General Information

Sunlenca (lenacapavir) is a human immunodeficiency virus type 1 (HIV-1) capsid inhibitor.

Sunlenca is specifically indicated for use 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 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.

Recommended dosage – Initiation with one of two options followed by once every 6-months maintenance dosing. Tablets may be taken without regard to food.

OPTION 1

Treatment Time

Dosage of Sunlenca: Initiation

Day 1

927 mg by subcutaneous injection (2 x 1.5 mL injections) 600 mg orally (2 x 300 mg tablets)

Day 2

600 mg orally (2 x 300 mg tablets)

Dosage of Sunlenca: Maintenance

Every 6 months (26 weeks) from date of last injection +/-2 weeks

927 mg by subcutaneous injection (2 x 1.5 mL injections)

OPTION 2

Treatment Time

Dosage of Sunlenca: Initiation

Day 1

600 mg orally (2 x 300 mg tablets)

Day 2

600 mg orally (2 x 300 mg tablets)

Day 8

300 mg orally (1 x 300 mg tablet)

Day 15

927 mg by subcutaneous injection (2 x 1.5 mL injections)

Dosage of Sunlenca: Maintenance

Every 6 months (26 weeks) from date of last injection +/-2 weeks

927 mg by subcutaneous injection (2 x 1.5 mL injections)

Missed Dose

During the maintenance period, if more than 28 weeks have elapsed since the last injection and if clinically appropriate to continue Sunlenca treatment, restart the initiation dosage regimen from Day 1, using either Option 1 or Option 2

Mechanism of Action

Sunlenca (lenacapavir) is a multistage, selective inhibitor of HIV-1 capsid function that directly binds to the interface between capsid protein (p24) subunits in hexamers. Lenacapavir inhibits HIV-1 replication by interfering with multiple essential steps of the viral lifecycle, including capsid-mediated nuclear uptake of HIV-1 proviral DNA (by blocking nuclear import proteins binding to capsid), virus assembly and release (by interfering with Gag/Gag-Pol functioning, reducing production of capsid protein subunits), and capsid core formation (by disrupting the rate of capsid subunit association, leading to malformed capsids).

Clinical Trial Results

The FDA approval of Sunlenca was based on data from the Phase 2/3 CAPELLA trial, which evaluated lenacapavir in combination with an optimized background regimen in people with multi-drug resistant HIV-1 who are heavily treatment experienced. CAPELLA participants had undergone previous treatment with a median of nine antiretroviral medications. The study enrolled 36 adults who were randomized 2:1 to receive oral lenacapavir or placebo for 14 days, in addition to continuing their failing regimen (functional monotherapy). Of the 24 people randomized to the lenacapavir group, the median baseline viral load was 4.2 log10 copies/mL and 67% had a CD4 count of less than 200 cells/uL. A statistically significant greater proportion of participants receiving lenacapavir met the primary endpoint of a viral load reduction of at least 0.5 log10 copies/mL from baseline compared with those receiving placebo at the end of the 14-day functional monotherapy period (88% vs. 17%). Additionally, the lenacapavir group achieved a statistically significant greater mean change in viral load versus the placebo group (-1.93 log10 copies/mL vs. -0.29 log10 copies/mL).