Sunlenca® (lenacapavir)

Administration Outside the Dosing Window

This document is in response to your request for information regarding Sunlenca® (lenacapavir [LEN]) and administration outside the dosing window.

Gilead Sciences is unable to provide treatment recommendations. We recommend that you use your best clinical judgment in guiding therapy based on patient-specific therapeutic goals.

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

The full indication, important safety information, and boxed warnings are available at:
www.gilead.com/-/media/files/pdfs/medicines/hiv/sunlenca/sunlenca_pi.

Product Labeling1

Adherence to Treatment Regimen

Prior to starting LEN, 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 LEN 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.

Recommended Dosage

LEN can be initiated using one of the two recommended dosage regimens (Table 1 and Table 2). 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. LEN oral tablets may be taken with or without food.

Table 1. Recommended Treatment Regimen for LEN Initiation and Maintenance,
Option 11

aFrom the date of the last injection.

Table 2. Recommended Treatment Regimen for LEN Initiation and Maintenance,
Option 21

aFrom the date of the last injection.

Recommended Dosing Schedule for Missed Dose1

Planned Missed Injections

During the maintenance period, if a patient plans to miss a scheduled 6-month injection visit by more than 2 weeks, LEN tablets may be taken for up to 6 months until injections resume (Table 3).

Table 3. Recommended Dosage after Planned Missed Injections:
Weekly Oral Maintenance1

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 LEN 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.

Table 4. Recommended Dosage after Unplanned Missed Injections1

Oral Bridging With Once Weekly LEN 300 mg

Study design and demographics

A post hoc analysis was conducted to assess the efficacy and safety of oral bridging with LEN 300 mg once weekly among participants enrolled in the CAPELLA (highly treatment‑experienced PWH with multidrug resistance) and CALIBRATE (ARV‑naïve PWH) studies whose LEN SUBQ dosing was interrupted from December 2021 to May 2022.2 PK model simulations were used to predict that an oral LEN 300-mg once‑weekly dosing schedule would maintain the lower bounds of the 90% CI for the mean trough concentrations above the IQ4 of 15.5 ng/mL during the oral bridging period.3 Oral bridging was initiated within 2 weeks of the next scheduled SUBQ injection, and participants were given oral LEN to administer at home. See Figure 1 and Figure 2 for the modified CAPELLA and CALIBRATE study designs.2

Figure 1. CAPELLA: Study Design2,4,5

Abbreviations: HTE=highly treatment-experienced; INSTI=integrase strand transfer inhibitor; NNRTI=non-nucleos(t)ide reverse transcriptase inhibitor; NRTI=nucleos(t)ide reverse transcriptase inhibitor; PBO=placebo; PI=protease inhibitor.

aParticipants with <0.5 log10 decline in HIV-1 RNA and HIV-1 RNA ≥400 c/mL were enrolled in the randomized cohort; participants were enrolled in the nonrandomized cohort if they had ≥0.5 log10 decline in HIV-1 RNA and/or had HIV-1 RNA <400 c/mL or were enrolled after the randomized cohort was fully recruited.

bOral LEN dosing schedule: Day 1, 600 mg; Day 2, 600 mg; and Day 8, 300 mg.

cSUBQ LEN dosing schedule: 927 mg (2× 1.5 mL) on Day 15 and then every 6 months.

Note: ATV, ATV/cobicistat, ATV/ritonavir, efavirenz, etravirine, nevirapine, and tipranavir were not permitted for use in the OBR.

Figure 2. CALIBRATE: Study Design2,6

aThe LEN dosing schedule included an oral lead-in phase (Day 1, 600 mg; Day 2, 600 mg; Day 8, 300 mg), followed by SUBQ LEN 927 mg (2 × 1.5 mL) on Day 15 and every 6 months (26 weeks) thereafter.

bParticipants needed to have HIV-1 RNA <50 c/mL at Weeks 16 and 22 to initiate treatment with a two‑agent regimen at Week 28. Those with HIV-1 RNA ≥50 c/mL discontinued the study at Week 28.

cThe oral LEN dosing schedule consisted of the following: 600 mg on Day 1, 600 mg on Day 2, and 50 mg on Day 3 and thereafter.

Note: The following doses were used: FTC/TAF, 200/25 mg; TAF, 25 mg; BIC, 75 mg; and BIC/FTC/TAF, 50/200/25 mg.

Baseline demographics and characteristics for the participants who received oral bridging in either study are presented in Table 5.

Table 5. CAPELLA (Combined Cohorts) and CALIBRATE: Baseline Demographics and Characteristics: Oral Bridging Analysis Set2a

aComprised all participants with ≥1 dose of LEN 300 mg oral bridging.

Efficacy2

In the CAPELLA and CALIBRATE studies, the median duration of LEN oral bridging was 18 weeks; the mean (SD) exposure to oral LEN was 17.8 (7.66) weeks in CAPELLA, 18.1 (5.27) weeks in CALIBRATE Group 1, and 18.2 (5.18) weeks in CALIBRATE Group 2. The mean adherence to oral LEN per pill count was 96.9% in CAPELLA, 94.8% in CALIBRATE Group 1, and 96.7% in CALIBRATE Group 2. Among participants who were virologically suppressed when oral bridging began, CD4 counts remained stable throughout the oral bridging period. Of the 11 participants who were viremic at the oral bridging baseline, 27% (3/11) of participants achieved virologic suppression at Week 10, and 50% (2/4) of participants achieved virologic suppression at Week 20. Efficacy of LEN 300 mg during oral bridging among participants who were virologically suppressed when oral bridging began is presented in Figure 3.

Figure 3. CAPELLA (Combined Cohorts) and CALIBRATE:
Efficacy During Oral Bridging (Missing=Excluded Analysis)2

aOne participant did not maintain HIV-1 RNA <50 c/mL during the oral bridging period at Week 10 and 20; the participant developed a LEN resistance-associated mutation (ie, N74D) and had missed two nonconsecutive oral doses prior to developing elevated HIV-1 RNA levels. After the oral bridging period, the participant achieved virologic suppression without changing regimens.

PK data3

PK samples were collected from participants in both studies at the beginning of the oral bridging period and every 10 to 12 weeks thereafter until SUBQ LEN was resumed. In both studies, the mean LEN plasma concentrations and lower bounds of the 90% CI were above IQ4 (15.5 ng/mL) at Day 1, Weeks 10, 20, and 30, and at the SUBQ LEN resumption visit.

Safety2

Oral LEN 300-mg bridging was generally well tolerated across both studies and had a safety profile consistent with SUBQ LEN in the primary analysis, aside from injection site reactions (Table 6). No serious or Grade ≥3 TEAEs were deemed to be related to LEN, and no TEAE led to study discontinuation. One participant in the CAPELLA study with a history of alcoholic hepatitis died of an unknown cause during the oral bridging period; the death was not considered by the investigator to be related to LEN treatment.

Table 6. CAPELLA and CALIBRATE: Safety Summary (Oral Bridging Analysis Set)2

aCAPELLA, COVID-19 (7%); CALIBRATE, influenza (8.5%), COVID-19 (4.9%).

Simulations for Missed Oral LEN Loading Doses7

Study design

A two-compartment population-PK model was used to simulate plasma LEN concentration‑time profiles for various missed-dose scenarios of the Day 2 and Day 8 oral loading doses of the CAPELLA phase 2/3 regimen. These scenarios were evaluated at the start and restart of treatment (when a SUBQ LEN dose was missed by >2 weeks, treatment was restarted on Day 1 of the regimen). Simulated scenarios consisted of the following: missed Day 2 oral dose by <6 days or ≥6 days and missed Day 8 oral dose by <6 days or ≥6 days.

Results

Based on simulated scenarios, therapeutic LEN plasma concentrations were maintained by the following actions after a missed dose for either the start or restart of treatment (Table 7).

Table 7. Summary of Missed LEN Oral Loading Doses Scenarios in Phase 2/3 Regimen for the Start and Restart of Treatment7

aTherapeutic LEN plasma concentrations=mean (90% CI) LEN plasma concentrations (ng/mL).

bCurrent data indicate maximal antiviral activity was achieved at a mean trough concentration of 15.5 ng/mL.

Early Dosing

A literature search was conducted in Ovid MEDLINE, BIOSIS Previews, and Embase databases for studies published between 1946 and August 13, 2024, using the search terms of Sunlenca, lenacapavir, early dosing, and other related search terms. No relevant citations were identified.

References

1. SUNLENCA, Gilead Sciences Inc. SUNLENCA® (lenacapavir) tablets, for oral use. SUNLENCA® (lenacapavir) injection, for subcutaneous use. US Prescribing Information. Foster City, CA.
2. Ogbuagu O, Avihingsanon A, Segal-Maurer S, et al. Lenacapavir Oral Bridging (300 mg QW) Maintains Efficacy with a Similar Safety Profile When SC LEN Cannot Be Administered. [Abstract Oral OAB0205]. Paper presented at: 12th IAS Conference on HIV Science; July 23-26, 2023; Brisbane, Australia.
3. Jogiraju V, Shelton M, Shaik N, et al. Pharmacokinetic Bridging with Oral Lenacapavir for Missed Subcutaneous Q6M Dosing. [Poster TUPEB07]. Paper presented at: 12th IAS Conference on HIV Science; July 23-26, 2023; Brisbane, Australia.
4. Ogbuagu O, Segal-Maurer S, Brinson C, et al. Long-Acting Lenacapavir in People With Multidrug-Resistant HIV-1: Week 52 Results [Poster 1047]. Paper presented at: Virtual Conference on Retroviruses and Opportunistic Infections (CROI) 2022; 12-16 February, 2022.
5. Gilead Sciences Inc. Data on File.
6. Gupta SK, Sims J, Brinson C, et al. Lenacapavir as part of a Combination Regimen in Treatment-Naïve People with HIV: Week 54 Results [Presentation]. Paper presented at: Virtual Conference on Retroviruses and Opportunistic Infections (CROI) 2022; 12-16 February, 2022.
7. Singh R, Shaik NA, Bellanti F, et al. Recommendations for Missed Oral Lenacapavir Loading Doses Using Population Pharmacokinetics Based Simulations. [Poster TUPEB14]. Paper presented at: 12th IAS Conference on HIV Science; July 23-26, 2023; Brisbane, Australia.

Abbreviations

ARV=antiretroviral
ATV=atazanavir
BIC=bictegravir
c/mL=copies/mL
CD4=cluster of differentiation 4
FTC=emtricitabine
IQ4=inhibitory quotient 4
LEN=lenacapavir
OBR=optimized background regimen
PK=pharmacokinetic

PWH=people with HIV
SUBQ=subcutaneous(ly)
TAF=tenofovir alafenamide
TEAE=treatment emergent adverse events
 

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Sunlenca US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/hiv/sunlenca/sunlenca_pi.

Follow-Up

For any additional questions, please contact Gilead Medical Information at:

☎1‐866‐MEDI‐GSI (1‐866‐633‐4474) or   www.askgileadmedical.com

Adverse Event Reporting

Please report all adverse events to:

Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
 www.gilead.com/utility/contact/report-an-adverse-event

FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or   www.accessdata.fda.gov/scripts/medwatch

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