Talimogene Laherparepvec Suspension for Intralesional Injection

IMLYGIC (talimogene laherparepvec) is a sterile suspension for intralesional injection. IMLYGIC is a live, attenuated HSV-1 that has been genetically modified to express huGM-CSF. The parental virus for IMLYGIC was a primary isolate, which was subsequently altered using recombinant methods to result in gene deletions and insertions.

Each vial contains 1 mL deliverable volume of IMLYGIC at either 1 x 106 (1 million) PFU per mL or 1 x 108 (100 million) PFU per mL concentrations and the following excipients: di-sodium hydrogen phosphate dihydrate (15.4 mg), sodium dihydrogen phosphate dihydrate (2.44 mg), sodium chloride (8.5 mg), myo-inositol (40 mg), sorbitol (20 mg), and water for injection.

The 106 (1 million) PFU per mL vial of IMLYGIC contains a clear to semi-translucent liquid following thaw from its frozen state. The 108 (100 million) PFU per mL vial of IMLYGIC contains a semitranslucent to opaque liquid following thaw from its frozen state. The liquid in each vial may contain white, visible, variously shaped, virus-containing particles.

Each vial of IMLYGIC may also contain residual components of VERO cells including DNA and protein and trace quantities of fetal bovine serum.

The product contains no preservative.

IMLYGIC is a genetically modified oncolytic viral therapy indicated for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.

Limitations Of Use

IMLYGIC has not been shown to improve overall survival or have an effect on visceral metastases.

Dosage Forms And Strengths

• Initial dose only: 106 (1 million) PFU per mL solution in 1 mL single-use vial (light green cap)
• Subsequent doses: 108 (100 million) PFU per mL solution in 1 mL single-use vial (royal blue cap)

Storage And Handling

• IMLYGIC is provided as a sterile frozen suspension in a single-use, cyclic olefin polymer (COP) plastic resin vial with a chlorobutyl elastomer stopper, aluminum seal, and polypropylene cap. Each vial contains a retrievable minimal volume of 1 mL.
• The vial cap is color coded:
  • 106 (1 million) PFU per mL is light green (NDC 55513-078-01).
  • 108 (100 million) PFU per mL is royal blue (NDC 55513-079-01).

• Store and transport IMLYGIC at .90°C to .70°C (.130°F to .94°F).
• Protect IMLYGIC from light.
• Store IMLYGIC in the carton until use.
• Thaw IMLYGIC immediately prior to administration [see DOSAGE AND ADMINISTRATION].
• Do not draw IMLYGIC into a syringe until immediately prior to administration [see DOSAGE AND ADMINISTRATION].

Manufactured by: BioVex, Inc., a subsidiary of Amgen Inc. One Amgen Center Drive Thousand Oaks, California. Revised: March 2017

IMLYGIC®
(imm-LY-jik)
(talimogene laherparepvec)

Read the Medication Guide before you start treatment with IMLYGIC and before each IMLYGIC treatment. There may be new information. This Medication Guide does not tell you everything about IMLYGIC. Talk with your healthcare provider if you have any questions about treatment with IMLYGIC.

What is IMLYGIC?

IMLYGIC is a prescription medicine used to treat a type of cancer called melanoma when it is on your skin or in your lymph glands. IMLYGIC is a weakened form of Herpes Simplex Virus Type 1, which is commonly called the cold sore virus. Your healthcare provider will inject IMLYGIC directly into your tumor(s).

IMLYGIC may not help you live longer and may not shrink cancer in your organs (for example, lung or liver).

Who should not get IMLYGIC?

You should not get IMLYGIC if you are pregnant or have a weakened immune system (for example, an immune deficiency, blood or bone marrow cancer, steroid use, or HIV/AIDS).

What should I tell my healthcare provider before I get IMLYGIC?

Before getting IMLYGIC, tell your healthcare provider if you:

• Are taking steroids or other medicines that suppress your immune system.
• Are taking antiviral medicines to treat or prevent herpes, such as acyclovir.
• Have or ever had medical conditions such as:
  • HIV infection or AIDS.
  • Blood or bone marrow cancer.
  • Autoimmune disease.
  • Other medical conditions that can weaken your immune system.
• Have close contact with someone who has a weakened immune system or is pregnant.
• Are pregnant or plan to become pregnant.
  • IMLYGIC may harm your unborn baby.
  • You should not become pregnant during treatment with IMLYGIC.
  • Talk to your healthcare provider about effective birth control methods.
• Are breastfeeding or plan to breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription and over-thecounter medicines, vitamins, and herbal supplements. IMLYGIC may affect the way other medicines work and other medicines may affect how IMLYGIC works.

How is IMLYGIC given?

Your healthcare provider will inject IMLYGIC directly into your tumor(s) with a needle and syringe.

You will get a second treatment 3 weeks after the first treatment. After that, you will get treatments every 2 weeks for as long as you have tumor(s). You can get treated for 6 months or longer.

Your healthcare provider will decide which tumor(s) to inject and may not inject every one.

It is important to care for the treatment sites properly so that IMLYGIC does not spread to other people. Your healthcare provider will show you how to do this.

What should I avoid while getting IMLYGIC?

IMLYGIC virus can spread to other areas of your body or to your close contacts (household members, caregivers, sex partners, or persons sharing the same bed).

Do the following to avoid spreading IMLYGIC to other areas of your body or to your close contacts:

• Avoid direct contact between your treatment sites, dressings, or body fluids and close contacts (for example, use condoms when engaging in sexual activity, avoid kissing close contacts if either has an open mouth sore).
• Wear gloves while putting on or changing your dressings.
• Keep treatment sites covered with airtight and watertight dressings for at least 1 week after each treatment (or longer if the treatment site is weeping or oozing).
• If the dressing comes loose or falls off, replace it right away with a clean dressing.
• Place all used dressings and cleaning materials in a sealed plastic bag and throw them away in the garbage.
• Do not touch or scratch the treatment sites.

What are possible side effects of IMLYGIC?

The most common side effects of IMLYGIC include:

• Tiredness
• Chills
• Fever
• Nausea
• Flu-like symptoms
• Pain at treatment site

Tell your doctor right away if you get any of these signs and symptoms of herpes infection:

• Pain, burning, or tingling in a blister around the mouth or genitals or on the fingers or ears
• Eye pain, light sensitivity, discharge from the eyes, or blurry vision
• Weakness in arms or legs
• Extreme drowsiness (feeling sleepy)
• Mental confusion

If you think you have a herpes infection, inform your healthcare provider. You or your healthcare provider should call Amgen at 1-855-IMLYGIC (1-855-465-9442) for follow-up testing if needed.

These are not all the possible side effects of IMLYGIC. Your healthcare provider can give you more detailed information. Tell your healthcare provider if you have any side effects that bother you or that do not go away. You may report side effects to FDA at 1-800-FDA-1088.

What are the ingredients in IMLYGIC?

Active ingredient: talimogene laherparepvec

Inactive ingredients: di-sodium hydrogen phosphate dihydrate, sodium dihydrogen phosphate dihydrate, sodium chloride, myo-inositol, sorbitol, and water for injection

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

The most commonly reported adverse drug reactions (≥ 25%) in IMLYGIC-treated patients were fatigue, chills, pyrexia, nausea, influenza-like illness, and injection site pain.

The following adverse reactions are discussed in greater detail in another section of the label:

• Herpetic Infection [see WARNINGS AND PRECAUTIONS]
• Injection Site Complications [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.

The safety of IMLYGIC was evaluated in 419 patients who received at least 1 dose of either IMLYGIC (n = 292) or subcutaneously administered granulocyte-macrophage colony-stimulating factor (GM-CSF) (n = 127) in an open-label, randomized clinical study of patients with stage IIIB, IIIC, and IV melanoma that was not considered to be surgically resectable [see Clinical Studies]. The median duration of exposure to IMLYGIC was 23 weeks (5.3 months). Twenty-six patients were exposed to IMLYGIC for at least 1 year.

Most adverse reactions reported were mild or moderate in severity and generally resolved within 72 hours. The most common grade 3 or higher adverse reaction was cellulitis [see WARNINGS AND PRECAUTIONS].

Pyrexia, chills, and influenza-like illness can occur any time during IMLYGIC treatment but were more frequent during the first 3 months of treatment.

Table 4 below lists adverse reactions with a 5% or greater incidence in the IMLYGIC arm compared to the GM-CSF arm in the clinical study [see Clinical Studies].

Table 4. Advers e Reactions Reported with At Leas t a 5% Greater Incidence in Patients Treated with IMLYGIC Compared to GM-CSF

Other adverse reactions associated with IMLYGIC in the open-label, randomized study include rash, dermatitis, glomerulonephritis, vitiligo, worsening psoriasis, cellulitis, pneumonitis, vasculitis, herpetic keratitis, obstructive airway disorder, plasmacytoma at the injection site, deep vein thrombosis, and oral herpes.

Read the entire FDA prescribing information for Imlygic (Talimogene Laherparepvec Suspension for Intralesional Injection)