SUNLENCA

SUNLENCA tablets and SUNLENCA injection contain lenacapavir sodium, a capsid inhibitor. The chemical name of lenacapavir sodium is: Sodium (4-chloro-7-(2-(( S )-1-(2-((3b S ,4a R )-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1 H -cyclopropa[3,4]cyclopenta[1,2- c ]pyrazol-1-yl)acetamido)-2-(3,5-difluorophenyl)ethyl)-6-(3-methyl-3-(methylsulfonyl)but-1-yn-1-yl)pyridin-3-yl)-1-(2,2,2-trifluoroethyl)-1 H -indazol-3-yl)(methylsulfonyl)amide. Lenacapavir sodium has a molecular formula of C 39 H 31 ClF 10 N 7 NaO 5 S 2, a molecular weight of 990.3, and the following structural formula: Lenacapavir sodium is a light yellow to yellow solid and is practically insoluble in water. Chemical Structure SUNLENCA tablets are for oral administration. Each film-coated tablet contains 300 mg of lenacapavir (present as 306.8 mg lenacapavir sodium) and the following inactive ingredients: copovidone, croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, and poloxamer 407. The tablets are film-coated with a coating material containing iron oxide black, iron oxide red, iron oxide yellow, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. SUNLENCA injection is for subcutaneous administration. Each single-dose vial contains 463.5 mg/1.5 mL (309 mg/mL) of lenacapavir (present as 473.1 mg/1.5 mL of lenacapavir sodium) as a sterile, preservative-free, clear, yellow solution and the following inactive ingredients: 896.3 mg of polyethylene glycol 300 (as solvent) and water for injection. The apparent pH range of the injection is 9.0–10.2. The vial stoppers are not made with natural rubber latex.

SUNLENCA, in combination with other antiretroviral(s), is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug resistant HIV-1 whose current antiretroviral regimen is failing due to resistance, intolerance, or safety considerations. SUNLENCA, a human immunodeficiency virus type 1 (HIV-1) capsid inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-1 whose current antiretroviral regimen is failing due to resistance, intolerance, or safety considerations. ( 1 )

Recommended dosage – Initiation with one of two options followed by once every 6 months maintenance injection dosing. Tablets may be taken without regard to food. ( 2.2 ) Initiation Option 1 Day 1 927 mg by subcutaneous injection (2 × 1.5 mL injections) 600 mg orally (2 × 300 mg tablets) Day 2 600 mg orally (2 × 300 mg tablets) Initiation Option 2 Day 1 600 mg orally (2 × 300 mg tablets) Day 2 600 mg orally (2 × 300 mg tablets) Day 8 300 mg orally (1 × 300 mg tablet) Day 15 927 mg by subcutaneous injection (2 × 1.5 mL injections) Maintenance 927 mg by subcutaneous injection (2 × 1.5 mL injections) every 6 months (26 weeks) from the date of the last injection +/-2 weeks. Planned missed injections: If scheduled injection is to be missed by more than 2 weeks, SUNLENCA tablets may be used for oral bridging for up to 6 months until injections resume. Recommended dosage is 300 mg orally once every 7 days. ( 2.3 ) Unplanned missed injections: If more than 28 weeks since last injection and tablets have not been taken for oral bridging, restart initiation from Day 1 (using Option 1 or Option 2) if clinically appropriate. ( 2.3 ) SUNLENCA injection is for subcutaneous administration only. Two 1.5 mL injections are required for complete dose. ( 2.4 ) 2.1 Adherence to Treatment Regimen Prior to starting SUNLENCA, healthcare providers should carefully select patients who agree to the required every 6 month injection dosing schedule and counsel patients about the importance of adherence to scheduled SUNLENCA dosing visits and concomitant oral antiretroviral therapy to help maintain viral suppression and reduce the risk of viral rebound and potential development of resistance with missed doses [see Warnings and Precautions (5.2) , Microbiology (12.4) ] . 2.2 Recommended Dosage SUNLENCA can be initiated using one of the two recommended dosage regimens in Table 1 and Table 2 below. Maintenance dosing is administered by subcutaneous injection every 6 months regardless of the initiation regimen. Healthcare providers should determine the appropriate initiation regimen for the patient. SUNLENCA oral tablets may be taken with or without food [see Clinical Pharmacology (12.3) ] . Table 1 Recommended Treatment Regimen for SUNLENCA Initiation and Maintenance, Option 1 Treatment Time Dosage of SUNLENCA: Initiation Day 1 927 mg by subcutaneous injection (2 × 1.5 mL injections) 600 mg orally (2 × 300 mg tablets) Day 2 600 mg orally (2 × 300 mg tablets) Dosage of SUNLENCA: Maintenance Every 6 months (26 weeks) From the date of the last injection. +/-2 weeks 927 mg by subcutaneous injection (2 × 1.5 mL injections) Table 2 Recommended Treatment Regimen for SUNLENCA Initiation and Maintenance, Option 2 Treatment Time Dosage of SUNLENCA: Initiation Day 1 600 mg orally (2 × 300 mg tablets) Day 2 600 mg orally (2 × 300 mg tablets) Day 8 300 mg orally (1 × 300 mg tablet) Day 15 927 mg by subcutaneous injection (2 × 1.5 mL injections) Dosage of SUNLENCA: Maintenance Every 6 months (26 weeks) From the date of the last injection. +/-2 weeks 927 mg by subcutaneous injection (2 × 1.5 mL injections) 2.3 Recommended Dosing Schedule for Missed Dose Planned Missed Injections During the maintenance period, if a patient plans to miss a scheduled 6-month injection visit by more than 2 weeks, SUNLENCA tablets may be taken for up to 6 months until injections resume. Refer to Table 3 below for the recommended dosage after planned missed injections. Table 3 Recommended Dosage after Planned Missed Injections: Weekly Oral Maintenance Time since Last Injection Recommendation 26 to 28 weeks Maintenance oral dosage of 300 mg taken once every 7 days for up to 6 months. Resume the maintenance injection dosage within 7 days after the last oral dose. Unplanned Missed Injections Patients who miss a scheduled injection visit should be clinically reassessed, including consideration of lenacapavir resistance testing, to ensure resumption of therapy remains appropriate. During the maintenance period, if more than 28 weeks have elapsed since the last injection and SUNLENCA tablets have not been taken, see Table 4 below for the recommended dosage after unplanned missed injections. Adherence to the injection dosing schedule is strongly recommended [see Dosage and Administration (2.1) and Microbiology (12.4) ] . Table 4 Recommended Dosage after Unplanned Missed Injections Time since Last Injection Recommendation More than 28 weeks Reinitiate with Option 1 (Table 1) or Option 2 (Table 2) and then continue with maintenance injection dosing. 2.4 Preparation and Administration of Subcutaneous Injection SUNLENCA injection is only for subcutaneous administration into the abdomen by a healthcare provider. Do NOT administer intradermally due to risk of serious injection site reactions [see Warnings and Precautions (5.3) ]. Use aseptic technique. Visually inspect the solution in the vials and prepared syringe for particulate matter and discoloration prior to administration. SUNLENCA injection is a yellow solution. Do not use SUNLENCA injection if the solution is discolored or if it contains particulate matter. Once the solution is withdrawn from the vials, the subcutaneous injections should be administered as soon as possible [see How Supplied/Storage and Handling (16) ]. There are two available injection kits, which differ only in how SUNLENCA injection is prepared (the components and associated method for withdrawal of the solution from the vials) [see How Supplied/Storage and Handling (16) ] . Refer to the figures below for the relevant injection kit. The injection kit components are for single use only. Two 1.5 mL injections are required for a complete dose. Vial access device injection kit Figure 1 identifies the components for use in the administration steps for the vial access device injection kit, and the administration steps are provided in Figure 2. Use of a vial access device is required in this kit. Figure 1 SUNLENCA Vial Access Device Injection Kit Components Figure 2 SUNLENCA Injection Steps for Vial Access Device Injection Kit Withdrawal needle injection kit Figure 3 identifies the components for use in the administration steps for the withdrawal needle injection kit, and the administration steps are provided in Figure 4. The 18-gauge needle is for withdrawal only in this kit. Figure 3 SUNLENCA Withdrawal Needle Injection Kit Components Figure 4 SUNLENCA Injection Steps for Withdrawal Needle Injection Kit Figure 1 Figure 2 Figure 3 Figure 4

Concomitant administration of SUNLENCA with strong CYP3A inducers is contraindicated due to decreased lenacapavir plasma concentrations, which may result in the loss of therapeutic effect and development of resistance to SUNLENCA [see Drug Interactions (7.1) ] . Concomitant administration of SUNLENCA is contraindicated with strong CYP3A inducers. ( 4 )

The following adverse reactions are discussed in other sections of the labeling: Immune Reconstitution Syndrome [see Warnings and Precautions (5.1) ] Injection Site Reactions [see Warnings and Precautions (5.3) ]. Most common adverse reactions (incidence greater than or equal to 3%, all grades) are nausea and injection site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 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 primary safety assessment of SUNLENCA was based on data from heavily treatment-experienced adult participants with HIV who received SUNLENCA in a Phase 2/3 trial (CAPELLA; N=72) through Week 52 (median duration on study of 71 weeks) [see Clinical Studies (14) ] , as well as supportive data in treatment-naïve adult participants with HIV who received SUNLENCA in a Phase 2 trial (CALIBRATE; N=157) through Week 54 (median duration of exposure of 66 weeks). The most common adverse reactions (all Grades) reported in at least 3% of participants in CAPELLA were nausea and injection site reactions. The proportion of partcipants in CAPELLA who discontinued treatment with SUNLENCA due to adverse events, regardless of severity, was 1% (Grade 1 injection site nodule in 1 participant). Table 3 displays the frequency of adverse reactions (all Grades) greater than or equal to 3% in the SUNLENCA group. Table 3 Adverse Reactions (All Grades) Reported in ≥ 3% Frequencies of adverse reactions are based on all adverse events attributed to trial drug by the investigator, based on all participants (cohorts 1 and 2) in CAPELLA. of Heavily Treatment Experienced Adults with HIV-1 Receiving SUNLENCA in CAPELLA (Week 52 Analysis) Adverse Reactions SUNLENCA + Background Regimen (N=72) Injection Site Reactions 65% Nausea 4% The majority (96%) of all adverse reactions associated with SUNLENCA were mild or moderate in severity. Injection-Associated Adverse Reactions Local Injection Site Reactions (ISRs) : The most frequent adverse reactions were ISRs. Of the 72 participants in CAPELLA, 65% had experienced an ISR attributed to study drug through at least the Week 52 visit. Most participants had mild (Grade 1, 44%) or moderate (Grade 2, 17%) ISRs. Four percent of participants experienced a severe (Grade 3) ISR (erythema, pain, swelling) that resolved within 15 days. The ISRs reported in more than 1% of participants were swelling (36%), pain (31%), erythema (31%), nodule (25%), induration (15%), pruritus (6%), extravasation (3%) and mass (3%). ISRs reported in 1% of participants included discomfort, hematoma, edema, and ulcer. Nodules and indurations at the injection site took longer to resolve than other ISRs. The median time to resolution of all ISRs, excluding nodules and indurations, was 5 days (range: 1 to 183). The median time to resolution of nodules and indurations associated with the first injections of SUNLENCA was 148 (range: 41 to 727) and 70 (range: 3 to 252) days, respectively. After a median follow up of 553 days, 30% of nodules and 13% of indurations (in 10% and 1% of participants, respectively) associated with the first injections of SUNLENCA had not fully resolved. Qualitative descriptions of injection site nodules and indurations were not routinely reported, but, where reported, the majority of injection site nodules and indurations were palpable but not visible. Measurements of injection site nodules and indurations were not routinely performed or standardized, but where measurements were reported, the maximum size for the majority of injection site nodules and indurations was approximately 1 to 4 cm [see Warnings and Precautions (5.3) ] . Laboratory Abnormalities The frequency of laboratory abnormalities (Grades 3 to 4) occurring in at least 2% of participants in CAPELLA are presented in Table 4. A causal association between SUNLENCA and these laboratory abnormalities has not been established. Table 4 Selected Laboratory Abnormalities (Grades 3 to 4) Reported in ≥ 2% of Participants Receiving SUNLENCA in CAPELLA (Week 52 Analysis) Laboratory Parameter Abnormality SUNLENCA + Background Regimen (N=72) Frequencies are based on treatment-emergent laboratory abnormalities in all participants (cohorts 1 and 2) in CAPELLA. Percentages were calculated based on the number of participants with post-baseline toxicity grades for each laboratory parameter (n=72 for all parameters except hyperglycemia fasting n=57). ALT= alanine aminotransferase; AST= aspartate aminotransferase; ULN = upper limit of normal Creatinine ( >1.8 × ULN or ≥1.5 × baseline) 13% Glycosuria (>2+) Grade 3 only (no Grade 4 values reported). 6% Hyperglycemia (fasting) (>250 mg/dL) 5% Proteinuria (>2+) 4% ALT (≥5 × ULN) 3% AST (≥5 × ULN) 3% Direct Bilirubin (>ULN) 3% 6.2 Postmarketing Experience In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postmarketing use. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General disorders and administration site conditions Injection site necrosis [see Warnings and Precautions (5.3) ] .

Consult the Full Prescribing Information prior to and during treatment for important drug interactions. ( 4 , 7 , 12.3 ) 7.1 Effect of Other Drugs on SUNLENCA Lenacapavir is a substrate of P-gp, UGT1A1, and CYP3A. Strong or Moderate CYP3A Inducers Drugs that are strong or moderate inducers of CYP3A may significantly decrease plasma concentrations of lenacapavir [see Clinical Pharmacology (12.3) ] , which may result in loss of therapeutic effect of SUNLENCA and development of resistance. Concomitant administration of SUNLENCA with strong CYP3A inducers during SUNLENCA treatment is contraindicated [see Contraindications (4) ] . Concomitant administration of SUNLENCA with moderate CYP3A inducers during SUNLENCA treatment is not recommended. Combined P-gp, UGT1A1, and Strong CYP3A Inhibitors Combined P-gp, UGT1A1, and strong CYP3A inhibitors may significantly increase plasma concentrations of SUNLENCA. Concomitant administration of SUNLENCA with these inhibitors is not recommended. 7.2 Effect of SUNLENCA on Other Drugs Lenacapavir is a moderate inhibitor of CYP3A. Due to the long half-life of lenacapavir following subcutaneous administration, SUNLENCA may increase the exposure of drugs primarily metabolized by CYP3A [see Clinical Pharmacology (12.3) ] initiated within 9 months after the last subcutaneous dose of SUNLENCA, which may increase the potential risk of adverse reactions. See the prescribing information of the sensitive CYP3A substrate for dosing recommendations with moderate inhibitors of CYP3A. 7.3 Established and Other Potentially Significant Drug Interactions Table 5 provides a listing of clinically significant drug interactions with recommended prevention or management strategies, but is not all inclusive. The drug interactions described are based on studies conducted with SUNLENCA or are drug interactions that may occur with SUNLENCA [see Contraindications (4) and Clinical Pharmacology (12.3) ] . Table 5 Drug Interactions with SUNLENCA Concomitant Drug Class: Drug Name Effect on Concentration ↑ = Increase, ↓ = Decrease. Clinical Comment Antiarrhythmics: digoxin ↑ digoxin Use with caution and monitor digoxin therapeutic concentration. Anticoagulants: Direct Oral Anticoagulants (DOACs) rivaroxaban dabigatran edoxaban ↑ DOAC Refer to the DOAC prescribing information for concomitant administration with moderate CYP3A inhibitors and/or P-gp inhibitors. Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin ↓ lenacapavir Concomitant administration of carbamazepine, oxcarbazepine, phenobarbital, or phenytoin may result in loss of therapeutic effect and development of resistance. Concomitant administration of SUNLENCA with carbamazepine or phenytoin is contraindicated. Concomitant administration of SUNLENCA with oxcarbazepine or phenobarbital is not recommended. Consider use of alternative anticonvulsants. Antiretroviral Agents: atazanavir/cobicistat Drug-drug interaction study was conducted. atazanavir/ritonavir ↑ lenacapavir (atazanavir/cobicistat, atazanavir/ritonavir) Concomitant administration of efavirenz, nevirapine, or tipranavir/ritonavir may result in loss of therapeutic effect and development of resistance. efavirenz nevirapine tipranavir/ritonavir ↓ lenacapavir (efavirenz, nevirapine, tipranavir/ritonavir) Concomitant administration with atazanavir/cobicistat, atazanavir/ritonavir, efavirenz, nevirapine, or tipranavir/ritonavir is not recommended. Antimycobacterials: rifabutin rifampin rifapentine ↓ lenacapavir Concomitant administration of rifabutin, rifampin and rifapentine may result in loss of therapeutic effect and development of resistance. Concomitant administration of SUNLENCA with rifampin is contraindicated [see Contraindications (4) ] . Concomitant administration of SUNLENCA with rifabutin or rifapentine is not recommended. Corticosteroids (systemic): cortisone/hydrocortisone dexamethasone ↑ corticosteroids (systemic) Concomitant administration with systemic corticosteroids whose exposures are significantly increased by CYP3A inhibitors can increase the risk for Cushing's syndrome and adrenal suppression. Initiate with the lowest starting dose and titrate carefully while monitoring for safety. ↓ lenacapavir (dexamethasone) Concomitant administration of systemic dexamethasone may result in loss of therapeutic effect of lenacapavir and development of resistance. Alternative corticosteroids to dexamethasone should be considered, particularly for long-term use. Ergot derivatives: dihydroergotamine ergotamine methylergonovine ↑ dihydroergotamine ↑ ergotamine ↑ methylergonovine Concomitant administration of SUNLENCA with dihydroergotamine, ergotamine or methylergonovine is not recommended. Herbal Products: St. John's wort The induction potency of St. John's wort may vary widely based on preparation. (Hypericum perforatum) ↓ lenacapavir Concomitant administration of St. John's wort may result in loss of therapeutic effect and development of resistance. Concomitant administration of SUNLENCA with St. John's wort is contraindicated. HMG-CoA Reductase Inhibitors: lovastatin simvastatin ↑ lovastatin ↑ simvastatin Initiate lovastatin and simvastatin with the lowest starting dose and titrate carefully while monitoring for safety (e.g., myopathy). Narcotic analgesics metabolized by CYP3A: e.g., fentanyl, oxycodone ↑ fentanyl ↑ oxycodone Careful monitoring of therapeutic effects and adverse reactions associated with CYP3A-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with co-administration. tramadol ↑ tramadol A decrease in dose may be needed for tramadol with concomitant use. Narcotic analgesic for treatment of opioid dependence: buprenorphine, methadone buprenorphine: effects unknown methadone: effects unknown Initiation of buprenorphine or methadone in patients taking SUNLENCA: Carefully titrate the dose of buprenorphine or methadone to the desired effect; use the lowest feasible initial or maintenance dose. Initiation of SUNLENCA in patients taking buprenorphine or methadone: A dose adjustment for buprenorphine or methadone may be needed. Monitor clinical signs and symptoms. Opioid Antagonist: naloxegol ↑ naloxegol Avoid use with SUNLENCA; if unavoidable, decrease the dosage of naloxegol and monitor for adverse reactions. Phosphodiesterase-5 (PDE-5) Inhibitors: sildenafil tadalafil vardenafil ↑ PDE-5 inhibitors Use of PDE-5 inhibitors for pulmonary arterial hypertension (PAH): Concomitant administration of SUNLENCA with tadalafil for the treatment of PAH is not recommended. Use of PDE-5 inhibitors for erectile dysfunction (ED): Refer to the prescribing information of PDE-5 inhibitors for dose recommendations. Sedatives/Hypnotics: midazolam (oral) triazolam ↑ midazolam (oral) ↑ triazolam Use with caution when midazolam or triazolam is concomitantly administered with SUNLENCA 7.4 Drugs without Clinically Significant Interactions with SUNLENCA Based on drug interaction studies conducted with SUNLENCA, no clinically significant drug interactions have been observed with: darunavir/cobicistat, cobicistat, famotidine, pitavastatin, rosuvastatin, tenofovir alafenamide, and voriconazole.

Store bottle and blister packs at 20 °C – 25 °C (68 °F – 77 °F), excursions permitted to 15 °C – 30 °C (59 °F – 86 °F) (see USP Controlled Room Temperature). Dispense and store only in original bottle or blister pack. Store at 20 °C – 25 °C (68 °F – 77 °F), excursions permitted to 15 °C – 30 °C (59 °F – 86 °F). Keep the vials in the original carton until just prior to preparation of the injections in order to protect from light. Once the solution has been drawn into the syringes, the injections should be administered as soon as possible. Discard any unused portion of the solution.