Romosozumab-aqqg is a humanized monoclonal antibody (IgG2) produced in a mammalian cell line (Chinese Hamster Ovary) by recombinant DNA technology that binds to and inhibits sclerostin. Romosozumab-aqqg has an approximate molecular weight of 149 kDa. EVENITY (romosozumab-aqqg) injection is supplied as a sterile, preservative-free, clear to opalescent, colorless to light yellow solution for subcutaneous injection in a single-use prefilled syringe. Two 105 mg/1.17 mL single-use prefilled syringes are required to administer the recommended 210 mg dose of EVENITY . Each single-use prefilled syringe delivers 1.17 mL of solution containing 105 mg of romosozumab-aqqg, acetate (3.8 mg), calcium (0.61 mg), polysorbate 20 (0.07 mg) and sucrose (70 mg) in Water for Injection, USP, and sodium hydroxide to a pH of 5.2.

EVENITY is a sclerostin inhibitor indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy. Limitations of Use: Limit duration of use to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an anti-resorptive agent should be considered

Treatment of Postmenopausal Women with Osteoporosis at High Risk for Fracture EVENITY is indicated for the treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as a history of osteoporotic fracture, or multiple risk factors for fracture; or patients who have failed or are intolerant to other available osteoporosis therapy

Limitations of Use The anabolic effect of EVENITY wanes after 12 monthly doses of therapy. Therefore, the duration of EVENITY use should be limited to 12 monthly doses. If osteoporosis therapy remains warranted, continued therapy with an anti-resorptive agent should be considered .

Injection: 105 mg/1.17 mL clear to opalescent, colorless to light yellow solution in a single-use prefilled syringe. A full dose of EVENITY requires two single-use prefilled syringes. Injection: 105 mg/1.17 mL solution in a single-use prefilled syringe. A full dose of EVENITY requires two single-use prefilled syringes.

Two separate subcutaneous injections are needed to administer the total dose of 210 mg. Inject two syringes, one after the other. Should be administered by a healthcare provider. Administer 210 mg subcutaneously once every month for 12 doses in the abdomen, thigh, or upper arm. Adequately supplement calcium and vitamin D during treatment

Important Dosage and Administration Instructions Two separate syringes (and two separate subcutaneous injections) are needed to administer the total dose of 210 mg of EVENITY. Inject two 105 mg/1.17 mL prefilled syringes, one after the other. EVENITY should be administered by a healthcare provider

Recommended Dosage The recommended dose of EVENITY is 210 mg administered subcutaneously in the abdomen, thigh or upper arm. Administer EVENITY once every month. The treatment duration for EVENITY is 12 monthly doses. Patients should be adequately supplemented with calcium and vitamin D during treatment with EVENITY . If the EVENITY dose is missed, administer as soon as it can be rescheduled. Thereafter, EVENITY can be scheduled every month from the date of the last dose

Preparation and Administration Instructions Administration instructions: Prefilled syringe with automatic needle guard: Step 1: Prior to Administration: Remove two syringes from the carton. Visually inspect EVENITY for particles and discoloration prior to administration. EVENITY is a clear to opalescent, colorless to light yellow solution. Do not use if the solution is cloudy or discolored or contains particles. Do not use the syringe if any part appears cracked or broken the gray needle cap is missing or not securely attached the expiration date printed on the label has passed the syringe has been dropped on a hard surface Always hold the syringe by the syringe body to remove the syringe from the tray. See Figure A . Do not grasp the plunger rod. Do not grasp the gray needle cap. Do not remove the gray needle cap until you are ready to inject. Allow EVENITY to sit at room temperature for at least 30 minutes before injecting. Do not warm in any other way . Figure A Step 2: Select the Injection Site and Prepare the Syringe Prepare and clean two injection sites, one for each of the two injections. See Figure B . Figure B The recommended subcutaneous injection sites include: The thigh Abdomen, except for a two-inch area right around the navel Outer area of upper arm Clean the injection sites with alcohol wipes. Let the skin dry. Choose a different site each time you give an injection. If you want to use the same injection site, make sure it is not the same spot on the injection site you used for a previous injection. Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks. Choose the first syringe. Pull the gray needle cap straight off and away from your body when you are ready to inject. See Figure C . Figure C Do not put the gray needle cap back onto the syringe. Do not leave the cap off for more than 5 minutes as this can dry out the solution. The prefilled syringe may contain air bubbles. Do not try to push air bubbles out as it is normal to see air bubbles. Step 3: Inject EVENITY Pinch the skin around the injection site before injecting. Insert the needle into the pinched skin at or about a 45-degree angle. Slowly press the plunger head all the way down with your thumb until it is completely between the needle guard clips. Do not pull back on the plunger rod at any time. Do not remove the syringe until all the medicine has been injected. Do not administer into muscle or blood vessel. See Figure D . Figure D Slowly release pressure on the plunger head with your thumb and remove the syringe from the skin. Let go of the skin after the needle is removed. Releasing the plunger head covers the used needle. See Figure E . Figure E Step 4: Syringe and Gray Needle Cap Disposal Immediately dispose of the syringe and needle cap in the nearest sharps container. Important: Repeat all steps with the second syringe to inject the full dose. Figure A Figure B Figure C Figure D Figure E Administration instructions: Prefilled syringe : Step 1: Prior to Administration: Remove two syringes from the carton. Visually inspect EVENITY for particles and discoloration prior to administration. EVENITY is a clear to opalescent, colorless to light yellow solution. Do not use if the solution is cloudy or discolored or contains particles. Do not use the syringe if any part appears cracked or broken the gray needle cap is missing or not securely attached the expiration date printed on the label has passed the syringe has been dropped on a hard surface Always hold the prefilled syringe by the syringe barrel to remove the syringe from the tray. See Figure F . Do not grasp the plunger rod. Do not grasp the gray needle cap. Do not remove the gray needle cap until you are ready to inject. Allow EVENITY to sit at room temperature for at least 30 minutes before injecting. Do not warm in any other way . Figure F Step 2: Select the Injection Site and Prepare the Syringe Prepare and clean two injection sites, one for each of the two injections. See Figure G . Figure G The recommended subcutaneous injection sites include: The thigh Abdomen, except for a two-inch area right around the navel Outer area of upper arm Clean the injection sites with alcohol wipes. Let the skin dry. Choose a different site each time you give an injection. If you want to use the same injection site, make sure it is not the same spot on the injection site you used for a previous injection. Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks. Choose the first syringe. Pull the gray needle cap straight off and away from your body when you are ready to inject. See Figure H . Figure H Do not put the gray needle cap back onto the syringe. Do not leave the cap off for more than 5 minutes as this can dry out the solution. The prefilled syringe may contain air bubbles. Do not try to push air bubbles out as it is normal to see air bubbles. Step 3: Inject EVENITY Pinch the skin around the injection site before injecting. Insert the needle into the pinched skin at or about a 45-degree angle. Insert needle and inject all the liquid subcutaneously. Do not administer into muscle or blood vessel. See Figure I . Figure I When done, gently lift the syringe off of the skin. Step 4: Syringe and Needle Cap Disposal Immediately dispose of the syringe and needle cap in the nearest sharps container. Important: Repeat all steps with the second syringe to inject the full dose. Figure A Figure B Figure C Figure D

Major Adverse Cardiac Events (MACE): Monitor for symptoms of MI and stroke and seek prompt medical attention if symptoms occur. Hypersensitivity: Hypersensitivity reactions, including angioedema, erythema multiforme, dermatitis, rash, and urticaria. Discontinue EVENITY if a clinically significant allergic reaction occurs. Hypocalcemia: Adequately supplement calcium and vitamin D during treatment with EVENITY. Osteonecrosis of the Jaw: Monitor for symptoms. Consider discontinuation of therapy based on benefit-risk assessment. Atypical Femoral Fracture: Evaluate new or unusual thigh, hip, or groin pain to rule out an incomplete femur fracture. 5.1 Major Adverse Cardiac Events (MACE) In a randomized controlled trial in postmenopausal women, there was a higher rate of major adverse cardiac events (MACE), a composite endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke, in patients treated with EVENITY compared to those treated with alendronate . EVENITY should not be initiated in patients who have had a myocardial infarction or stroke within the preceding year. Consider whether the benefits outweigh the risks in patients with other cardiovascular risk factors. Monitor for signs and symptoms of myocardial infarction and stroke and instruct patients to seek prompt medical attention if symptoms occur. If a patient experiences a myocardial infarction or stroke during therapy, EVENITY should be discontinued

Hypersensitivity Reactions Hypersensitivity reactions, including angioedema, erythema multiforme, dermatitis, rash, and urticaria have occurred in EVENITY-treated patients. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue further use of EVENITY

Hypocalcemia Hypocalcemia has occurred in patients receiving EVENITY. Correct hypocalcemia prior to initiating EVENITY . Monitor patients for signs and symptoms of hypocalcemia. Patients should be adequately supplemented with calcium and vitamin D while on EVENITY . Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] 15 to 29 mL/min/1.73 m 2 ) or receiving dialysis are at greater risk of developing hypocalcemia. Monitor serum calcium and adequately supplement patients who have severe renal impairment or are receiving dialysis with calcium and vitamin D. Instruct patients with severe renal impairment, including those receiving dialysis, about the symptoms of hypocalcemia and the importance of maintaining calcium levels with adequate calcium and vitamin D supplementation

Osteonecrosis of the Jaw Osteonecrosis of the jaw (ONJ), which can occur spontaneously, is generally associated with tooth extraction and/or local infection with delayed healing, and has been reported in patients receiving EVENITY. A routine oral examination should be performed by the prescriber prior to initiation of EVENITY treatment. Concomitant administration of drugs associated with ONJ (chemotherapy, bisphosphonates, denosumab, angiogenesis inhibitors, and corticosteroids) may increase the risk of developing ONJ. Other risk factors for ONJ include cancer, radiotherapy, poor oral hygiene, pre-existing dental disease or infection, anemia, and coagulopathy . For patients requiring invasive dental procedures, clinical judgment of the treating physician and/or oral surgeon should guide the management plan of each patient based on benefit-risk assessment. Patients who are suspected of having or who develop ONJ while on EVENITY should receive care by a dentist or an oral surgeon. In these patients, dental surgery to treat ONJ may exacerbate the condition. Discontinuation of EVENITY should be considered based on benefit-risk assessment

Atypical Subtrochanteric and Diaphyseal Femoral Fractures Atypical low-energy or low trauma fractures of the femoral shaft have been reported in patients receiving EVENITY . These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated. Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. During EVENITY treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Patient presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of EVENITY therapy should be considered based on benefit-risk assessment .