Sunlenca® (lenacapavir)

Oral Initiation Dosing

This document is in response to your request for information regarding the use of Sunlenca® (lenacapavir [LEN]) and oral initiation dosing.

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: http://www.gilead.com/-/media/files/pdfs/medicines/hiv/sunlenca/sunlenca_pi.

Summary

Product Labeling1

LEN can be initiated using one of the two recommended dosage regimens. 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.

• Initiation Option 1: Day 1: 927 mg SUBQ (2 × 1.5 mL injections) and 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 SUBQ (2 × 1.5 mL injections).
• Maintenance: 927 mg SUBQ (2 × 1.5 mL injections) every 6 months (26 weeks) from the date of the last injection ±2 weeks.

Clinical Data on Oral Initiation Dosing of LEN

Due to the slow initial release of SUBQ LEN, an oral initiation regimen is necessary for PK purposes. PK simulations were conducted to support the use of LEN with an oral initiation regimen followed by SUBQ maintenance every 6 months.2

• The combination of oral LEN initiation doses followed by a single SUBQ injection was predicted to achieve the LEN target concentration of 24 ng/mL within a few days after administration; the target concentration was expected to be maintained through 26 weeks (6 months).

A phase 1 study in healthy volunteers compared the PK and evaluated the safety and tolerability of a phase 2/3 regimen, which included individual doses of oral LEN and SUBQ LEN, and a simplified regimen, which included concurrent dosing of oral LEN and SUBQ LEN.3

• For both regimens, mean LEN concentrations reached the efficacious target (IQ4 of 15.5 ng/mL) rapidly and were maintained throughout the dosing interval of 6 months.
• LEN concentrations in the simplified regimen were generally comparable to those in the phase 2/3 regimen.
• Both regimens were well tolerated, and there were no Grade 3, Grade 4, or serious AEs. No deaths were reported.

Clinical Data on Oral Initiation Dosing of LEN

LEN Dosing Regimen Simulations in Ongoing Phase 2/3 Studies2,4

The formulation of LEN 309 mg/mL SUBQ injection has a slow initial drug release that requires an oral initiation dose prior to administration of the first injection. In a phase 1 study, LEN plasma concentrations were ≥24 ng/mL (mean IQ ≥6 ng/mL) for 26 weeks after administration of a single LEN 927 mg SUBQ injection (Figure 1). The time to maximum concentration of LEN ranged from 11 to 14 weeks after dose administration, and the half-life ranged from 7 to 11 weeks. PK simulations were conducted using PK results for the SUBQ injection from this phase 1 study and PK results for the oral LEN tablet from a separate study. The combination of oral LEN initiation doses followed by a single SUBQ injection was predicted to achieve the LEN target concentration of 24 ng/mL within a few days after administration; the target concentration was expected to be maintained through 26 weeks (6 months; Figure 2).

Figure 1. LEN Plasma Concentration-Time Profiles (Begley et al)2,4

aThe IQ is the ratio of LEN plasma concentration to the effective concentration to cause inhibition by 95%. bDose originally presented as 300 mg and 900 mg, equivalent to current formulation.

Note: The LEN target concentration of 24 ng/mL was calculated using observed antiviral activity and corresponds to a mean IQ ≥6 (range, 6.2–20.3) ng/mL.

Figure 2. Predicted PK of LEN Dosing in Phase 2/3 Studies (Begley et al)2,4

aDose originally presented as 900 mg, equivalent to current formulation.

bEnd of oral PK initiation period.

PK Study of Simplified LEN Regimen Compared With Phase 2/3 LEN Regimen in Healthy Volunteers3

Study design

A phase 1, open-label, multicohort study was conducted to compare the PK and evaluate the safety and tolerability of LEN following a phase 2/3 regimen (Cohort 1) and a simplified regimen (Cohort 2) in healthy volunteers (Figure 3). PK samples were collected before dosing began through at least Day 197 to cover three to five half-lives. Safety parameters, including AEs, were monitored throughout the study in both treatment groups. The key baseline demographics and characteristics are presented in Table 1.

Figure 3. Study Design (Jogiraju et al)3

Table 1. Key Baseline Demographics and Characteristics (Jogiraju et al)3

Results

In the phase 2/3 regimen group, the mean plasma LEN concentration was maintained above the target IQ4 of 15.5 ng/mL from 2 hours after the administration of oral LEN on Day 2 through Day 197. The median Tmax was approximately 85 days after administration of the SUBQ dose on Day 15. In the simplified regimen group, the mean plasma LEN concentration exceeded the target IQ4 of 15.5 ng/mL at 2 hours after the administration of oral LEN on Day 2 and was consistently maintained above the target IQ4 during the dosing interval. The median Tmax occurred approximately 70 days after administration of the SUBQ dose on Day 1. An overlay of the LEN concentrations for the two treatment regimens is presented in Figure 4.

Figure 4. LEN Plasma Concentration After Phase 2/3 and Simplified Dosing Regimens (Jogiraju et al)3

LEN PK parameters were generally comparable between cohorts (Table 2).

Table 2. PK Parameters of LEN Phase 2/3 Regimen and Simplified Regimen
(Jogiraju et al)3

Safety

Overall, LEN was well tolerated in both regimens, and there were no Grade 3 or 4 AEs or serious AEs. Injection site reactions were the most common AEs. No deaths were reported.

References

1. Enclosed, Gilead Sciences Inc. SUNLENCA® (lenacapavir) tablets, for oral use. SUNLENCA® (lenacapavir) injection, for subcutaneous use. U.S. Prescribing Information. Foster City, CA.
2. Begley R, Lutz J, Rhee M, et al. Lenacapavir Sustained Delivery Formulation Supports 6-Month Dosing Interval [Poster PEB0265]. Paper presented at: AIDS 2020: 23rd International AIDS Conference Virtual; 06-10 July, 2020.
3. Jogiraju V, Graham H, West S, et al. Pharmacokinetics of a Simplified Subcutaneous Lenacapavir Regimen Versus Phase 2/3 Regimen [Poster PESUB22]. Paper presented at: AIDS 2022; 29 July-2 August, 2022; Montreal, Quebec, Canada.
4. Gilead Sciences Inc. Data on File.

Abbreviations

AE=adverse event
AUC=area under the curve
Clast=concentration at last observed time point
Cmax=maximum observed drug concentration
CV=coefficient of variation
IQ=inhibitory quotient
LEN=lenacapavir
PK=pharmacokinetic(s)
SUBQ=subcutaneous(ly)
Tlast=time of last observed concentration
Tmax=time of maximum drug concentration
 

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Sunlenca US Prescribing Information available at:
http://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
 https://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

Data Privacy

The Medical Information service at Gilead Sciences may collect, store, and use your personal information to provide a response to your medical request. We may share your information with other Gilead Sciences colleagues to ensure that your request is addressed appropriately. If you report an adverse event or concern about the quality of a Gilead or Kite product, we will need to use the information you have given us in order to meet our regulatory requirements in relation to the safety of our medicines.

It may be necessary for us to share your information with Gilead’s affiliates, business partners, service providers, and regulatory authorities located in countries besides your own. Gilead Sciences has implemented measures to protect the personal information you provide. Please see the Gilead Privacy Statement (www.gilead.com/privacy-statements) for more information about how Gilead handles your personal information and your rights. If you have any further questions about the use of your personal information, please contact privacy@gilead.com.

SUNLENCA, GILEAD, and the GILEAD logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
© 2024 Gilead Sciences, Inc.