These Highlights Do Not Include All The Information Needed To Use Sunlenca Safely And Effectively. See Full Prescribing Information For Sunlenca.

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.

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.

No data are available on overdose of SUNLENCA in patients. If overdose occurs, monitor the patient for evidence of toxicity. Treatment of overdose with SUNLENCA consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. As lenacapavir is highly bound to plasma proteins, it is unlikely to be significantly removed by dialysis.

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-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-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)-1H-indazol-3-yl)(methylsulfonyl)amide.

Lenacapavir sodium has a molecular formula of C₃₉H₃₁ClF₁₀N₇NaO₅S_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.

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

Clinical studies of SUNLENCA did not include sufficient numbers of participants aged 65 and over to determine whether they respond differently from younger patients.

The efficacy and safety of SUNLENCA in heavily treatment-experienced participants with multidrug resistant HIV-1 is based on 52-week data from CAPELLA, a randomized, placebo-controlled, double-blind, multicenter trial (NCT 04150068).

CAPELLA was conducted in 72 heavily treatment-experienced participants with multiclass resistant HIV-1. Participants were required to have a viral load ≥ 400 copies/mL, documented resistance to at least two antiretroviral medications from each of at least 3 of the 4 classes of antiretroviral medications (NRTI, NNRTI, PI and INSTI), and ≤ 2 fully active antiretroviral medications from the 4 classes of antiretroviral medications remaining at baseline due to resistance, intolerability, drug access, contraindication, or other safety concerns.

The trial was composed of two cohorts. Participants were enrolled into the randomized cohort (cohort 1, N=36) if they had a < 0.5 log₁₀ HIV-1 RNA decline compared to the screening visit. Participants were enrolled into the non-randomized cohort (cohort 2, N=36) if they had a ≥ 0.5 log₁₀ HIV-1 RNA decline compared to the screening visit or after cohort 1 reached its planned sample size.

In the 14-day functional monotherapy period, participants in cohort 1 were randomized in a 2:1 ratio in a blinded fashion to receive either SUNLENCA or placebo, while continuing their failing regimen. This period was to establish the virologic activity of SUNLENCA. After the functional monotherapy period, participants who had received SUNLENCA continued on SUNLENCA along with an optimized background regimen (OBR); participants who had received placebo during this period initiated SUNLENCA along with an OBR.

Participants in cohort 1 had a mean age of 52 years (range: 24 to 71), 72% were male, 46% were White, 46% were Black, and 9% were Asian. 29% percent of participants identified as Hispanic/Latino. The mean baseline plasma HIV-1 RNA was 4.3 log₁₀ copies/mL (range: 2.3 to 5.4). 19% of participants had baseline viral loads greater than 100,000 copies/mL. The mean baseline CD4⁺ cell count was 161 cells/mm³ (range: 6 to 827). 75% of participants had CD4⁺ cell counts below 200 cells/mm³. The mean number of years since participants first started HIV treatment was 24 years (range: 7 to 33); the mean number of antiretroviral agents in failing regimens at baseline was 4 (range: 1 to 7). The percentage of participants in the randomized cohort with known resistance to at least 2 agents from the NRTI, NNRTI, PI and INSTI classes was 97%, 94%, 78% and 75%, respectively. In cohort 1, 53% of participants had no fully active agents, 31% had 1 fully active agent, and 17% had 2 or more fully active agents within their initial failing regimen, including 6% of participants were who were receiving fostemsavir, which was an investigational agent at the start of the CAPELLA trial.

Participants in cohort 2 initiated SUNLENCA and an OBR on Day 1.

Participants in cohort 2 had a mean age of 48 years (range: 23 to 78), 78% were male, 36% were White, 31% were Black, 33% were Asian, and 14% of participants identified as Hispanic/Latino. The mean baseline plasma HIV-1 RNA was 4.1 log₁₀ copies/mL (range: 1.3 to 5.7). 19% of participants had baseline viral loads greater than 100,000 copies/mL. The mean baseline CD4⁺ cell count was 258 cells/mm³ (range: 3 to 1296). 53% of participants had CD4⁺ cell counts below 200 cells/mm³. The mean number of years since participants first started HIV treatment was 19 years (range: 3 to 35); the mean number of antiretroviral agents in failing regimens at baseline was 4 (range: 2 to 7). The percentage of participants in the non-randomized cohort with known resistance to at least 2 agents from the NRTI, NNRTI, PI and INSTI classes was 100%, 100%, 83% and 64%, respectively. In cohort 2, 31% of participants had no fully active agents, 42% had 1 fully active agent, and 28% had 2 or more fully active agents within their initial failing regimen, including 6% of participants who were receiving fostemsavir, which was an investigational agent at the start of the CAPELLA trial.

The primary efficacy endpoint was the proportion of participants in cohort 1 achieving ≥ 0.5 log₁₀ copies/mL reduction from baseline in HIV-1 RNA at the end of the functional monotherapy period. The results of the primary endpoint analysis are shown in Table 10.

The results at Weeks 26 and 52 are provided in Table 11 and Table 12.

In cohort 1, at Weeks 26 and 52, the mean change from baseline in CD4⁺ cell count was 81 cells/mm³ (range: -101 to 522) and 82 cells/mm³ (range: -194 to 467), respectively.

In cohort 2, at Weeks 26 and 52, 81% (29/36) and 72% (26/36) of participants achieved HIV-1 RNA < 50 copies/mL, respectively, and the mean change from baseline in CD4⁺ cell count was 97 cells/mm³ (range: -103 to 459) and 113 cells/mm³ (range: -124 to 405), respectively.

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)].

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)].

• Consult the Full Prescribing Information prior to and during treatment for important drug interactions. (4, 7, 12.3)

No dosage adjustment of SUNLENCA is recommended in patients with mild, moderate or severe renal impairment (estimated creatinine clearance greater than or equal to 15 mL per minute). SUNLENCA has not been studied in patients with ESRD (estimated creatinine clearance less than 15 mL per minute) [see Clinical Pharmacology (12.3)].

The pharmacokinetic (PK) properties of lenacapavir are provided in Table 6 and Table 7. The estimated lenacapavir exposures are comparable between the two recommended dosing regimens.

Lenacapavir exposures after subcutaneous administration were similar between heavily treatment experienced participants with HIV-1 and participants without HIV-1 based on population pharmacokinetics analysis. Lenacapavir exposures (AUC_tau, C_max and C_trough) after oral administration were 28% to 43% higher in participants with HIV-1 who were heavily treatment experienced, compared to participants without HIV-1 based on population PK analysis. These differences were not considered clinically relevant.

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)].

No dosage adjustment of SUNLENCA is recommended in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. SUNLENCA has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) [see Clinical Pharmacology (12.3)].

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 is an HIV-1 antiretroviral agent [see Microbiology (12.4)].

• Immune reconstitution syndrome: May necessitate further evaluation and treatment. (5.1)
• Residual concentrations of lenacapavir may remain in systemic circulation for up to 12 months or longer. Counsel patients regarding the dosing schedule; non-adherence could lead to loss of virologic response and development of resistance. (5.2)
• May increase exposure and risk of adverse reactions to drugs primarily metabolized by CYP3A initiated within 9 months after the last subcutaneous dose of SUNLENCA. (5.2)
• If discontinued, initiate an alternative, fully suppressive antiretroviral regimen where possible no later than 28 weeks after the final injection of SUNLENCA. If virologic failure occurs, switch to an alternative regimen if possible. (5.2)
• Injection site reactions may occur, and nodules and indurations may be persistent. Improper administration (intradermal injection) has been associated with serious injection site reactions. (5.3)

• 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)

• 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)

Tablets: 300 mg

Injection: 463.5 mg/1.5 mL (309 mg/mL) in single-dose vials. (3)

Administration of SUNLENCA may result in local injection site reactions (ISRs). If clinically significant ISRs occur, evaluate and institute appropriate therapy and follow-up.

Manifestations of ISRs may include swelling, pain, erythema, nodule, induration, pruritus, extravasation or mass. Nodules and indurations at the injection site may take longer to resolve than other ISRs. In clinical studies, 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. Measurements and qualitative assessments of ISRs were not routinely reported. Where described, the majority of the injection site nodules and indurations were palpable but not visible, and had a maximum size of approximately 1 to 4 cm [see Adverse Reactions (6.1)].

The mechanism driving the persistence of injection site nodules and indurations in some patients is not fully understood, but based on available data, they may be related to the presence of the subcutaneous drug depot. In some patients who had a skin biopsy performed of an injection site nodule or induration, dermatopathology revealed foreign body inflammation or granulomatous response.

Improper administration (intradermal injection) has been associated with serious injection site reactions, including necrosis and ulcer [see Adverse Reactions (6)]. Ensure SUNLENCA is only administered subcutaneously in the abdomen [see Dosage and Administration (2.4)].

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.

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.

The majority (96%) of all adverse reactions associated with SUNLENCA were mild or moderate in severity.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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)].

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves' disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

R_x only

NDC 61958-3002-1

Sunlenca^®

(lenacapavir) injection

463.5 mg/1.5 mL (309 mg/mL)

For Subcutaneous Injection

Contents

• 2 x 1.5 mL lenacapavir single-dose vials
• 2 vial access devices
• 2 syringes
• 2 injection needles (22 gauge, 1/2 inch)
• Prescribing Information
• Instructions for Use
• Patient Information

Both 463.5 mg/1.5 mL (2 single-dose vials) must be

administered to receive the 927 mg dose.

For Healthcare Professional administration only.

GILEAD

Lenacapavir is a substrate of P-gp, UGT1A1, and CYP3A.

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.

R_x only

NDC 61958-3005-1

Sunlenca^®

(lenacapavir) injection

463.5 mg/1.5 mL (309 mg/mL)

For Subcutaneous Injection

Contents

• 2 x 1.5 mL lenacapavir single-dose vials
• 2 withdrawal needles (18 gauge, 1½ inch)
• 2 syringes
• 2 injection needles (22 gauge, ½ inch)
• Prescribing Information
• Instructions for Use
• Patient Information

Both 463.5 mg/1.5 mL (2 single-dose vials) must be

administered to receive the 927 mg dose.

For Healthcare Professional administration only.

GILEAD

NDC 61958-3001-3

4 tablets

Sunlenca^®

(lenacapavir) tablets

300 mg per tablet

Talk to your healthcare provider

before taking Sunlenca tablets.

Your healthcare provider will tell you

when to take Sunlenca tablets.

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.

NDC 61958-3001-2

Sunlenca^®

(lenacapavir) tablets

300 mg per tablet

1 pouch containing 5 tablets

Each tablet contains: 300 mg of lenacapavir

(present as 306.8 mg lenacapavir sodium).

Store at 20 °C - 25 °C (68 °F - 77 °F).

Dispense only in original container.

Recommended Dosage: See prescribing information.

KEEP OUT OF THE REACH OF CHILDREN

Talk to your healthcare provider before taking

Sunlenca tablets.

Your healthcare provider will tell you when to take

Sunlenca tablets.

GILEAD

Manufactured for:

Gilead Sciences, Inc.

Foster City, CA 94404

Made in Canada

© 2022 Gilead Sciences, Inc.

NDC 61958-3001-1

Sunlenca^®

(lenacapavir) tablets

300 mg per tablet

1 pouch containing 4 tablets

Each tablet contains: 300 mg of lenacapavir

(present as 306.8 mg lenacapavir sodium).

Store at 20 °C - 25 °C (68 °F - 77 °F).

Dispense only in original container.

Recommended Dosage: See prescribing information.

KEEP OUT OF THE REACH OF CHILDREN

GILEAD

Manufactured for:

Gilead Sciences, Inc.

Foster City, CA 94404

Made in Canada

© 2022 Gilead Sciences, Inc.

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)].

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.

Residual concentrations of lenacapavir may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer after the last subcutaneous dose). It is important to counsel patients that maintenance dosing by injection is required every 6 months, because missed doses or non-adherence to injections could lead to loss of virologic response and development of resistance [see Dosage and Administration (2.1)].

Lenacapavir, a moderate CYP3A inhibitor, may increase the exposure to, and therefore potential risk of adverse reactions from, drugs primarily metabolized by CYP3A initiated within 9 months after the last subcutaneous dose of SUNLENCA [see Drug Interactions and Clinical Pharmacology (7.2, 12.3)].

If SUNLENCA is discontinued, to minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen where possible no later than 28 weeks after the final injection of SUNLENCA. If virologic failure occurs during treatment, switch the patient to an alternative regimen if possible [see Dosage and Administration (2.1)].

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.

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.

No data are available on overdose of SUNLENCA in patients. If overdose occurs, monitor the patient for evidence of toxicity. Treatment of overdose with SUNLENCA consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. As lenacapavir is highly bound to plasma proteins, it is unlikely to be significantly removed by dialysis.

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-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-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)-1H-indazol-3-yl)(methylsulfonyl)amide.

Lenacapavir sodium has a molecular formula of C₃₉H₃₁ClF₁₀N₇NaO₅S_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.

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

Clinical studies of SUNLENCA did not include sufficient numbers of participants aged 65 and over to determine whether they respond differently from younger patients.

The efficacy and safety of SUNLENCA in heavily treatment-experienced participants with multidrug resistant HIV-1 is based on 52-week data from CAPELLA, a randomized, placebo-controlled, double-blind, multicenter trial (NCT 04150068).

CAPELLA was conducted in 72 heavily treatment-experienced participants with multiclass resistant HIV-1. Participants were required to have a viral load ≥ 400 copies/mL, documented resistance to at least two antiretroviral medications from each of at least 3 of the 4 classes of antiretroviral medications (NRTI, NNRTI, PI and INSTI), and ≤ 2 fully active antiretroviral medications from the 4 classes of antiretroviral medications remaining at baseline due to resistance, intolerability, drug access, contraindication, or other safety concerns.

The trial was composed of two cohorts. Participants were enrolled into the randomized cohort (cohort 1, N=36) if they had a < 0.5 log₁₀ HIV-1 RNA decline compared to the screening visit. Participants were enrolled into the non-randomized cohort (cohort 2, N=36) if they had a ≥ 0.5 log₁₀ HIV-1 RNA decline compared to the screening visit or after cohort 1 reached its planned sample size.

In the 14-day functional monotherapy period, participants in cohort 1 were randomized in a 2:1 ratio in a blinded fashion to receive either SUNLENCA or placebo, while continuing their failing regimen. This period was to establish the virologic activity of SUNLENCA. After the functional monotherapy period, participants who had received SUNLENCA continued on SUNLENCA along with an optimized background regimen (OBR); participants who had received placebo during this period initiated SUNLENCA along with an OBR.

Participants in cohort 1 had a mean age of 52 years (range: 24 to 71), 72% were male, 46% were White, 46% were Black, and 9% were Asian. 29% percent of participants identified as Hispanic/Latino. The mean baseline plasma HIV-1 RNA was 4.3 log₁₀ copies/mL (range: 2.3 to 5.4). 19% of participants had baseline viral loads greater than 100,000 copies/mL. The mean baseline CD4⁺ cell count was 161 cells/mm³ (range: 6 to 827). 75% of participants had CD4⁺ cell counts below 200 cells/mm³. The mean number of years since participants first started HIV treatment was 24 years (range: 7 to 33); the mean number of antiretroviral agents in failing regimens at baseline was 4 (range: 1 to 7). The percentage of participants in the randomized cohort with known resistance to at least 2 agents from the NRTI, NNRTI, PI and INSTI classes was 97%, 94%, 78% and 75%, respectively. In cohort 1, 53% of participants had no fully active agents, 31% had 1 fully active agent, and 17% had 2 or more fully active agents within their initial failing regimen, including 6% of participants were who were receiving fostemsavir, which was an investigational agent at the start of the CAPELLA trial.

Participants in cohort 2 initiated SUNLENCA and an OBR on Day 1.

Participants in cohort 2 had a mean age of 48 years (range: 23 to 78), 78% were male, 36% were White, 31% were Black, 33% were Asian, and 14% of participants identified as Hispanic/Latino. The mean baseline plasma HIV-1 RNA was 4.1 log₁₀ copies/mL (range: 1.3 to 5.7). 19% of participants had baseline viral loads greater than 100,000 copies/mL. The mean baseline CD4⁺ cell count was 258 cells/mm³ (range: 3 to 1296). 53% of participants had CD4⁺ cell counts below 200 cells/mm³. The mean number of years since participants first started HIV treatment was 19 years (range: 3 to 35); the mean number of antiretroviral agents in failing regimens at baseline was 4 (range: 2 to 7). The percentage of participants in the non-randomized cohort with known resistance to at least 2 agents from the NRTI, NNRTI, PI and INSTI classes was 100%, 100%, 83% and 64%, respectively. In cohort 2, 31% of participants had no fully active agents, 42% had 1 fully active agent, and 28% had 2 or more fully active agents within their initial failing regimen, including 6% of participants who were receiving fostemsavir, which was an investigational agent at the start of the CAPELLA trial.

The primary efficacy endpoint was the proportion of participants in cohort 1 achieving ≥ 0.5 log₁₀ copies/mL reduction from baseline in HIV-1 RNA at the end of the functional monotherapy period. The results of the primary endpoint analysis are shown in Table 10.

The results at Weeks 26 and 52 are provided in Table 11 and Table 12.

In cohort 1, at Weeks 26 and 52, the mean change from baseline in CD4⁺ cell count was 81 cells/mm³ (range: -101 to 522) and 82 cells/mm³ (range: -194 to 467), respectively.

In cohort 2, at Weeks 26 and 52, 81% (29/36) and 72% (26/36) of participants achieved HIV-1 RNA < 50 copies/mL, respectively, and the mean change from baseline in CD4⁺ cell count was 97 cells/mm³ (range: -103 to 459) and 113 cells/mm³ (range: -124 to 405), respectively.

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)].

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)].

• Consult the Full Prescribing Information prior to and during treatment for important drug interactions. (4, 7, 12.3)

No dosage adjustment of SUNLENCA is recommended in patients with mild, moderate or severe renal impairment (estimated creatinine clearance greater than or equal to 15 mL per minute). SUNLENCA has not been studied in patients with ESRD (estimated creatinine clearance less than 15 mL per minute) [see Clinical Pharmacology (12.3)].

The pharmacokinetic (PK) properties of lenacapavir are provided in Table 6 and Table 7. The estimated lenacapavir exposures are comparable between the two recommended dosing regimens.

Lenacapavir exposures after subcutaneous administration were similar between heavily treatment experienced participants with HIV-1 and participants without HIV-1 based on population pharmacokinetics analysis. Lenacapavir exposures (AUC_tau, C_max and C_trough) after oral administration were 28% to 43% higher in participants with HIV-1 who were heavily treatment experienced, compared to participants without HIV-1 based on population PK analysis. These differences were not considered clinically relevant.

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)].

No dosage adjustment of SUNLENCA is recommended in patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. SUNLENCA has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) [see Clinical Pharmacology (12.3)].

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 is an HIV-1 antiretroviral agent [see Microbiology (12.4)].

• Immune reconstitution syndrome: May necessitate further evaluation and treatment. (5.1)
• Residual concentrations of lenacapavir may remain in systemic circulation for up to 12 months or longer. Counsel patients regarding the dosing schedule; non-adherence could lead to loss of virologic response and development of resistance. (5.2)
• May increase exposure and risk of adverse reactions to drugs primarily metabolized by CYP3A initiated within 9 months after the last subcutaneous dose of SUNLENCA. (5.2)
• If discontinued, initiate an alternative, fully suppressive antiretroviral regimen where possible no later than 28 weeks after the final injection of SUNLENCA. If virologic failure occurs, switch to an alternative regimen if possible. (5.2)
• Injection site reactions may occur, and nodules and indurations may be persistent. Improper administration (intradermal injection) has been associated with serious injection site reactions. (5.3)

• 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)

• 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)

Tablets: 300 mg

Injection: 463.5 mg/1.5 mL (309 mg/mL) in single-dose vials. (3)

Administration of SUNLENCA may result in local injection site reactions (ISRs). If clinically significant ISRs occur, evaluate and institute appropriate therapy and follow-up.

Manifestations of ISRs may include swelling, pain, erythema, nodule, induration, pruritus, extravasation or mass. Nodules and indurations at the injection site may take longer to resolve than other ISRs. In clinical studies, 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. Measurements and qualitative assessments of ISRs were not routinely reported. Where described, the majority of the injection site nodules and indurations were palpable but not visible, and had a maximum size of approximately 1 to 4 cm [see Adverse Reactions (6.1)].

The mechanism driving the persistence of injection site nodules and indurations in some patients is not fully understood, but based on available data, they may be related to the presence of the subcutaneous drug depot. In some patients who had a skin biopsy performed of an injection site nodule or induration, dermatopathology revealed foreign body inflammation or granulomatous response.

Improper administration (intradermal injection) has been associated with serious injection site reactions, including necrosis and ulcer [see Adverse Reactions (6)]. Ensure SUNLENCA is only administered subcutaneously in the abdomen [see Dosage and Administration (2.4)].

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.

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.

The majority (96%) of all adverse reactions associated with SUNLENCA were mild or moderate in severity.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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)].

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves' disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

R_x only

NDC 61958-3002-1

Sunlenca^®

(lenacapavir) injection

463.5 mg/1.5 mL (309 mg/mL)

For Subcutaneous Injection

Contents

• 2 x 1.5 mL lenacapavir single-dose vials
• 2 vial access devices
• 2 syringes
• 2 injection needles (22 gauge, 1/2 inch)
• Prescribing Information
• Instructions for Use
• Patient Information

Both 463.5 mg/1.5 mL (2 single-dose vials) must be

administered to receive the 927 mg dose.

For Healthcare Professional administration only.

GILEAD

Lenacapavir is a substrate of P-gp, UGT1A1, and CYP3A.

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.

R_x only

NDC 61958-3005-1

Sunlenca^®

(lenacapavir) injection

463.5 mg/1.5 mL (309 mg/mL)

For Subcutaneous Injection

Contents

• 2 x 1.5 mL lenacapavir single-dose vials
• 2 withdrawal needles (18 gauge, 1½ inch)
• 2 syringes
• 2 injection needles (22 gauge, ½ inch)
• Prescribing Information
• Instructions for Use
• Patient Information

Both 463.5 mg/1.5 mL (2 single-dose vials) must be

administered to receive the 927 mg dose.

For Healthcare Professional administration only.

GILEAD

NDC 61958-3001-3

4 tablets

Sunlenca^®

(lenacapavir) tablets

300 mg per tablet

Talk to your healthcare provider

before taking Sunlenca tablets.

Your healthcare provider will tell you

when to take Sunlenca tablets.

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.

NDC 61958-3001-2

Sunlenca^®

(lenacapavir) tablets

300 mg per tablet

1 pouch containing 5 tablets

Each tablet contains: 300 mg of lenacapavir

(present as 306.8 mg lenacapavir sodium).

Store at 20 °C - 25 °C (68 °F - 77 °F).

Dispense only in original container.

Recommended Dosage: See prescribing information.

KEEP OUT OF THE REACH OF CHILDREN

Talk to your healthcare provider before taking

Sunlenca tablets.

Your healthcare provider will tell you when to take

Sunlenca tablets.

GILEAD

Manufactured for:

Gilead Sciences, Inc.

Foster City, CA 94404

Made in Canada

© 2022 Gilead Sciences, Inc.

NDC 61958-3001-1

Sunlenca^®

(lenacapavir) tablets

300 mg per tablet

1 pouch containing 4 tablets

Each tablet contains: 300 mg of lenacapavir

(present as 306.8 mg lenacapavir sodium).

Store at 20 °C - 25 °C (68 °F - 77 °F).

Dispense only in original container.

Recommended Dosage: See prescribing information.

KEEP OUT OF THE REACH OF CHILDREN

GILEAD

Manufactured for:

Gilead Sciences, Inc.

Foster City, CA 94404

Made in Canada

© 2022 Gilead Sciences, Inc.

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)].

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.

Residual concentrations of lenacapavir may remain in the systemic circulation of patients for prolonged periods (up to 12 months or longer after the last subcutaneous dose). It is important to counsel patients that maintenance dosing by injection is required every 6 months, because missed doses or non-adherence to injections could lead to loss of virologic response and development of resistance [see Dosage and Administration (2.1)].

Lenacapavir, a moderate CYP3A inhibitor, may increase the exposure to, and therefore potential risk of adverse reactions from, drugs primarily metabolized by CYP3A initiated within 9 months after the last subcutaneous dose of SUNLENCA [see Drug Interactions and Clinical Pharmacology (7.2, 12.3)].

If SUNLENCA is discontinued, to minimize the potential risk of developing viral resistance, it is essential to initiate an alternative, fully suppressive antiretroviral regimen where possible no later than 28 weeks after the final injection of SUNLENCA. If virologic failure occurs during treatment, switch the patient to an alternative regimen if possible [see Dosage and Administration (2.1)].