Atacicept

TRUTAKNA is indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression. This indication is approved under accelerated approval based on reduction of proteinuria. It has not been established whether TRUTAKNA slows kidney function decline over the long-term in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. TRUTAKNA is a B-lymphocyte stimulator (BLyS)-specific inhibitor and A Proliferation Inducing Ligand (APRIL) blocker indicated to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk for disease progression. ( 1 ). This indication is approved under accelerated approval based on a reduction of proteinuria. It has not been established whether TRUTAKNA slows kidney function decline over the long-term in patients with IgAN. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial.

150 mg once weekly by subcutaneous injection. ( 2.2 )

2.1 Recommended Dosage The recommended dosage of TRUTAKNA is 150 mg injected subcutaneously (SC) once weekly. Missed Doses If a dose is missed, administer the missed dose as soon as possible and then resume once weekly dosing thereafter, one week from administration of the missed dose.

2.2 Preparation and Administration Instructions TRUTAKNA autoinjector is intended for SC administration by patients/caregivers at home. The TRUTAKNA “Instructions for Use” contains more detailed instructions on the preparation and administration of TRUTAKNA [see Instructions for Use ] . Remove TRUTAKNA autoinjector from the refrigerator and allow it to sit for 15 to 30 minutes at room temperature between 15°C to 25°C (60°F to 77°F) prior to injecting. Do not use an external heat source to heat TRUTAKNA, because heat may damage the product. If needed, TRUTAKNA autoinjector may be stored at room temperature up to 25°C (77°F), for a single period of 3 days (72 hours). Once TRUTAKNA has been stored at room temperature, it should not be placed back into the refrigerator. Discard the autoinjector if not used within this 72‑hour period. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. TRUTAKNA should appear as a clear to slightly opalescent, brownish-yellow solution. Do not use if the liquid contains particles or is cloudy. Administer each injection at a different location than the previous injection. Sites for injections include the abdomen and thigh.

TRUTAKNA is a clear to slightly opalescent, brownish-yellow solution, free of visible particles, available as follows: Injection: 150 mg/mL in a single-dose pre-filled autoinjector Injection: 150 mg/mL in a single-dose pre-filled autoinjector. ( 3 )

TRUTAKNA is contraindicated in patients with serious hypersensitivity to atacicept-vymj or any excipients of TRUTAKNA. Serious hypersensitivity to any of the ingredients in TRUTAKNA. ( 4 )

5 WARNINGS AND PRECAUTIONS Immunosuppression and Increased Risk of Infections: Delay initiation of TRUTAKNA during an active infection. During treatment, monitor for signs and symptoms of infections and consider interrupting TRUTAKNA if the infection becomes serious. ( 5.1 ) Immunosuppression and Immunization Risks : Live vaccines not recommended within 30 days prior to initiation of TRUTAKNA or during treatment. ( 5.2 )

5.1 Immunosuppression and Increased Risk of Infections TRUTAKNA suppresses the immune system by reducing antibody production, which may increase the risk of infections. Patients with a chronic infection or recurring infections may have an increased risk of serious infection. In clinical trials, infections were reported in 32% of patients in the TRUTAKNA group compared with 28% of participants in the placebo group [ see Adverse Reactions ( 6.1 ) ]. Before initiating TRUTAKNA, assess patients for active infections. Delay TRUTAKNA administration in patients with active infection until the infection resolves or is adequately treated. During treatment, monitor patients for signs and symptoms of infection. If a serious infection develops, consider interrupting TRUTAKNA until the infection is controlled. The concomitant use of TRUTAKNA and other immune-modulating therapies has not been evaluated. Concomitant use of TRUTAKNA with drugs that affect the immune system, including systemic corticosteroids, may increase the risk of infection.

5.2 Immunosuppression and Immunization Risks TRUTAKNA may interfere with the immune responses to vaccines and increase the risk of infection from live vaccines. Prior to initiating treatment with TRUTAKNA, complete all age appropriate immunizations according to current immunization guidelines. Live vaccines are not recommended within 30 days prior to initiation of TRUTAKNA or during treatment with TRUTAKNA as safety of coadministration has not been established.

The following clinically significant adverse reactions are described elsewhere in the labeling: Immunosuppression and Increased Risk of Infections [see Warnings and Precautions ( 5.1 )] Immunosuppression and Immunization Risks [see Warnings and Precautions ( 5.2 )] The most common adverse reactions with TRUTAKNA (incidence ≥5% and greater than placebo) were upper respiratory tract infection, injection site reaction and injection site erythema. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vera Therapeutics at 1-833-633-8372 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 of TRUTAKNA was evaluated in a randomized, double-blind, placebo-controlled clinical study in 428 adults with IgAN (Origin 3). The median duration of exposure was 34 weeks in the 214 patients treated with TRUTAKNA and 31 weeks in the 214 patients administered placebo [see Clinical Studies ( 14 )] . The most common adverse reactions (reported in ≥5% of patients treated with TRUTAKNA and at a higher incidence than placebo) in patients treated with TRUTAKNA and placebo, respectively, were infections (32% vs. 28%) and local administration reactions (30% vs. 5%). The most common infection was upper respiratory tract infection (12% vs. 9%), and the most common local administration reactions were injection site reaction (19% vs. 2%) and injection site erythema (6% vs. 1%). Most adverse reactions observed in the TRUTAKNA group were mild or moderate in severity and resolved without treatment interruption or discontinuation.

8.1 Pregnancy Risk Summary Available data on TRUTAKNA use in pregnant women exposed during clinical trials are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Based on mechanism of action, TRUTAKNA may cause immunosuppression in the in utero-exposed infant [see Warnings and Precautions ( 5.1 and 5.2 ), Clinical Pharmacology ( 12.1 ) and Clinical Considerations ] . There are risks to the mother and infant with untreated IgAN nephropathy in pregnancy (see Clinical Considerations ) . In animal reproduction studies, no treatment-related malformations were observed in mice and rabbits at atacicept-vymj exposures approximately up to 12 times and 4 times, respectively, the clinical exposure at the recommended human dose (RHD) (see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Pregnant women exposed to TRUTAKNA, or their healthcare providers, should report TRUTAKNA exposure by calling 1-833-633-8372. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk IgAN in pregnancy is associated with adverse maternal outcomes, including increased rates of cesarean section, pregnancy-induced hypertension, pre-eclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including stillbirth and low birth weight. Fetal/Neonatal Adverse Reactions Based on mechanism of action, TRUTAKNA may cause immunosuppression in the in utero exposed infant. The potential clinical impact of TRUTAKNA exposure in infants exposed in utero should be considered. Data Animal Data In pregnant mice, SC administration of atacicept-vymj once every two days (0, 5, 20, and 80 mg/kg) throughout organogenesis from gestation day (GD) 6 to 15 did not result in any adverse effects on embryofetal development at up to 80 mg/kg, approximately 12 times the clinical exposure at the RHD based on area under the concentration curve (AUC). In pregnant rabbits, SC administration of atacicept-vymj once every two days (0, 5, 20, and 80 mg/kg) throughout organogenesis from GD 6 to 18 resulted in early and late resorptions, reduced number of live fetuses, and decreased mean fetal weight at ≥20 mg/kg, doses that resulted in maternal toxicity (reduced body weight gain). Exposures at these doses were ≥4 times the clinical exposure at the RHD, based on AUC. Embryofetal malformations (enlarged bregmatic fontanella, severe reduction of ossification of parietal or frontal bones, and unossified interparietal bones) were observed at 80 mg/kg (maternally toxic dose), approximately 11 times the clinical exposure at the RHD, based on AUC. No treatment-related malformations were observed at up to 20 mg/kg, approximately 4 times the clinical exposure at the RHD, based on AUC. In a pre- and post-natal development study in mice, SC administration of atacicept-vymj once every two days (0, 5, 20, or 80 mg/kg) throughout pregnancy and lactation (GD 6 to lactation day 21) did not result in adverse effects on maternal function or development of offspring at up to 80 mg/kg, approximately 12 times the clinical exposure at the RHD based on AUC.

8.2 Lactation Risk Summary There are no data regarding the presence of atacicept-vymj in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TRUTAKNA and any potential adverse effects on the breastfed child from TRUTAKNA or from the underlying maternal condition.

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

8.5 Geriatric Use Clinical studies of TRUTAKNA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger adult patients. No clinically meaningful differences in the pharmacokinetics of TRUTAKNA were observed in patients aged 65 and over compared to younger adult patients.

Risk Summary Available data on TRUTAKNA use in pregnant women exposed during clinical trials are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Based on mechanism of action, TRUTAKNA may cause immunosuppression in the in utero-exposed infant [see Warnings and Precautions ( 5.1 and 5.2 ), Clinical Pharmacology ( 12.1 ) and Clinical Considerations ] . There are risks to the mother and infant with untreated IgAN nephropathy in pregnancy (see Clinical Considerations ) . In animal reproduction studies, no treatment-related malformations were observed in mice and rabbits at atacicept-vymj exposures approximately up to 12 times and 4 times, respectively, the clinical exposure at the recommended human dose (RHD) (see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Pregnant women exposed to TRUTAKNA, or their healthcare providers, should report TRUTAKNA exposure by calling 1-833-633-8372. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk IgAN in pregnancy is associated with adverse maternal outcomes, including increased rates of cesarean section, pregnancy-induced hypertension, pre-eclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including stillbirth and low birth weight. Fetal/Neonatal Adverse Reactions Based on mechanism of action, TRUTAKNA may cause immunosuppression in the in utero exposed infant. The potential clinical impact of TRUTAKNA exposure in infants exposed in utero should be considered. Data Animal Data In pregnant mice, SC administration of atacicept-vymj once every two days (0, 5, 20, and 80 mg/kg) throughout organogenesis from gestation day (GD) 6 to 15 did not result in any adverse effects on embryofetal development at up to 80 mg/kg, approximately 12 times the clinical exposure at the RHD based on area under the concentration curve (AUC). In pregnant rabbits, SC administration of atacicept-vymj once every two days (0, 5, 20, and 80 mg/kg) throughout organogenesis from GD 6 to 18 resulted in early and late resorptions, reduced number of live fetuses, and decreased mean fetal weight at ≥20 mg/kg, doses that resulted in maternal toxicity (reduced body weight gain). Exposures at these doses were ≥4 times the clinical exposure at the RHD, based on AUC. Embryofetal malformations (enlarged bregmatic fontanella, severe reduction of ossification of parietal or frontal bones, and unossified interparietal bones) were observed at 80 mg/kg (maternally toxic dose), approximately 11 times the clinical exposure at the RHD, based on AUC. No treatment-related malformations were observed at up to 20 mg/kg, approximately 4 times the clinical exposure at the RHD, based on AUC. In a pre- and post-natal development study in mice, SC administration of atacicept-vymj once every two days (0, 5, 20, or 80 mg/kg) throughout pregnancy and lactation (GD 6 to lactation day 21) did not result in adverse effects on maternal function or development of offspring at up to 80 mg/kg, approximately 12 times the clinical exposure at the RHD based on AUC.

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

Clinical studies of TRUTAKNA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger adult patients. No clinically meaningful differences in the pharmacokinetics of TRUTAKNA were observed in patients aged 65 and over compared to younger adult patients.

Atacicept-vymj, a B-lymphocyte stimulator (Blys)-specific inhibitor and A Proliferation Inducing Ligand (APRIL) blocker, is a soluble recombinant fusion glycoprotein consisting of two parts: the extracellular ligand binding portion of the human transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) receptor and the Fc portion of human IgG1 (TACI Fc), which has been modified to reduce Fc receptor-mediated effector functions. Atacicept-vymj is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. The molecular weight of atacicept-vymj is 73.5 kDa (kilodaltons) based on the homodimeric form of the protein, which is composed of two identical monomers. TRUTAKNA (atacicept-vymj) injection is supplied as a sterile, preservative-free, clear to slightly opalescent, brownish yellow solution for subcutaneous injection. It is supplied in a 1 mL single-dose pre-filled autoinjector with a 27-gauge needle with a needle guard. Each 1 mL contains 150 mg of atacicept-vymj, 0.82 mg sodium acetate, 79.98 mg trehalose, and Water for Injection. Sodium hydroxide and acetic acid are included to adjust the pH to 5.0.

12.1 Mechanism of Action Atacicept-vymj, a BLyS-specific inhibitor and APRIL blocker, is a TACI-Fc fusion glycoprotein that binds B cell activating factor (BAFF) and APRIL with dissociation constants (Kd) of 106 pM and 33 pM, respectively, and reduces BAFF- and APRIL-mediated signaling. BAFF is also known as BlyS. Reduction in BAFF- and APRIL-mediated signaling decreases production of serum galactose deficient IgA1 (Gd-IgA1), which is implicated in the pathophysiology of IgAN.

12.2 Pharmacodynamics Immunoglobulins In IgAN patients treated with TRUTAKNA once weekly in the Origin 3 study, serum Gd-IgA1, Immunoglobulin A (IgA), Immunoglobulin G (IgG), and Immunoglobulin M (IgM) levels decreased within 4 weeks and these reductions were sustained through Week 36. By Week 36, mean serum levels were reduced from baseline by 68% for Gd-IgA1, 64% for IgA, 36% for IgG, and 75% for IgM.

12.3 Pharmacokinetics Absorption Following once weekly SC administration of TRUTAKNA 150 mg in IgAN patients, atacicept-vymj pharmacokinetics increased proportionally over a dose range of 75 to 150 mg. Steady state was achieved after approximately 24 weeks. Following the first SC dose, the maximum atacicept-vymj concentrations were reached approximately 36 hours after atacicept-vymj administration. Distribution Central and peripheral volume of distribution were 44 L and 61 L, respectively, in patients with IgAN. Metabolism/Elimination No drug metabolism studies have been conducted. Atacicept-vymj is a therapeutic protein that is expected to be catabolized into small peptides and amino acids by general catabolic degradation processes in multiple tissues. The estimated clearance of atacicept-vymj is 3.2 L/day, and the elimination half-life is approximately 40 days in IgAN patients. Specific Populations No clinically significant differences in the pharmacokinetics of atacicept-vymj were observed based on sex, age (18 to 74 years), weight (38.4 to 138 kg), race, and mild to severe renal impairment (eGFR: 22 to 89 mL/min).

12.6 Immunogenicity The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of ADA in the studies described below with the incidence of ADA in other studies, including those of TRUTAKNA. In a pooled analysis of phase 2 and phase 3 clinical data through Week 36 in patients with primary IgAN, 43.2% (60 of 139) of study subjects who were treated with TRUTAKNA once weekly developed ADA. There were no clinically significant effects of ADA on the pharmacokinetics, pharmacodynamics, safety or effectiveness of TRUTAKNA over the treatment duration of 36 weeks in these studies.

Atacicept-vymj, a BLyS-specific inhibitor and APRIL blocker, is a TACI-Fc fusion glycoprotein that binds B cell activating factor (BAFF) and APRIL with dissociation constants (Kd) of 106 pM and 33 pM, respectively, and reduces BAFF- and APRIL-mediated signaling. BAFF is also known as BlyS. Reduction in BAFF- and APRIL-mediated signaling decreases production of serum galactose deficient IgA1 (Gd-IgA1), which is implicated in the pathophysiology of IgAN.

Immunoglobulins In IgAN patients treated with TRUTAKNA once weekly in the Origin 3 study, serum Gd-IgA1, Immunoglobulin A (IgA), Immunoglobulin G (IgG), and Immunoglobulin M (IgM) levels decreased within 4 weeks and these reductions were sustained through Week 36. By Week 36, mean serum levels were reduced from baseline by 68% for Gd-IgA1, 64% for IgA, 36% for IgG, and 75% for IgM.

Absorption Following once weekly SC administration of TRUTAKNA 150 mg in IgAN patients, atacicept-vymj pharmacokinetics increased proportionally over a dose range of 75 to 150 mg. Steady state was achieved after approximately 24 weeks. Following the first SC dose, the maximum atacicept-vymj concentrations were reached approximately 36 hours after atacicept-vymj administration. Distribution Central and peripheral volume of distribution were 44 L and 61 L, respectively, in patients with IgAN. Metabolism/Elimination No drug metabolism studies have been conducted. Atacicept-vymj is a therapeutic protein that is expected to be catabolized into small peptides and amino acids by general catabolic degradation processes in multiple tissues. The estimated clearance of atacicept-vymj is 3.2 L/day, and the elimination half-life is approximately 40 days in IgAN patients. Specific Populations No clinically significant differences in the pharmacokinetics of atacicept-vymj were observed based on sex, age (18 to 74 years), weight (38.4 to 138 kg), race, and mild to severe renal impairment (eGFR: 22 to 89 mL/min).

, Mutagenesis, Impairment of Fertility Carcinogenesis No carcinogenicity studies have been conducted with atacicept-vymj. Mutagenesis Atacicept-vymj was not mutagenic or clastogenic in in vitro Ames, in vitro chromosomal aberration, and in vivo micronucleus assays. Impairment of Fertility No effects on male fertility were observed in mice dosed once every two days for 4 weeks prior to mating and throughout the mating period with SC atacicept-vymj up to 80 mg/kg, at exposures approximately 20 times the clinical exposure at the RHD, based on AUC. Increased pre- and post-implantation losses and reduced number of live fetuses were observed in female mice dosed with SC atacicept-vymj once every two days from 14 days prior to mating to GD 7 at ≥20 mg/kg, at exposures approximately 4 times the clinical exposure at the RHD, based on AUC.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ). Infections Inform patients that TRUTAKNA may decrease the ability of their immune system to fight infections. Advise patients to contact their healthcare provider if they develop signs or symptoms of infection [see Warnings and Precautions ( 5.1 )] Hypersensitivity and other Administration Reactions Advise patients to immediately seek medical attention for any signs and symptoms of hypersensitivity or systemic administration-related reactions. Inform patients that local injection-site reactions may occur and to report any severe reactions [see Contraindications ( 4 ) and Adverse Reactions ( 6.1 )] . Immunization Recommend that patients complete any required vaccinations prior to initiating treatment with TRUTAKNA. [see Warnings and Precautions ( 5.2 )] . Pregnancy Advise patients who are exposed to TRUTAKNA during pregnancy to contact 1-833-633-8372 [see Use in Specific Populations ( 8.1 )] . Disposal of Autoinjectors Advise patients to follow disposal procedures in the Instructions for Use. A puncture-resistant container for disposal of needles and syringes should be used. Instruct patients that they will need to follow their community guidelines for the correct way to dispose of their sharps disposal container. Instruct patients not to recycle their used sharps disposal container. Manufactured by: Vera Therapeutics, Inc. Brisbane, CA 94005 U.S. License No. 2386 TRUTAKNA™ is a trademark of Vera Therapeutics, Inc © 2026 Vera Therapeutics, Inc.

Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. If needed, TRUTAKNA autoinjector may be stored at room temperature up to 25°C (77°F), for a single period of 3 days (72 hours). Once TRUTAKNA has been stored at room temperature, it should not be placed back into the refrigerator. Discard the autoinjector if not used within this 72‑hour period. Do not freeze. Do not shake. Do not expose to heat.