b'USMAd_v1.pdf 3 11/30/21 7:55 AMUnsolicited Adverse Events 8USE IN SPECIFIC POPULATIONSUnsolicited adverse events within 28 days following any injection, including placebo, were8.1Pregnancyreported by 35.4% of HEPLISAV-B recipients and 36.2% of Engerix-B recipients. Pregnancy Exposure RegistrySerious Adverse Events There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to HEPLISAV-B during pregnancy. Women who receive HEPLISAV-B during vaccine. The percentage of subjects reporting serious adverse events was 3.9% in thepregnancy are encouraged to contact 1-844-443-7734.HEPLISAV-B group and 4.8% in the Engerix-B group. Acute myocardial infarction occurredRisk Summaryin 0.1% (n=2) of HEPLISAV-B recipients and 0.2% (n=1) of Engerix-B recipients. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In clinically Autoimmune Adverse Events recognized pregnancies in the US general population, the estimated background risk of Subjects were monitored for the occurrence of new-onset potentially immune-mediatedmajor birth defects is 2% to 4% and of miscarriage is 15% to 20%.There are no clinical studies of HEPLISAV-B in pregnant women. Available human data on to whether they were autoimmune by an external group of experts blinded to treatment assignment. As determined by the adjudicators, new-onset autoimmune adverse eventsrisks in pregnancy.were reported in 0.2% (n=3) of HEPLISAV-B recipients: two subjects with hypothyroidismIn a developmental toxicity study, 0.3 mL of a vaccine formulation containing 2.5 mcg and one subject with vitiligo. None of these events was considered related to vaccinationHBsAg and 3000 mcg cytosine phosphoguanine (CpG) 1018 adjuvant was administered by the expert group. No new-onset autoimmune adverse events were reported in theto female rats prior to mating and during gestation. These animal studies revealed no Engerix-B group. Although not referred to the external group of experts, one HEPLISAV-Bevidence of harm to the fetus due to this vaccine formulation [see Data].recipient was determined to have Tolosa-Hunt syndrome which is presumed to have anDataimmune-mediated etiology. This event was not considered related to vaccination. Animal dataDeaths Developmental toxicity studies were conducted in female rats. Animals were administered One subject (0.05%) died of a pulmonary embolism in the HEPLISAV-B group and 1 subject0.3 mL of a vaccine formulation containing 2.5 mcg HBsAg and 3000 mcg CpG 1018 (0.2%) died of heart failure in the Engerix-B group. Neither death was considered relatedadjuvant twice prior to mating, and on gestation days 6 and 18 (a single human dose to vaccination. of HEPLISAV-B contains 20 mcg HBsAg and 3000 mcg CpG 1018 adjuvant). No adverse Study 3 in Subjects 18 through 70 Years of Age effects on pre-natal and post-natal development up to the time of weaning were observed. Study 3 was a randomized, observer-blind, active-controlled, multicenter study in theThere were no vaccine-related fetal malformations or variations observed.United States in which 5587 subjects received at least 1 dose of HEPLISAV-B and 8.2Lactation2781 subjects received at least 1 dose of Engerix-B. Enrolled subjects had no history ofRisk Summaryhepatitis B vaccination or infection. HEPLISAV-B was given as a 2-dose regimen at 0 and It is not known whether HEPLISAV-B is excreted in human milk. Data are not available to 1 month followed by saline placebo at 6 months. Engerix-B was given at 0, 1, and assess the effects of HEPLISAV-B on the breastfed infant or on milk production/excretion.6 months. In the total study population, the mean age was 50 years; 51% were men; 71% were white, 26% black, 1% Asian, and 9% Hispanic; 48% were obese, 36% hadwith the mothers clinical need for HEPLISAV-B and any potential adverse effects on the hypertension, 32% had dyslipidemia, and 14% had type 2 diabetes mellitus. Thesebreastfed child from HEPLISAV-B or from the underlying maternal condition. For preventive demographic and baseline characteristics were similar in both vaccine groups. vaccines, the underlying condition is susceptibility to disease prevented by the vaccine.Unsolicited Medically-Attended Adverse Events 8.4Pediatric UseSubjects were monitored for unsolicited medically-attended adverse events, those forSafety and effectiveness of HEPLISAV-B have not been established in individuals less than medically-attended adverse events were reported in 46.0% of HEPLISAV-B recipients18 years of age.and 46.2% of Engerix-B recipients. Herpes zoster was reported in 0.7% of HEPLISAV-B8.5Geriatric Userecipients and 0.3% of Engerix-B recipients. Unsolicited medically-attended adverseClinical trials included 909 adults 65 through 70 years of age who received HEPLISAV-B.events within 28 days following any injection, including placebo, were reported by 20.1%Among subjects who received HEPLISAV-B, a seroprotective level of antibody to HBsAg of both HEPLISAV-B and Engerix-B recipients. was achieved in 90% of those 65 through 70 years of age compared to 96% of those aged Serious Adverse Events18 through 64 years of age.Safety and effectiveness of HEPLISAV-B in adults older than 70 years of age were of vaccine. The percentage of subjects who reported serious adverse events was 6.2% in the HEPLISAV-B group and 5.3% in the Engerix-B group. Acute myocardial infarction8.6Adults on Hemodialysis(AMI) was reported in 0.25% (n=14) of HEPLISAV B recipients and 0.04% (n=1) ofSafety and effectiveness of HEPLISAV-B have not been established in adultsEngerix-B recipients. An analysis of serious adverse events likely representing myocardialon hemodialysis. infarction (MI) was conducted using the standard Medical Dictionary for Regulatory 17.PATIENT COUNSELING INFORMATIONsubjects (0.3%) and 3 Engerix-B subjects (0.1%) with events included in the SMQ for MI (these events include the 15 reports of AMI). Additional evidence, including informationvaccination, as well as the importance of completing the immunization series.on temporal relationship and baseline risk factors, does not support a causal relationship cause hepatitis B infection.HEPLISAV-B recipients, three occurred within 14 days, nine occurred within 53-180 days, Advise vaccine recipient to report any adverse events to their healthcare providerand seven occurred more than 180 days following any dose of HEPLISAV-B. Among theor to the Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 and www.vaers.hhs.gov.203 days following any dose. All 19 HEPLISAV-B recipients and 3 Engerix-B recipients Provide the Vaccine Information Statements, which are available free of chargereported one or more baseline risk factors for cardiovascular disease.at the Centers for Disease Control and Prevention (CDC) website Autoimmune Adverse Events (www.cdc.gov/vaccines).Subjects were monitored for the occurrence of new-onset potentially immune-mediated to whether they were autoimmune by an external group of experts who were blinded to treatment assignment. As determined by the adjudicators, new-onset autoimmune adverseManufactured by: events were reported in 0.1% (n=4) of HEPLISAV-B recipients [one each of: alopeciaDynavax Technologies Corporation areata, polymyalgia rheumatica, ulcerative colitis, and autoimmune thyroiditis (withEmeryville, CA 94608 USAconcurrent diagnosis of papillary thyroid carcinoma)]. None of these events was considered 2020, Dynavax Technologies Corporation. All rights reserved.to be related to vaccination by the external experts. No new-onset autoimmune adverseUS-20-00-00172events were reported in the Engerix-B group.DeathsDuring the study death was reported in 25 subjects (0.4%) in the HEPLISAV-B group and7 subjects (0.3%) in the Engerix-B group. No death was considered related to vaccination.7DRUG INTERACTIONS7.1Use with Immune GlobulinThere are no data to assess the concomitant use of HEPLISAV-B with immune globulin. When concomitant administration of HEPLISAV-B and immune globulin is required, they should be given with different syringes at different injection sites.7.2Interference with Laboratory TestsHepatitis B surface antigen (HBsAg) derived from hepatitis B vaccines has been transiently detected in blood samples following vaccination. Serum HBsAg detection may not have diagnostic value within 28 days after receipt of HEPLISAV-B.'