Lenacapavir represents a significant advancement in HIV treatment. Marketed as Sunlenca, this medication recently received approval from the U.S. Food and Drug Administration (FDA) for managing multi-drug resistant HIV-1 infection in adults with limited treatment options.
Lenacapavir Explained
Lenacapavir is a first-in-class capsid inhibitor for HIV-1. It works by binding to the HIV-1 viral capsid protein (p24) subunits. The capsid is a protective protein shell that encases the virus’s genetic material and essential enzymes.
By disrupting the capsid, lenacapavir interferes with multiple stages of the HIV life cycle. It inhibits the transfer of viral DNA into the host cell’s nucleus, reducing proviral DNA integration. It also blocks the assembly of new viral particles and prevents their proper release from infected cells. This multi-stage interference makes lenacapavir highly potent, even against strains of HIV resistant to other drug classes.
Significance of FDA Approval
The FDA approved Sunlenca (lenacapavir) on December 22, 2022. This approval was expedited through Breakthrough Therapy Designation, Fast Track, and Priority Review pathways, given to drugs showing early evidence of substantial improvement over existing therapies for serious conditions.
This approval is important for heavily treatment-experienced adults with multi-drug resistant HIV-1 infection. These individuals often have current antiretroviral regimens failing due to resistance, intolerance, or safety concerns. Lenacapavir offers a new option for these patients.
A benefit of lenacapavir is its long-acting nature, which reduces the frequency of medication administration. Its sustained release formulation allows for less frequent dosing.
Administration and Dosing
Lenacapavir is administered through a combination of oral tablets and subcutaneous injections. Treatment begins with an initial oral loading dose phase to quickly achieve therapeutic drug levels, involving 600 milligrams (mg) as two tablets once a day on Days 1 and 2.
Following the oral doses, a subcutaneous injection regimen begins. Patients receive a 927 mg (two vials) subcutaneous injection on Day 15. For maintenance, patients receive a 927 mg subcutaneous injection every six months. Healthcare providers administer these injections into separate abdominal sites.
Patients must continue all other prescribed HIV-1 medicines as part of their regimen. If a scheduled injection is missed by more than two weeks, oral lenacapavir tablets may be taken temporarily, at 300 mg once every seven days, for up to six months until injections can resume.
Patient Eligibility and Considerations
Lenacapavir is approved for heavily treatment-experienced adults with multi-drug resistant HIV-1 infection. This includes patients whose current antiretroviral therapy is failing due to documented resistance to at least two drugs from at least three of the four main classes of antiretrovirals, or due to intolerance or safety considerations. Patients have a baseline viral load of at least 400 copies/mL and have been on a failing regimen for at least two months.
Patients must commit to the twice-yearly injection schedule and continue their concomitant oral antiretroviral therapy to maintain viral suppression and reduce the risk of viral rebound and potential drug resistance. Healthcare providers should select patients willing and able to adhere to this schedule.
Common side effects include injection site reactions and nausea. Injection site reactions, such as swelling, pain, redness, skin hardening, or lumps, are common. Less frequently, immune reconstitution inflammatory syndrome (IRIS) may occur as the immune system recovers and responds to previously hidden infections. Patients should consult their healthcare provider to determine if lenacapavir is an appropriate treatment option.