Lenacapavir submitted to FDA as long-acting treatment for MDR HIV
Simon Collins, HIV i-Base
On 28 June 2021, Gilead Sciences submitted a new drug application to the US FDA for lenacapavir as a treatment for HIV in people with multiple drug resistance MDR. 
An application to the EMA in Europe will follow in the next months, with final decisions expected to take a year. Submission to the MHRA in the UK is likely to follow the EU decision. Over this extended period, a limited programme will hopefully enable access for individuals in critical need, although details have not yet been released.
Lenacapavir is a capsid inhibitor, and as the first drug in a new class, will have activity against HIV that has developed resistance to other antiretroviral drugs. It need to be used in a combination with other drugs that are active in order to prevent drug resistance.
The application is based on results from the phase 2/3 CAPELLA trial presented at CROI 2021.
CAPELLA included 36 participants in a double-blind randomised placebo controlled cohort and another 36 participants that used open label lenacapavir. Lenacapavir was significantly more likely to produce a viral load reduction >0.5 log after 14 days (median reduction of 2.0 logs) and a significantly greater chance of an undetectable viral load after 4 weeks after two weeks of optimised background therapy.
Tolerability was good with the most common side effects related to injection site reactions – full details are included in the HTB report from CROI. 
Lenacapavir is a long-acting treatment that is given as a subcutaneous injection every six months.
The prospect of 6-monthly dosing for an HIV drug is astonishing: this is therefore a particularly exciting and important submission.
Lenacapavir will enable anyone with extensive drug resistance to make an effective combination as two other recently approved first-in-class drugs (fostemsavir and ibalizumab) have also been recently approved. The long-acting formulation should considerably help cases where adherence was difficult.
Although this is a tiny dataset, the FDA must have indicated this could be sufficient for a strict MDR indication.
A regulatory decision in the EU has a timeline of an expected decision in mid-2022. Submission to the MHRA in the UK will follow EU final decision on approval.
An individual patient supply is also likely to be available for people in the UK and Ireland with MDR HIV who would be dependent on lenacapavir in their next combination. This would be decided on a case by case basis, with entry criteria likely to be similar to the CAPELLA study.
Health care professional’s should contact their Gilead medical scientist for information on whether access Individual Patient Supply is available.
This filing also marks the start of an era where extremely long-acting treatments could offer very easy options compared to taking daily oral tablets.
The depends on having other drugs to use with lenacapavir. In March 2021, Gilead announced a new partnership with Merck/MSD that will enable access to islatravir and other long-acting pipeline antiretrovirals. 
ViiV Healthcare, the third large research based company involved in HIV, also have a pipeline that includes similarly long-acting compounds in earlier stages of development.
- Gilead PR. Gilead submits new drug application to U.S. Food and Drug Administration for lenacapavir, an investigational, long-acting capsid inhibitor for the treatment of HIV-1 in people with limited therapy options. (28 June 2021).
- First results using capsid inhibitor lenacapavir against MDR HIV: potential for six-monthly ART and PrEP. HTB (1 April 2021).
- Collins S. Gilead and Merck/MSD to collaborate on long-acting HIV combination of lenacapavir and islatravir. HTB (15 March 2021).