Dawnzera Drug Information

DAWNZERA™ is indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. DAWNZERA is a prekallikrein directed antisense oligonucleotide indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older.

Recommended Dosage

The recommended dosage of DAWNZERA is 80 mg administered subcutaneously every 4 weeks. A dosage of 80 mg administered subcutaneously every 8 weeks may be considered. Missed Dose(s) If a dose of DAWNZERA is missed, administer DAWNZERA as soon as possible.

Resume treatment at the recommended dosing frequency from the date of the most recently administered dose.

Administration Instructions For subcutaneous use.

DAWNZERA is intended for self-administration or administration by a caregiver. Prior to treatment initiation, train patients and/or caregivers on proper preparation and subcutaneous administration technique of DAWNZERA autoinjector . Remove the single‑dose autoinjector from the refrigerator 30 minutes prior to the injection and allow to warm to room temperature. Do not use other warming methods.

Inspect DAWNZERA visually for particulate matter and discoloration prior to administration. The solution should appear clear and colorless to yellow. Do not use if cloudiness, particulate matter, or discoloration is observed prior to administration.

Administer DAWNZERA subcutaneously into the abdomen or upper thigh region. The back of the upper arm can also be used as an injection site if a caregiver or healthcare provider administers the injection.

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 DAWNZERA reflects the exposure in a total of 171 adult and pediatric patients 12 years and older with hereditary angioedema (HAE) from a placebo-controlled trial (OASIS-HAE) , and 2 other clinical studies. The average duration of DAWNZERA treatment exposure across the 3 clinical studies was 14 months.

The safety data below is based on the 24-week multicenter, randomized, double-blind, placebo-controlled trial (OASIS-HAE), in which patients received at least one subcutaneous dose of DAWNZERA 80 mg once every 4 weeks (n=45), DAWNZERA 80 mg once every 8 weeks (n=23), or matching placebo (n=22). Demographics of the patients in OASIS-HAE are summarized in Clinical Studies . Table 1 provides the most common adverse reactions with DAWNZERA with incidence ≥5% and more common than placebo. Table 1: Adverse Reactions with DAWNZERA with Incidence ≥5% and More Common than Placebo in Patients with HAE (OASIS-HAE) N = number of patients; n = number of patients experiencing the event; q4wks = every 4 weeks; q8wks = every 8 weeks. * Injection site reactions include: erythema, discoloration, pain, pruritus, induration, bruising, haematoma, hypersensitivity, swelling, reaction, and urticaria. † All injection site reactions were mild, nonserious, and the majority of them resolved without receiving any treatment. Adverse Reaction DAWNZERA Placebo (N=22) 80 mg q4wks (N=45) 80 mg q8wks (N=23) n (%) n (%) n (%) Injection site reactions*† 11 1 1 Upper respiratory tract infection 4 2 1 Urinary tract infection 4 2 0 Abdominal discomfort 3 0 0 Specific Adverse Reactions Hypersensitivity Reactions, Including Anaphylaxis In clinical trials, hypersensitivity reactions, including anaphylaxis, have occurred.

Symptoms included generalized rash, dyspnea, chest pain, and peri-oral swelling. Laboratory Tests Decrease in Platelet Count : DAWNZERA can cause reductions in platelet count. In OASIS-HAE, the mean platelet count at baseline was 266,000/mm 3 for the DAWNZERA 80 mg every 4 weeks group, 265,000/mm 3 for the DAWNZERA 80 mg every 8 weeks group, and 245,000/mm 3 for the placebo group.

The mean percent change in platelet count at Week 25 was -9.6% for the DAWNZERA 80 mg every 4 weeks group, -7.9% for the DAWNZERA 80 mg every 8 weeks group, and -1.4% for the placebo group. In OASIS-HAE and 2 other clinical studies no DAWNZERA-treated patient had a platelet count of <50,000/mm 3, and there were no major bleeding events associated with a low platelet count. Increase in Liver Function Tests : Increases from baseline in liver enzymes (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase) were observed with DAWNZERA use.

The increased levels were generally below 3 times the upper limit of normal and stabilized. Discontinuations due to liver function test increases were infrequent.

Pregnancy Risk Summary There are no available data on DAWNZERA use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, subcutaneous administration of donidalorsen or a pharmacologically active mouse‑specific surrogate in a combined fertility and embryo‑fetal development study in mice and a pre‑ and postnatal development study in mice with F0 parental doses up to 5 times the maximum recommended human dose (MRHD, 80 mg) on a body surface area (BSA, mg/m 2 ) basis did not result in any adverse effects on embryofetal development, or behavioral, fertility, and reproductive development in the F1 offspring. Donidalorsen does not cross the placental barrier (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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. Data Animal Data In reproductive toxicity studies with donidalorsen, the unconjugated form was not detected (below the limit of quantitation) in fetal tissues.

Donidalorsen does not cross the placental barrier. In a combined fertility and embryofetal development study, subcutaneous administration of donidalorsen (up to 10 mg/kg/week ) or a mouse‑specific surrogate (4 mg/kg/week) to male and female F0 mice weekly, prior to and during mating, and continuing every other day in females throughout the periods of implantation and organogenesis (Gestation Days 0 to 16), resulted in no adverse effects on embryofetal development. There was no evidence of maternal toxicity with doses up to 10 mg/kg/week.

In a pre- and postnatal development study, subcutaneous administration of donidalorsen (up to 20 mg/kg/week ) or a mouse-specific surrogate (5 mg/kg/week) to F0 female mice every other day throughout pregnancy (from Gestation Day 6 to 18) and weekly throughout lactation (from Lactation Day 1 to 20) produced no adverse effects on behavioral, fertility, and reproductive development in the F1 offspring. There was no evidence of maternal toxicity with doses up to 20 mg/kg/week.

Pediatric Use The safety and effectiveness of DAWNZERA for prophylaxis to prevent attacks of HAE have been established in pediatric patients aged 12 years and older. Use of DAWNZERA for this indication is supported by evidence from an adequate and well‑controlled trial (OASIS-HAE) that included 7 pediatric patients (aged 12 to 17 years) who received DAWNZERA 80 mg subcutaneously every 4 weeks (n=4) or every 8 weeks (n=3). The safety and effectiveness of DAWNZERA in pediatric patients aged 12 years and older is extrapolated from adults from OASIS-HAE with support from pharmacokinetic analysis and pharmacodynamic response . No new safety signals were identified in pediatric patients aged 12 years and older who received DAWNZERA . The safety and effectiveness of DAWNZERA have not been established in pediatric patients younger than 12 years of age.

is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA . History of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA.