DEPEMOKIMAB: 14 Adverse Event Reports & Safety Profile

Depemokimab‑ulaa is an interleukin‑5 (IL‑5) antagonist monoclonal antibody (humanized Immunoglobulin G1 [IgG1] kappa). Depemokimab‑ulaa is produced by recombinant DNA technology in Chinese hamster ovary cells. The estimated molecular weight of depemokimab‑ulaa is 149 kDa. EXDENSUR (depemokimab‑ulaa) injection is a sterile, preservative‑free, colorless, yellow to brown, clear to opalescent solution for subcutaneous (SC) use. EXDENSUR injection is supplied in a single‑dose, 1‑mL, prefilled pen with a fixed 29‑gauge, half‑inch needle or in a single‑dose, 1‑mL, prefilled syringe with a fixed 29‑gauge, half‑inch needle with a needle guard.

Each

1 mL delivers 100 mg depemokimab‑ulaa, (8.43 mg) arginine HCl, (0.017 mg) edetate disodium, (1.41 mg) histidine, (2.29 mg) L‑histidine HCl monohydrate, (0.20 mg) polysorbate 80, (61.6 mg) trehalose, and Water for Injection with a pH of 6.0.

AND USAGE EXDENSUR is indicated for the add‑on maintenance treatment of severe asthma characterized by an eosinophilic phenotype in adult and pediatric patients aged 12 years and older. Limitations of Use EXDENSUR is not indicated for the relief of acute bronchospasm or status asthmaticus [see Warnings and Precautions ( 5.2 )] . EXDENSUR is an interleukin‑5 (IL-5) antagonist, a monoclonal antibody (humanized immunoglobulin G [IgG]1 kappa) indicated for add-on maintenance treatment of severe asthma characterized by an eosinophilic phenotype in adult and pediatric patients aged 12 years and older. ( 1 ) Limitations of Use: Not for relief of acute bronchospasm or status asthmaticus. ( 1 )

AND ADMINISTRATION The recommended dosage is 100 mg administered once every 6 months by subcutaneous (SC) injection into the upper arm, thigh, or abdomen. ( 2.1 )

• EXDENSUR should be administered by a healthcare provider. ( 2.2 )
• See full prescribing information for preparation and administration instructions. ( 2.2 )

2.1 Recommended Dosage The recommended dosage is 100 mg once every 6 months administered by subcutaneous (SC) injection into the upper arm, thigh, or abdomen avoiding 2 inches (5 cm) around the navel <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2 )]</span> .

Missed

Dose(s) If a dose is missed, administer the missed dose as soon as possible and resume the once every 6‑month injection schedule from the date of when the missed dose was given.

2.2 Preparation and Administration Instructions for EXDENSUR

• EXDENSUR is for subcutaneous (SC) use only.
• EXDENSUR should be administered by a healthcare provider. Do not use EXDENSUR prefilled pen or syringe if the security seal on the carton has been broken. Do not use EXDENSUR prefilled pen or syringe if it has been dropped or damaged.

Preparation Instructions

1. Remove the prefilled pen or prefilled syringe from the refrigerator. Holding the middle of the prefilled pen or prefilled syringe, take it out from the tray and allow it to sit at room temperature for 30 minutes prior to injection. Do not warm EXDENSUR injection in any other way. Do not remove the needle cap until you are ready to inject. Do not use the pen or syringe if it has been left out of the carton for more than 8 hours. 2. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. EXDENSUR should be colorless to yellow to brown, clear to opalescent in color. Do not use EXDENSUR if the product exhibits discoloration, cloudiness, or particulate matter. It is normal to see an air bubble. Do not expel the air bubble prior to administration. Do not shake the device. 3. Choose the Injection Site Administer the injection into upper arm, thigh, or abdomen, avoiding the 2 inches (5 cm) around the navel. Do not give injections into areas where the skin is tender, bruised, red, or hard.

Administration

Instructions for Single ‑ Dose Prefilled Pen Figure 1.

Exdensur

Prefilled Pen Components 1.

Pull

Off the Clear Cap Remove the clear cap by pulling it straight off, away from the yellow needle guard. Do not press the yellow needle guard. Do not put the cap back on the pen. This could accidentally start the injection. Inject within 5 minutes after removing the clear cap. 2. Position the Pen at the Injection Site and Press Firmly to Start the Injection Place the yellow needle guard flat against the skin (at a 90 degree angle to the skin). Make sure you can see the inspection window. The yellow needle guard will slide up into the pen. You may hear a “click” that tells you the injection has started. Do not use the pen if the yellow needle guard does not slide up into the pen. 3. Continue to Hold Down Keep the pen held down against the skin. Do not lift or move the pen during the injection. The yellow indicator will move down through the inspection window during the injection. The injection is done when you hear the second click. Injection may take up to 20 seconds. If you do not hear the second click, check that:

• The inspection window is filled with the yellow indicator.
• The black stopper has stopped moving. 4.

Lift Pen After Injection Completes

5.

Throw Away

Dispose of used pen and clear cap according to local health and safety laws.

Administration

Instructions for Single ‑ Dose Prefilled Syringe Figure 2.

Exdensur

Prefilled Syringe Components 1.

Pull

Off the Gray Needle Cap Remove the gray needle cap from the syringe by pulling it straight off, away from the needle. Do not handle the syringe by the white plunger while removing the gray needle cap. Do not put the gray needle cap back onto the syringe. Inject within 5 minutes after removing the gray needle cap. 2. Position the Syringe at the Injection Site Use your free hand to gently pinch the skin around the cleaned injection site. Do not handle the syringe by the white plunger while inserting the needle into the pinched skin. Hold the middle of the syringe and insert the entire needle into the pinched skin at a 45 degree angle, as shown. 3. Start the Injection and Fully Press the White Plunger Slowly push down on the white plunger with your thumb to inject the full dose. Make sure the white plunger is pushed all the way down until the stopper reaches the bottom of the syringe and all of the medication is injected. 4.

Slowly Lift Thumb After Injection

Completes Slowly lift your thumb up. This will allow the white plunger to come up and the needle to automatically pull up (retract) into the needle guard. After removing the syringe from the injection site, release the pinched skin. 5.

Throw Away

Dispose of used syringe according to local health and safety laws.

Figure

1 1.

Pull

Off the Clear Cap 2. Position the Pen at the Injection Site and Press Firmly to Start the Injection 3. Continue to Hold Down Figure 2 1.

Pull

Off the Gray Needle Cap 2. Position the Syringe at the Injection Site 3. Start the Injection and Fully Press the White Plunger 4.

Slowly Lift Thumb After Injection

Completes

None. None. ( 4 )

REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] . The most common adverse reactions (incidence ≥4%) are upper respiratory tract infection, allergic rhinitis, influenza, arthralgia, and pharyngitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of EXDENSUR was based on a pooled safety population from 2 replicate, randomized, double‑blind, parallel‑group, placebo‑controlled, multicenter clinical trials (SWIFT‑1 and SWIFT‑2) of 52 weeks duration.

The

2 trials included 762 adult and pediatric patients 12 years of age and older with asthma, who received either EXDENSUR 100 mg or placebo administered subcutaneously once every 6 months in addition to their existing background medications for asthma [see Clinical Studies ( 14 )] . A total of 475 patients received 2 doses of EXDENSUR 100 mg in these trials. Adverse reactions with EXDENSUR with incidence of ≥4% are shown in Table 1 .

Table

1.

Adverse

Reactions with EXDENSUR with an Incidence ≥4% and More Common than Placebo in Patients with Asthma Adverse Reaction EXDENSUR (N = 501) n (%) Placebo (N = 261) n (%) Upper respiratory tract infection 46 (9) 20 (8) Allergic rhinitis 29 (6) 7 (3)

Influenza

24 (5) 11 (4)

Arthralgia

19 (4) 8 (3)

Pharyngitis

18 (4) 3 (1)

Specific Adverse Reactions Injection Site

Reactions: In the pooled safety population (SWIFT‑1 and SWIFT‑2), in which EXDENSUR was administered by a healthcare provider, injection site reactions (e.g., erythema, swelling, and itching) occurred in 7 (1%) and 2 (<1%) patients receiving EXDENSUR and placebo, respectively.

AND PRECAUTIONS

• Hypersensitivity reactions, including anaphylaxis, can occur after administration of EXDENSUR. If a hypersensitivity reaction occurs, discontinue EXDENSUR and initiate appropriate therapy. ( 5.1 )
• Do not abruptly discontinue systemic or inhaled corticosteroids upon initiation of therapy with EXDENSUR. Reduce corticosteroid dose gradually, if appropriate. ( 5.3 )
• Treat pre-existing helminth infections before initiating therapy with EXDENSUR. If patients become infected while receiving treatment with EXDENSUR and do not respond to anti‑helminth treatment, discontinue EXDENSUR until the parasitic infection resolves. ( 5.4 )

5.1 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, can occur following administration of EXDENSUR. If a hypersensitivity reaction occurs, discontinue EXDENSUR and initiate appropriate therapy.

5.2 Acute Asthma Symptoms or Deteriorating Disease EXDENSUR should not be used to treat acute asthma symptoms or acute exacerbations. Do not use EXDENSUR to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with EXDENSUR.

5.3 Risk Associated with Abrupt Reduction of Corticosteroid Dosage Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy. Do not abruptly discontinue systemic or inhaled corticosteroids upon initiation of EXDENSUR therapy. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the supervision of a healthcare provider.

5.4 Parasitic (Helminth)

Infection

Eosinophils may be involved in the immunological response to some helminth infections. Patients with pre‑existing helminth infections were excluded from participation in the clinical trials. It is unknown if EXDENSUR will influence a patient’s response against parasitic infections. Patients with pre‑existing helminth infections should be treated for their infection prior to initiation of EXDENSUR therapy. If patients become infected while receiving treatment with EXDENSUR and do not respond to anti‑helminth treatment, discontinue treatment with EXDENSUR until the infection resolves.