PAPZIMEOS

PAPZIMEOS is for subcutaneous injection only.

The recommended dosage of PAPZIMEOS is 5×10¹¹ particle units (PU) per injection administered as subcutaneous injection four times over a 12-week interval. The recommended dosing schedule for PAPZIMEOS is shown in Table 1.

Prior to the initial administration of PAPZIMEOS, perform a surgical debulking of visible papilloma to establish minimal residual disease. To maintain minimal residual disease during treatment with PAPZIMEOS, remove visible papilloma, if present, prior to the third and fourth administration of PAPZIMEOS.

PAPZIMEOS is a non-replicating adenoviral vector-based immunotherapy. Follow universal biosafety precautions for handling.

PAPZIMEOS is provided as a single-dose vial of sterile frozen suspension.

PAPZIMEOS MUST BE RAPIDLY thawed before use and prepared for immediate administration.

Once thawed, DO NOT place the PAPZIMEOS vial in a refrigerator, freezer, or on dry ice. Protect PAPZIMEOS from light. DO NOT shake the vial.

Administer PAPZIMEOS via subcutaneous injection with the following procedures:

1. Select the lateral regions of the upper arm and thigh for injection. Avoid areas of edema, potential infection, wounds, scars, or the site of a recent subcutaneous injection.
2. Clean the injection site thoroughly with an alcohol swab and allow at least 30 seconds to dry.
3. Inject PAPZIMEOS by inserting the needle at an angle to ensure delivery in the subcutaneous space.
4. Clean the area with an alcohol swab again, DO NOT massage the site of injection.
5. Place potentially contaminated materials from the injection site, including dressings, that may have the patient's bodily fluids/waste, in a sealable bag and dispose into regular trash. These precautions should be followed for 1-2 weeks after injection. Practice proper hand hygiene, such as hand washing, when coming into direct contact with patient body waste.
6. Avoid direct contact with the injection site (e.g., touching or scratching) and dressings for approximately 24 hours following treatment.

Injection-site reactions have occurred with PAPZIMEOS injection. Monitor patients for local site reactions for at least 30 minutes after the initial treatment and manage accordingly.

Thrombotic events may occur following administration of adenoviral vector-based therapies including PAPZIMEOS due to the potential to induce prothrombotic antibody development. Monitor patients for signs and symptoms of thrombotic events and treat events according to clinical practice.

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 data described in this section reflects exposure to PAPZIMEOS in one clinical study (Study PRGN-2012-201). A total of 38 adults with recurrent respiratory papillomatosis received a PAPZIMEOS dose of either 1×10¹¹ PU (n=3), or 5×10¹¹ PU (n=35) per injection on Days 1, 15, 43, and 85 [see Clinical Studies (14)]. The most common adverse reactions (incidence ≥5%) are summarized in Table 2.

Other clinically significant adverse reactions occurring in <5% of patients included vision blurred (3%), injection site bruising (3%), dizziness (3%), dyspnea (3%), and pruritus (3%).

The safety and effectiveness of PAPZIMEOS have not been established in pediatric patients.

There were 9 patients (24%) 65 years of age and older and 1 patient (3%) 75 years of age and older in Study PRGN-2012-201. Clinical studies of PAPZIMEOS did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger patients.

PAPZIMEOS is a non-replicating adenoviral vector-based immunotherapy designed to express a fusion antigen of selected regions of human papillomavirus (HPV) proteins expressed in HPV 6- and HPV 11-infected cells. PAPZIMEOS is designed to generate an immune response directed against HPV 6 and HPV 11 proteins in patients with recurrent respiratory papillomatosis.

The pharmacodynamic effect of PAPZIMEOS was evaluated in Study PRGN-2012-201 [see Clinical Studies (14)]. In 28 patients evaluated at completion of treatment, the induction of HPV 6- and HPV 11-specific T cell responses in RRP patients, was higher in RRP patients demonstrating a clinical response to treatment, i.e. reduction in or elimination of the requirement for surgical debulking during the 12 months following completion of treatment, with mean fold-change from baseline of 164.9 versus 5.1 (p<0.018). This difference persisted at 12 weeks post-treatment, with mean fold-change of 61.5 in responders versus 11.5 in non-responders.

No biodistribution and vector shedding studies have been conducted with PAPZIMEOS.

No animal studies have been performed to evaluate the effects of PAPZIMEOS on carcinogenesis, mutagenesis, or impairment of fertility.

Each carton of PAPZIMEOS (NDC 84768-511-01) contains one single-dose vial (NDC 84768-511-99) of PAPZIMEOS sterile frozen suspension.

PAPZIMEOS is supplied in a single-dose vial made from cyclic olefin polymer (COP) with a rubber stopper and aluminum flip-cap seal. Each vial is sealed inside a pouch (NDC 84768-511-00). The pouch is placed in the container along with a Package Insert. Each vial is formulated to contain an extractable dose of 5×10¹¹ PU in a 1 mL suspension.

PAPZIMEOS is shipped and stored frozen at ≤ -60°C [≤ -76°F] and should be stored in an appropriate freezer at ≤ -60°C [≤ -76°F] until ready to thaw and administer.

DO NOT place the vial in a refrigerator, freezer, or on dry ice at any time once removed from the pouch. Protect the vials from light. DO NOT shake the vial.

PAPZIMEOS should not be held at room temperature for more than 60 minutes after thawing.

PAPZIMEOS is a non-replicating adenoviral vector-based immunotherapy. Follow universal biohazard precautions for handling [see Dosage and Administration (2.2)(2.3)] and for the disposal of all vials and syringes.