Zopapogene Imadenovec

PAPZIMEOS is indicated for the treatment of adults with recurrent respiratory papillomatosis. PAPZIMEOS™ is a non-replicating adenoviral vector-based immunotherapy indicated for the treatment of adults with recurrent respiratory papillomatosis. ( 1 )

PAPZIMEOS is supplied as a slightly opalescent to opalescent, colorless suspension for subcutaneous injection with a concentration of 5×10 11 PU/mL. Each single-dose vial delivers a minimum extractable volume of 1 mL [see How Supplied/Storage and Handling ( 16 ) ]. PAPZIMEOS is supplied in a single-dose vial that contains 5×10 11 PU in an extractable volume of 1 mL of suspension. ( 3 )

None. None. ( 4 )

Injection-site reactions: Injection-site reactions, have been observed. Monitor patients for local site reactions for at least 30 minutes after the initial treatment. ( 5.1 ) Thrombotic events: Thrombotic events may occur following administration of adenoviral vector-based therapies. Monitor patients for signs and symptoms of thrombotic events and treat events according to clinical practice. ( 5.2 )

5.1 Injection-Site Reactions 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.

5.2 Thrombotic Events 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.

The most common adverse reactions (incidence ≥5%) were injection site reactions, fatigue, chills, pyrexia, myalgia, nausea, headache, tachycardia, diarrhea, vomiting, and hyperhidrosis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Precigen Inc. at 855-743-6777 and medinfo@precigen.com 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 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 1×10 11 PU (n=3), or 5×10 11 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 . Table 2: Adverse Reactions occurring in ≥5% of Patients in Study PRGN-2012-201 (N=38) *Graded per NCI CTCAE v5.0. There were no Grade >2 adverse reactions. Preferred Term Grade 1-2* n (%) Injection site reaction 37 (97) Fatigue 28 (74) Chills 25 (66) Pyrexia 24 (63) Myalgia 11 (29) Nausea 10 (26) Headache 4 (11) Tachycardia 3 (8) Diarrhea 2 (5) Vomiting 2 (5) Hyperhidrosis 2 (5) 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%).

8.1 Pregnancy Risk Summary There are no available data with PAPZIMEOS in pregnant women. Animal reproductive and developmental toxicity studies have not been conducted with PAPZIMEOS. In the PRGN-2012-201 study, one patient reported pregnancy at 6 months following completion of treatment with PAPZIMEOS. The patient delivered at 40 weeks without any reported birth complications or neonatal concerns. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

8.2 Lactation Risk Summary There is no information available on the presence of PAPZIMEOS in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PAPZIMEOS and any potential adverse effects on the breastfed child from PAPZIMEOS or from the underlying maternal condition.

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

8.5 Geriatric Use 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.