Vabrinty

RECENT MAJOR CHANGES Warnings and Precautions ( 5.6 ) 02/2025 Dosage and Administration ( 2 ) 02/2025

1 INDICATIONS AND USAGE VABRINTY is indicated for the treatment of advanced prostate cancer. VABRINTY is a gonadotropin releasing hormone (GnRH) agonist indicated for the treatment of advanced prostate cancer. ( 1 )

2 DOSAGE AND ADMINISTRATION VABRINTY is administered subcutaneously based on the following recommended dose and schedule: 7.5 mg subcutaneously every month ( 2.1 ) 22.5 mg subcutaneously every 3 months ( 2.1 ) 30 mg subcutaneously every 4 months ( 2.1 ) 45 mg subcutaneously every 6 months ( 2.1 ) See Full Prescribing Information for preparation and administration instructions. ( 2.2 , 2.3 ) 2.1 Recommended Dosage VABRINTY is administered subcutaneously and provides continuous release of leuprolide acetate over a one-, three-, four-, or six-month treatment period (Table 1). VABRINTY must be administered by a healthcare provider. The injection delivers the dose of leuprolide acetate incorporated in a polymer formulation. Table 1. VABRINTY Recommended Dosing Dosage 7.5 mg 22.5 mg 30 mg 45 mg Recommended dose 1 injection every month 1 injection every 3 months 1 injection every 4 months 1 injection every 6 months As with other drugs administered by subcutaneous injection, the injection site should vary periodically. The specific injection location should be an area with sufficient soft or loose subcutaneous tissue. In clinical trials, the injections were administered in the upper- or mid-abdominal area. Avoid areas with brawny or fibrous subcutaneous tissue or locations that could be rubbed or compressed (i.e., with a belt or clothing waistband). In patients treated with GnRH analogues for prostate cancer, treatment is usually continued upon development of metastatic castration-resistant prostate cancer. 2.2 Preparation Instructions Use aseptic technique throughout the procedure. As with other similar agents, the use of gloves is recommended during mixing and administration. Allow the product to reach room temperature before mixing. Once mixed, the product must be administered within 30 minutes or it should be discarded. VABRINTY is packaged in a carton containing: Tray containing pre-connected syringe system and desiccant pack Prescribing information Sterile safety needle and cap (located under the tray in carton) Follow the detailed instructions below to ensure correct preparation of VABRINTY prior to administration: Step 1 On a clean field open the tray by tearing off the foil from the corner and remove the contents. Discard the desiccant pack. Remove the pre-connected syringe system from the tray. Open the sterile safety needle package by peeling back the paper tab. Note: Syringe A and Syringe B should not be lined-up yet. The product should only be administered with the co-packaged, sterile safety needle. Step 2 Grasp the latching button on the coupling device with your finger and thumb and press until you hear a snapping sound. The two syringes will be aligned. Do not bend the pre-connected syringe system. Step 3 Holding the syringes in a horizontal position, transfer the liquid contents of Syringe A into the leuprolide acetate powder contained in Syringe B. Thoroughly mix the product for 60 cycles by pushing the contents back and forth between both syringes to obtain a uniform suspension. A cycle is one push of the Syringe A plunger and one push of the Syringe B plunger. When thoroughly mixed, the suspension will appear light tan to tan (VABRINTY 7.5 mg) or colorless to pale yellow (VABRINTY 22.5 mg, 30 mg, and 45 mg). Note: Product must be mixed as described; shaking will NOT provide adequate mixing. Do not bend. Step 4 After mixing, hold the syringes vertically (upright) with Syringe B (wide syringe) on the bottom. The syringes should remain securely coupled. Transfer all of the mixed product into Syringe B by depressing the Syringe A plunger and slightly withdrawing the Syringe B plunger. Step 5 While ensuring the Syringe A plunger is fully pushed down, hold the coupling device and unscrew Syringe B. This will disconnect Syringe B from the coupling device. Syringe A will remain attached to the coupling device. Note: Small air bubbles will remain in the formulation – this is acceptable. Do not purge the air bubbles from Sy …

3 DOSAGE FORMS AND STRENGTHS VABRINTY is an injectable suspension of leuprolide acetate available in a pre-connected syringe system and packaged with a sterile safety needle and cap (Table 2), a desiccant, prescribing information and instructions for use. The pre-connected syringe system consists of syringe A and syringe B connected using a coupling device. Syringe A contains the in situ polymeric extended release technology and the syringe B contains leuprolide acetate powder. When reconstituted, VABRINTY is administered as a single dose. Refer to Table 10 for details of the description of the dosage form before and after mixing [see How Supplied/Storage and Handling ( 16 )] . Table 2. Specifications for VABRINTY Sterile Safety Needle and Cap VABRINTY strength Gauge Length 7.5 mg 20-gauge 5/8-inch 22.5 mg 20-gauge 5/8-inch 30 mg 20-gauge 5/8-inch 45 mg 18-gauge 5/8-inch Injectable suspension: 7.5 mg ( 3 ) Injectable suspension: 22.5 mg ( 3 ) Injectable suspension: 30 mg ( 3 ) Injectable suspension: 45 mg ( 3 )

4 CONTRAINDICATIONS Hypersensitivity VABRINTY is contraindicated in patients with hypersensitivity to GnRH, GnRH agonist analogs or any of the components of VABRINTY. Anaphylactic reactions to synthetic GnRH or GnRH agonist analogs have been reported in the literature. Known hypersensitivity to GnRH, GnRH agonist analogs or any of the components of VABRINTY ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Tumor Flare [see Warnings and Precautions ( 5.1 )] Hyperglycemia and Diabetes [see Warnings and Precautions ( 5.2 )] Cardiovascular Disease [see Warnings and Precautions ( 5.3 )] Effect on QT/QTc Interval [see Warnings and Precautions ( 5.4 )] Convulsions [see Warnings and Precautions ( 5.5 )] Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5. 6 )] Most common adverse reactions in clinical studies (incidence ≥ 5%): Malaise, fatigue, hot flashes/sweats, and testicular atrophy. ( 6.1 ) As with other GnRH agonists, other adverse reactions, including decreased bone density and rare cases of pituitary apoplexy have been reported. ( 6.1 , 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Uronova Pharmaceuticals, Inc. at 877-712-4575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial 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 all VABRINTY formulations was evaluated in clinical trials involving patients with advanced prostate cancer. In addition, the safety of VABRINTY 7.5 mg was evaluated in 8 surgically castrated males (Table 4). VABRINTY, like other GnRH analogs, caused a transient increase in serum testosterone concentrations during the first one to two weeks of treatment. Therefore, potential exacerbations of signs and symptoms of the disease during the first weeks of treatment are of concern in patients with vertebral metastases and/or urinary obstruction or hematuria. If these conditions are aggravated, it may lead to neurological problems such as weakness and/or paresthesia of the lower limbs or worsening of urinary symptoms [see Warnings and Precautions ( 5.7 )] . During the clinical trials, injection sites were closely monitored. Refer to Table 3 for a summary of reported injection site adverse reactions. Table 3. Reported Injection Site Adverse Reactions VABRINTY 7.5 mg 22.5 mg 30 mg 45 mg Study number AGL9904 AGL9909 AGL0001 AGL0205 Number of patients 120 117 90 111 Treatment 1 injection every month up to 6 months 1 injection every 3 months up to 6 months 1 injection every 4 months up to 8 months 1 injection every 6 months up to 12 months Number of injections 716 230 175 217 Transient burning/ stinging 248 (34.6%) injections; 84% reported as mild 50 (21.7%) injections; 86% reported as mild 35 (20%) injections; 100% reported as mild3 35 (16%) injections; 91.4% reported as mild Pain (generally brief and mild) 4.3% of injections (18.3% of patients) 3.5% of injections (6.0% of patients) 2.3% of injections2 (3.3% of patients) 4.6% of injections 4 Erythema (generally brief and mild) 2.6% of injections (12.5% of patients) 0.9% of injections 1 (1.7% of patients) 1.1% of injections (2.2% of patients) - Bruising (mild) 2.5% of injections (11.7% of patients) 1.7% of injections (3.4% of patients) - 2.3% of injections 5 Pruritus 1.4% of injections (9.2% of patients) 0.4% of injections (0.9% of patients) - - Induration 0.4% of injections (2.5% of patients) - - - Ulceration 0.1% of injections (> 0.8% of patients) - - - Erythema was reported following 2 injections of VABRINTY 22.5 mg. One report characterized the erythema as mild and it resolved within 7 days. The other report characterized the erythema as moderate and it resolved within 15 days. Neither patient experienced erythema at multiple injection times. A single reaction reported as moderate pain resolved within two minutes and all 3 mild pain reactions resolved within several days following injection of VABRINTY 30 mg. Following injection of VABRINTY 30 mg, three of the 35 burning/stinging reactions were reported as moderate. Transient pain was reported as mild in intensity in nine of …

8 USE IN SPECIFIC POPULATIONS Females and males of reproductive potential: VABRINTY may impair fertility. ( 8.3 ) Pediatric: Safety and effectiveness in pediatric patients have not been established. ( 8.4 ) Geriatric: This label reflects clinical trials for VABRINTY in prostate cancer where the majority of subjects were at least 65 years of age ( 8.5 ). 8.1 Pregnancy Risk Summary Based on findings in animal studies and mechanism of action, VABRINTY may cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data in pregnant women to inform the drug-associated risk. Expected hormonal changes that occur with VABRINTY treatment increase the risk for pregnancy loss. In animal developmental and reproductive studies, major fetal abnormalities were observed after administration of leuprolide acetate throughout gestation in rats. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus (see Data) . Data Animal Data In animal developmental and reproductive studies, major fetal abnormalities were observed after administration of leuprolide acetate throughout gestation. There were increased fetal mortality and decreased fetal weights in rats and rabbits. The effects of fetal mortality are expected consequences of the alterations in hormonal levels brought about by this drug. 8.2 Lactation The safety and efficacy of VABRINTY have not been established in females. There is no information regarding the presence of VABRINTY in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in a breastfed child from VABRINTY, a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. 8.3 Females and Males of Reproductive Potential Infertility Males Based on mechanism of action, VABRINTY may impair fertility in males of reproductive potential [see Clinical Pharmacology ( 12.1 )] . 8.4 Pediatric Use The safety and effectiveness of VABRINTY in pediatric patients have not been established. 8.5 Geriatric Use The majority of the patients (approximately 70%) studied in the clinical trials were age 70 and older. Clinical studies of VABRINTY did not include sufficient numbers of younger adult patients to determine if patients 65 years of age and older respond differently than younger adult patients.

12.1 Mechanism of Action Leuprolide acetate, a gonadotropin releasing hormone (GnRH) agonist, acts as an inhibitor of gonadotropin secretion when given continuously in therapeutic doses. Animal and human studies indicate that after an initial stimulation, chronic administration of leuprolide acetate results in suppression of testicular and ovarian steroidogenesis. This effect is reversible upon discontinuation of drug therapy.

11 DESCRIPTION VABRINTY is a sterile polymeric matrix formulation of leuprolide acetate, a GnRH agonist, for subcutaneous injection. It is designed to deliver leuprolide acetate at a controlled rate over a one-, three-, four, or six-month therapeutic period. Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin releasing hormone (GnRH) that, when given continuously, inhibits pituitary gonadotropin secretion and suppresses testicular and ovarian steroidogenesis. The analog possesses greater potency than the natural hormone. The chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide acetate (salt) with the following structural formula: VABRINTY is supplied as a pre-connected syringe system comprised of two prefilled syringes (syringe A and syringe B) connected using a coupling device. Immediately prior to administration, the contents of the pre-connected syringe system are mixed until homogenous. VABRINTY is administered subcutaneously, where it forms a solid drug delivery depot. Syringe A contains the in situ polymeric extended release technology consisting of a biodegradable poly (DL-lactide-co-glycolide) (PLGH or PLG) polymer formulation dissolved in a biocompatible solvent, N -methyl-2-pyrrolidone (NMP) and syringe B contains leuprolide acetate. Refer to Table 5 for the delivery system composition and reconstituted product formulation for each VABRINTY product. Table 5. VABRINTY Delivery System Composition and Reconstituted Product Formulation VABRINTY 7.5 mg 22.5 mg 30 mg 45 mg In situ polymeric extended release technology Polymer PLGH PLG PLG PLG Polymer description Copolymer containing carboxyl endgroups Copolymer with hexanediol Copolymer with hexanediol Copolymer with hexanediol Polymer DL-lactide to glycolide molar ratio 50:50 75:25 75:25 85:15 Reconstituted product Polymer delivered 82.5 mg 158.6 mg 211.5 mg 165 mg NMP delivered 160.0 mg 193.9 mg 258.5 mg 165 mg Leuprolide acetate delivered 7.5 mg 22.5 mg 30 mg 45 mg Approximate Leuprolide free base equivalent 7.0 mg 21 mg 28 mg 42 mg Approximate administered formulation weight 250 mg 375 mg 500 mg 375 mg Approximate injection volume 0.25 mL 0.375 mL 0.5 mL 0.375 mL structure

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied VABRINTY is supplied as a single-dose, two syringe-mixing system with a sterile safety needle and cap. VABRINTY is available as follows (Table 10): Table 10. VABRINTY Product Presentations VABRINTY strength NDC number Description of Syringe A with the delivery system Description of Syringe B with leuprolide acetate Description of the suspension after mixing 7.5 mg 85043-075-05 Light tan to tan, clear, viscous solution White to off white powder Light tan to tan 22.5 mg 85043-025-02 Colorless to pale yellow, clear viscous solution White to off white powder Colorless to pale yellow 30 mg 85043-030-03 Colorless to pale yellow, clear viscous solution White to off white powder Colorless to pale yellow 45 mg 85043-045-04 Colorless to pale yellow, clear viscous solution White to off white powder Colorless to pale yellow Storage Store at 2°C to 8°C (36°F to 46°F) Once outside the refrigerator this product may be stored in its original packaging at room temperature 15°C to 30°C (59°F to 86°F) for up to eight weeks prior to mixing and administration.