Approved in Europe and the United States, lenacapavir is a first-in-class, long-acting HIV-1 capsid inhibitor for the treatment of multi-drug resistant (MDR) HIV in people who have been heavily treated, a patient population with unmet medical need. Also currently being investigated to treat HIV and for pre-exposure prophylaxis (PrEP), its infrequent dosing and self-administration will likely make it a favored choice in a population with treatment adherence challenges.

About lenacapavir

  1. Gilead Sciences Inc.
  2. Long-acting HIV-1 capsid inhibitor
  3. Twice yearly subcutaneous or oral administration to treat MDR HIV infection
  4. Also being studied to treat HIV and as PrEP
  5. ~38.4 million people had HIV globally in 2021.
  6. Only 6 countries globally have achieved <10% HIV drug resistance rates in long-term treated adults.

Why is it a drug to watch?

Lenacapavir inhibits HIV-1 at multiple stages during its lifecycle (capsid assembly, transport and disassembly), differentiating it from most other antivirals that target only one stage of viral replication and opening a new avenue for developing long-acting therapies for people living with or at risk of HIV.

  1. It has no known cross resistance to other current drug classes.
  2. Its multitarget inhibitory effect also presents a low risk of triggering drug resistance.
  3. U.S. FDA and European Commission approvals were supported by data from the phase 2/3 CAPELLA study:
    • Lenacapavir assessed in combination with an optimized background regimen in heavily treatment-experienced people with MDR HIV, a patient population with significant unmet need
    • Undetectable viral load (<50 copies/mL) achieved by 83% of participants at week 52
    • Mean increase in CD4 count of 83 cells/µL
  4. Other phase 3 studies are ongoing and planned to assess lenacapavir for PrEP:
    • PURPOSE 1: lenacapavir and emtricitabine/tenofovir alafenamide for PrEP in adolescent girls and young women at risk of HIV infection
    • PURPOSE 2: lenacapavir for PrEP in cisgender men, transgender women, transgender men and gender non-binary individuals who have sex with partners assigned male at birth
  5. In March 2021, Gilead Sciences Inc. and Merck entered an agreement to co-develop and co-commercialize lenacapavir and islatravir (nucleoside reverse transcriptase translocation inhibitor) into a two-drug regimen.

Review and approval status

August 2022:
For adult patients with MDR HIV infection:
• Marketing authorization: EC

December 27, 2022:
• For heavily-treatment-experienced adult patients with MDR HIV-1 infection: Marketing authorization: U.S.

Actual and expected launch:
2022: Europe
2023: United States
2028: Japan

Patents estimated to expire beginning in 2028

How will lenacapavir impact the market for HIV?

Lenacapavir is expected to have a competitive advantage given its convenient, twice-yearly administration that will help address treatment burden and social stigma. Rapid uptake is therefore anticipated, and it is predicted that lenacapavir will account for more than one-half of yearly sales of long-acting regimens by 2031.

What gaps in treatment does lenacapavir fill?

MDR is a growing issue for people living with HIV, creating challenges with disease management for the patients themselves as well as in achieving global goals of ending the HIV epidemic. There is significant unmet medical need in particular for heavily treatment-experienced people with MDR HIV. With its convenient self-administration method and twice-yearly dosing, lenacapavir could overcome the lack of adherence to HIV therapies that can occur due to the burden of daily dosing (pill fatigue) and stigma related to HIV. The lower gastrointestinal toxicity, reduction in related side effects and fewer drug-drug interactions will also make lenacapavir more tolerable for many people living with HIV.

What hurdles might it need to overcome to reach blockbuster status?

Given the relatively small sample size and short length of the phase 2/3 CAPELLA study, long-term data are needed to convince health care providers to prescribe lenacapavir in patients with MDR, especially because of the robust, long-term data for RUKOBIA (ViiV Healthcare) in the same population. For development as a long-acting regimen for HIV treatment (not in the presence of MDR), a good partner agent is needed. The most advanced combination to date (lenacapavir + Merck’s islatravir) was temporarily paused due to a dose-dependent decrease in white blood cell counts, but phase 2 trials are expected to resume. Although expected to be approved for HIV PrEP in 2025, lenacapavir will need to demonstrate better safety and efficacy than currently available long-action options. Pricing will also play a role in uptake as PrEP, since DESCOVY® will also go off patent in 2025, and pricing will likely become competitive.

expected sales in 2027
probability of success for lenacapavir in Japan.

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