metabolism: unknown

Excretion: unknown

The following serious adverse reactions are described below and elsewhere in the labeling:

• Autoimmunity [see BOXED WARNINGand WARNINGS AND PRECAUTIONS]
• Infusion reactions [see BOXED WARNING and WARNINGS AND PRECAUTIONS]
• Malignancies [see WARNINGS AND PRECAUTIONS]
• Immune Thrombocytopenia [see WARNINGS AND PRECAUTIONS]
• Glomerular Nephropathies [see WARNINGS AND PRECAUTIONS]
• Thyroid Disorder [see WARNINGS AND PRECAUTIONS]
• Other Autoimmune Cytopenias [see WARNINGS AND PRECAUTIONS]
• Infections [see WARNINGS AND PRECAUTIONS]
• Pneumonitis [see WARNINGS AND PRECAUTIONS]

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.

In controlled clinical trials (Study 1 and Study 2), a total of 811 patients with relapsing forms of MS received LEMTRADA. A total of 811 patients received 1 course of therapy, and 789 patients received a second course of therapy at 12 months. The overall follow-up in the controlled trials was equivalent to 1622 patient years, with an additional 3411 person-years of follow-up in an open label extension study. The population was 1855 years of age, 65% were female, and 92% were Caucasian.

Most Common Adverse Reactions

In clinical trials, the most common adverse reactions with LEMTRADA (in at least 10% of patients and more frequently than in interferon beta-1a) were rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting.

Table 1 lists adverse reactions occurring in ≥ 5% of LEMTRADA-treated patients in Study 1 and 2 and at the same or at a higher rate than interferon beta-1a.

Table 1: Adverse Reactions in the Pooled 2-Year Active-Controlled Studies in Patients with Relapsing-Remitting Multiple Sclerosis

	LEMTRADA (N=811) %	interferon beta-1a 44 mcg (N=389) %
Rash	53	6
Headache	52	23
Pyrexia	29	9
Nasopharyngitis	25	19
Nausea	21	9
Urinary tract infection	19	8
Fatigue	18	13
Insomnia.	16	15
Upper respiratory tract infection	16	13
Herpes viral infection	16	3
Urticaria	16	2
Pruritus	14	2
Thyroid gland disorders	13	3
Fungal infection	13	4
Arthralgia	12	9
Pain in extremity	12	9
Back pain	12	8
Diarrhea	12	6
Sinusitis	11	8
Oropharyngeal pain	11	5
Paresthesia	10	8
Dizziness	10	5
Abdominal pain	10	5
Flushing	10	4
Vomiting	10	3
Cough	9	4
Chills	9	3
Dysgeusia	8	7
Influenza	8	6
Dermatitis	8	5
Dyspepsia	8	4
Blood in urine	8	3
Dyspnea	8	1
Tachycardia	8	1
Anxiety	7	6
Muscular weakness	7	6
Bronchitis	7	4
Chest discomfort	7	2
Muscle spasms	6	5
Myalgia	6	5
Decrease in CD4 lymphocytes	6	2
Decrease in CD8 lymphocytes	6	2
Asthenia	5	4
Decrease in T-lymphocyte count	5	3
Erythema	5	2
Peripheral edema	5	2
Epistaxis	5	2
Neck Pain	5	2
Abnormal uterine bleeding	5	1

Lymphopenia

Nearly all (99.9%) patients treated with LEMTRADA in MS clinical trials experienced lymphopenia. The lowest lymphocyte counts occurred approximately by 1 month after each course of treatment. The mean lymphocyte count at 1 month after LEMTRADA treatment was 0.25 x 109L (range 0.02-2.30 x 109L) and 0.32 (0.02-1.81 x 109L) for treatment courses 1 and 2, respectively. Total lymphocyte counts increased to reach the lower limit of normal in approximately 40% of patients by 6 months after each LEMTRADA treatment course and approximately 80% of patients by 12 months after each course [see CLINICAL PHARMACOLOGY].

Suicidal Behavior Or Ideation

In clinical studies, 0.6% of patients in both the LEMTRADA and interferon beta-1a groups had events of attempted suicide or suicidal ideation. There were no completed suicides in either clinical study treatment group. Suicidal behavior or ideation occurred in patients with or without a history of a psychiatric or thyroid disorder. Advise patients to report immediately any symptoms of depression or suicidal ideation to the prescribing physician.

Immunogenicity

As with all therapeutic proteins, there is potential for immunogenicity. Using an enzymelinked immunosorbent assay (ELISA) and a competitive binding assay, anti-alemtuzumab binding antibodies were detected in 62%, 67%, and 29% of LEMTRADA-treated patients, at months 1, 3, 12 (Course 1) as well as 83%, 83%, and 75% of LEMTRADAtreated patients at months 13, 15, and 24 (Course 2). Samples that tested positive for binding antibodies were further evaluated for evidence of in vitro inhibition using a flow cytometry assay. Neutralizing antibodies were detected in 87%, 46%, and 5% of positive binding antibody patients at months 1, 3, 12 (Course 1) as well as 94%, 88%, and 42% of positive binding antibody patients at months 13, 15, and 24 (Course 2). Antialemtuzumab antibodies were associated with decreased alemtuzumab concentration during Course 2 but not Course 1. There was no evidence from clinical trials that the presence of binding or inhibitory anti-alemtuzumab antibodies had a significant effect on clinical outcomes, total lymphocyte count, or adverse events.

The incidence of antibodies is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including inhibitory antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to LEMTRADA with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions, not described elsewhere, were identified during postapproval use of alemtuzumab (CAMPATH) for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), as well as for the treatment of other disorders, generally at higher and more frequent doses (e.g., 30 mg) than that recommended in the treatment of MS. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Cardiac Disorders

Congestive heart failure, cardiomyopathy, and decreased ejection fraction in non-MS patients previously treated with potentially cardiotoxic agents.

Read the entire FDA prescribing information for Lemtrada (Alemtuzumab Injection for Intravenous Infusion)

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• Genzyme Corporation

Alemtuzumab is an antibody made from animal DNA.

Alemtuzumab is used to treat chronic B-cell lymphocytic leukemia or relapsing forms of multiple sclerosis.

Lemtrada is available only from a certified pharmacy under a special program. You must be registered in the program and understand the risks of taking this medicine.

Alemtuzumab may also be used for purposes not listed in this medication guide.

You should not receive alemtuzumab if you are allergic to it. You should not be treated with Lemtrada if you have HIV (human immunodeficiency virus).

To make sure alemtuzumab is safe for you, tell your doctor if you have any of these other conditions:

• an active or recent infection;

• kidney disease;

• a thyroid disorder;

• a bleeding or blood clotting disorder such as hemophilia; or

• if you have received a vaccine in the past 6 weeks.

Using alemtuzumab may increase your risk of developing other types of cancer, such as melanoma, thyroid cancer, or blood cancers. Ask your doctor about your specific risk.

It is not known whether alemtuzumab will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. Use effective birth control to prevent pregnancy while you are receiving alemtuzumab, and for at least 4 months after each course of treatment.

It is not known whether alemtuzumab passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Call your doctor for instructions if you miss an appointment for your alemtuzumab injection.

• It is used to treat MS (multiple sclerosis).
• It may be given to you for other reasons. Talk with the doctor.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies to assess the carcinogenic or genotoxic potential of Lemtrada have not been conducted.

When Lemtrada (3 or 10 mg/kg IV) was administered to huCD52 transgenic male mice on 5 consecutive days prior to cohabitation with untreated wild-type females, no effect on fertility or reproductive performance was observed. However, adverse effects on sperm parameters (including abnormal morphology [detached /no head] and reduced total count and motility) were observed at both doses tested.

When Lemtrada (3 or 10 mg/kg IV) was administered to huCD52 transgenic female mice for 5 consecutive days prior to cohabitation with untreated wild-type males, there was a decrease in the average number of corpora lutea and implantation sites and an increase in post-implantation loss, resulting in fewer viable embryos at the higher dose tested.

The efficacy of Lemtrada was demonstrated in two studies (Study 1 and 2) that evaluated Lemtrada 12 mg in patients with relapsing-remitting multiple sclerosis (RRMS). Lemtrada was administered by intravenous infusion once daily over a 5-day course, followed one year later by intravenous infusion once daily over a 3-day course. Both studies included patients who had experienced at least 2 relapses during the 2 years prior to trial entry and at least 1 relapse during the year prior to trial entry. Neurological examinations were performed every 12 weeks and at the time of suspected relapse. Magnetic resonance imaging (MRI) evaluations were performed annually.

Study 1

Study 1 was a 2 year randomized, open-label, rater-blinded, active comparator (interferon beta-1a 44 micrograms administered subcutaneously three times a week) controlled study in patients with RRMS. Patients entering Study 1 had Expanded Disability Status Scale (EDSS) scores of 5 or less and had to have experienced at least one relapse while on interferon beta or glatiramer acetate therapy.

Patients were randomized to receive Lemtrada (n=426) or interferon beta-1a (n=202). At baseline, the mean age was 35 years, the mean disease duration was 4.5 years, and the mean EDSS score was 2.7.

The clinical outcome measures were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression. Confirmed disability progression was defined as at least a 1 point increase above baseline EDSS (1.5 point increase for patients with baseline EDSS of 0) sustained for 6 months. The MRI outcome measure was the change in T2 lesion volume.

The annualized relapse rate was significantly lower in patients treated with Lemtrada than in patients who received interferon beta-1a. Time to onset of 6-month confirmed disability progression was significantly delayed with Lemtrada treatment compared to interferon beta-1a. There was no significant difference between the treatment groups for the change in T2 lesion volume. The results of Study 1 are shown in Table 2 and Figure 1.

Table 2: Clinical and MRI Results of Study 1

	Lemtrada (N=426)	interferon beta-1a 44 mcg (N=202)	p-value
Clinical Outcomes
Annualized relapse rate   Relative reduction	0.26 49%	0.52	<0.0001
Proportion of patients with disability progression at Year 2   Relative risk reduction	13% 42%	21%	0.0084
Percent of patients remaining relapse-free at Year 2	65%	47%	<0.0001
MRI Outcomes
Percent change in T2 lesion volume from baseline	-1.3	-1.2	0.14

Figure 1: Time to 6-month Confirmed Disability Progression (Study 1)

Study 2

Study 2 was a 2-year randomized, open-label, rater-blinded, active comparator (interferon beta-1a 44 micrograms administered subcutaneously three times a week) controlled study in patients with RRMS. Patients entering Study 2 had EDSS scores of 3 or less and no prior treatment for multiple sclerosis.

Patients were randomized to receive Lemtrada (n=376) or interferon beta-1a (n=187). At baseline, the mean age was 33 years, the mean disease duration was 2 years, and the mean EDSS score was 2.

The clinical outcome measures were the annualized relapse rate (ARR) over 2 years and the time to confirmed disability progression, as defined in Study 1. The MRI outcome measure was the change in T2 lesion volume.

The annualized relapse rate was significantly lower in patients treated with Lemtrada than in patients who received interferon beta-1a. There was no significant difference between the treatment groups for the time to confirmed disability progression and for the primary MRI endpoint (change in T2 lesion volume). The results for Study 2 are shown in Table 3.

Table 3: Clinical and MRI Results of Study 2

	Lemtrada	interferon beta-1a 44 mcg	p-value
	(N=376)	(N=187)
Clinical Outcomes
Annualized relapse rate   Relative reduction	0.18 55%	0.39	<0.0001
Proportion of patients with disability progression at Year 2   Relative risk reduction	8% 30%	11%	0.22
Percent of patients remaining relapse-free at Year 2	78%	59%	<0.0001
MRI Outcomes
Percent change in T2 lesion volume from baseline	-9.3	-6.5	0.31

Lemtrada® (lem-TRA-da)
(alemtuzumab)
Injection for intravenous infusion

Read this Medication Guide before you start receiving Lemtrada and before you begin each treatment course. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is the most important information I should know about Lemtrada?

Lemtrada can cause serious side effects, including:

1. Serious autoimmune problems. Some people receiving Lemtrada develop a condition where the immune cells in your body attack other cells or organs in the body (autoimmunity) which can be serious and may cause death. Serious autoimmune problems may include: • immune thrombocytopenic purpura (ITP). Lemtrada may cause the number of platelets in your blood to be reduced (ITP). ITP can cause severe bleeding that, if not treated, may cause life-threatening problems. Call your healthcare provider right away if you have any of the following symptoms: ○ easy bruising ○ bleeding from a cut that is hard to stop ○ heavier menstrual periods than normal ○ bleeding from your gums or nose that is new or takes longer than usual to stop ○ small, scattered spots on your skin that are red, pink, or purple • kidney problems. Lemtrada may cause a serious kidney problem, called anti-glomerular basement membrane disease. If this happens and you do not get treated, anti-glomerular basement membrane disease can lead to severe kidney damage, kidney failure that needs dialysis, a kidney transplant, or death. Call your healthcare provider right away if you have any of the following symptoms: ○ blood in the urine (red or tea-colored urine) ○ swelling in your legs or feet ○ coughing up blood
Side effects may happen while you receive Lemtrada and for 4 years after you stop receiving Lemtrada. Your healthcare provider will order blood and urine tests before you receive, while you are receiving, and every month for 4 years after you receive your last Lemtrada infusion. You may need to continue these blood and urine tests after 4 years if you have any autoimmune signs or symptoms. The blood and urine tests will help your healthcare provider watch for signs and symptoms of serious autoimmune problems.
It is important to have your blood and urine tested, even if you are feeling well and do not have any symptoms from Lemtrada and your multiple sclerosis. This may help your healthcare provider find any problems early and will increase your chances of getting better. 2. Serious infusion reactions. Lemtrada can cause serious infusion reactions that may cause death. Serious infusion reactions may happen while you receive, or up to 24 hours or longer after you receive Lemtrada.
You will receive your infusion at a healthcare facility with equipment and staff trained to manage infusion reactions. You will be watched while you receive and for 2 hours after you receive Lemtrada. It is important that you stay at the infusion center for 2 hours after your infusion is finished or longer if your healthcare provider decides you need to stay longer. If a serious infusion reaction happens while you are receiving Lemtrada, your infusion may be stopped.
Tell your healthcare provider right away if you have any of the following symptoms of a serious infusion reaction during the infusion, and after you have left the healthcare facility: ○ swelling in your mouth or throat ○ trouble breathing ○ weakness ○ fast, slow, or irregular heart beat ○ chest pain ○ rash To lower your chances of getting a serious infusion reaction, your healthcare provider will give you a medicine called corticosteroids before your first 3 infusions of a treatment course. You may also be given other medicines before or after the infusion to try reduce your chances of these reactions or to treat them after they happen. 3. Certain cancers. Receiving Lemtrada may increase your chance of getting some kinds of cancers, including thyroid cancer, skin cancer (melanoma), and blood cancers called lymphoproliferative disorders and lymphoma. Call your healthcare provider if you have the following symptoms that may be a sign of thyroid cancer:

new lump swelling in your neck pain in the front of your neck

hoarseness or other voice changes that do not go away trouble swallowing or breathing cough that is not caused by a cold

You should have your skin checked before you start receiving Lemtrada and each year while you are receiving treatment to monitor symptoms of skin cancer.

  Because of your risk of autoimmunity, infusion reactions and the risk of some kinds of cancers, Lemtrada is only available through a restricted program called the Lemtrada Risk Evaluation and Mitigation Strategy (REMS) Program. Call 1-855-676-6326 to enroll in the Lemtrada REMS Program. • You and your healthcare provider must be enrolled in the Lemtrada REMS Program. • Lemtrada can only be given at a certified healthcare facility that participates in the Lemtrada REMS Program. Your healthcare provider can give you information on how to find a certified healthcare facility. • Read the Lemtrada REMS "What You Need to Know About Lemtrada Treatment: A Patient Guide" and "What you Need to Know About Lemtrada Treatment and Infusion Reactions: A Patient Guide" after you are enrolled in the program. • Carry your Lemtrada REMS Patient Safety Information Card with you in case of an emergency.

What is Lemtrada?

Lemtrada is a prescription medicine used to treat adults with relapsing forms of multiple sclerosis (MS). Because of its risks, Lemtrada is generally used in people who have tried 2 or more MS medicines that have not worked well enough. It is not known if Lemtrada is safe and effective for use in children under 17 years of age.

Who should not receive Lemtrada?

Do not receive Lemtrada if you are infected with human immunodeficiency virus (HIV).

What should I tell my healthcare provider before receiving Lemtrada?

Before receiving Lemtrada, tell your healthcare provider if you:

• are taking a medicine called Campath®. Alemtuzumab the active ingredient in Lemtrada is the same drug as Campath.
• have bleeding problems
• have thyroid problems
• have kidney problems
• have a recent history of infection
• have HIV
• have received a live vaccine in the past 6 weeks before receiving Lemtrada or plan to receive any live vaccines. Ask your healthcare provider if you are not sure if your vaccine is a live vaccine.
• are pregnant or plan to become pregnant. Lemtrada may harm your unborn baby. You should use birth control while receiving Lemtrada and for 4 months after your course of treatment.
• are breastfeeding or plan to breastfeed. It is not known if Lemtrada passes into your breast milk. You and your healthcare provider should decide if you should receive Lemtrada or breastfeed. You should not do both.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Lemtrada and other medicines may affect each other causing side effects. Especially tell your healthcare provider if you take medicines that increase your chance of getting infections, including medicines used to treat cancer or to control your immune system.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How will I receive Lemtrada?

• Lemtrada is given through a needle placed in your vein (IV infusion).
• It takes about 4 hours to receive a full dose of Lemtrada each day.
• You will receive Lemtrada over 2 treatment courses.
• You will receive Lemtrada for 5 days in a row (consecutive) for the first treatment course and then for 3 days in a row (consecutive) about 1 year later for your second treatment course.

What are the possible side effects of Lemtrada?

Lemtrada may cause serious side effects including:

• See "What is the most important information I should know about Lemtrada?"
• thyroid problems. Some people who receive Lemtrada may get thyroid problems including an overactive thyroid (hyperthyroidism) or an underactive thyroid (hypothyroidism). Your healthcare provider will do blood tests to check how your thyroid is working. Call your healthcare provider if you have any of the symptoms of thyroid problems.
  Symptoms of hyperthyroidism may include:

  excessive sweating unexplained weight loss eye swelling

  nervousness fast heartbeat

  Symptoms of hypothyroidism may include:

  unexplained weight gain feeling cold

  worsening tiredness constipation

• low blood counts (cytopenias). Lemtrada may cause a decrease in some types of blood cells. Some people with these low blood counts have increased infections. Symptoms of cytopenias may include:

  weakness chest pain yellowing of the skin or whites of eyes (jaundice)

  dark urine fast heartbeat

  Your healthcare provider will do blood tests to check for cytopenias. Call your healthcare provider right away if you have symptoms listed above.
• serious infections. Lemtrada may cause you to have serious infections while you receive and after receiving a treatment course. Serious infections may include:
  • herpes viral infections. Some people taking Lemtrada have an increased chance of getting herpes viral infections. Your healthcare provider will prescribe medicines to reduce your chances of getting these infections. Take these medicines exactly as your healthcare provider tells you to.
  • human papilloma virus (HPV). Females have an increased chance of getting a cervical HPV infection. If you are a female, you should have an HPV screening each year.
  • tuberculosis. Your healthcare provider should check you for tuberculosis before you receive Lemtrada.
  • fungal infections.
  • listeria. People who receive Lemtrada have an increased chance of getting an infection caused by the bacteria, listeria. Avoid foods that may be a source for listeria (for example, deli meat, unpasteurized milk and cheese products, or undercooked meat, seafood or poultry) or make sure that the food you eat which may contain listeria is heated well if you receive treatment with Lemtrada.
  Call your healthcare provider right away if you have symptoms of a serious infection, such as fever or swollen glands. You may need to go to the hospital for treatment if you get a serious infection. It is important to tell the healthcare providers that you have received Lemtrada.
  Talk to your healthcare provider before you get vaccinations after receiving Lemtrada. Certain vaccinations may increase your chances of getting infections.
• swelling of lung tissue (pneumonitis). Some people have had swelling of the lung tissue while receiving Lemtrada. Call your healthcare provider right away if you have the following symptoms:

  shortness of breath cough wheezing

  chest pain or tightness coughing up blood

The most common side effects of Lemtrada include:

rash headache thyroid problems fever swelling of your nose and throat (nasopharyngitis) nausea urinary tract infection feeling tired trouble sleeping upper respiratory tract infection herpes viral infection hives itching

fungal infection joint pain pain in your arms or legs back pain diarrhea sinus infection mouth pain or sore throat tingling sensation dizziness stomach pain sudden redness in face, neck, or chest vomiting

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Lemtrada. For more information, ask your healthcare provider or pharmacist.

Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

General information about the safe and effective use of Lemtrada.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Lemtrada for a condition for which it was not prescribed. Do not give Lemtrada to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Lemtrada. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about Lemtrada that is written for health professionals.

For more information, go to www.LemtradaREMS.com or call Genzyme at 1-855-676-6326.

What are the ingredients in Lemtrada?

Active ingredient: alemtuzumab

Inactive ingredients: sodium chloride, dibasic sodium phosphate, potassium chloride, potassium dihydrogen phosphate, polysorbate 80, disodium edetate dihydrate, and water for injection.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured and distributed by:

Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

US License Number: 1596

Lemtrada and CAMPATH are registered trademarks of Genzyme Corporation.

©2016 Genzyme Corporation. All rights reserved.

NDC 58468-0200-1

Lemtrada®
(alemtuzumab)
injection

12 mg/1.2 mL
(10 mg/mL)

For Intravenous Infusion Only
Dilute before
Intravenous Infusion
Single-Dose Vial,
Discard Unused Portion

Rx only

Dispense the enclosed
Medication Guide to each
patient.

Lemtrada  alemtuzumab injection, solution, concentrate

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:58468-0200 Route of Administration INTRAVENOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ALEMTUZUMAB (alemtuzumab) ALEMTUZUMAB 12 mg  in 1.2 mL

Inactive Ingredients Ingredient Name Strength EDETATE DISODIUM 0.0224 mg  in 1.2 mL POTASSIUM CHLORIDE 0.24 mg  in 1.2 mL POTASSIUM PHOSPHATE, MONOBASIC 0.24 mg  in 1.2 mL SODIUM CHLORIDE 9.6 mg  in 1.2 mL SODIUM PHOSPHATE, DIBASIC 1.38 mg  in 1.2 mL Polysorbate 80 0.12 mg  in 1.2 mL Water

Packaging # Item Code Package Description 1 NDC:58468-0200-1 1 VIAL, SINGLE-USE in 1 CARTON 1 2 mL in 1 VIAL, SINGLE-USE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA103948 11/18/2014

Labeler - Genzyme Corporation (025322157)

Establishment
Name	Address	ID/FEI	Operations
Boehringer Ingelheim Pharma GmbH & Co. KG (BI Pharma)		340700520	ANALYSIS(58468-0200), MANUFACTURE(58468-0200), API MANUFACTURE(58468-0200)

Establishment
Name	Address	ID/FEI	Operations
Genzyme Ireland Ltd		985127419	MANUFACTURE(58468-0200)

Establishment
Name	Address	ID/FEI	Operations
Genzyme Limited		229522842	MANUFACTURE(58468-0200)

Revised: 06/2016   Genzyme Corporation