SUNLENCA (lénacapavir sodique) - VIH1 multirésistante aux médicaments

Key points

Approval of reimbursement, in association with one or more other antiretrovirals, for the treatment of multiresistant HIV-1-infected adults for whom it is otherwise impossible to set up a suppressant antiretroviral treatment regimen.

Therapeutic improvement?

Therapeutic improvement, in the same way as RUKOBIA (fostemsavir) in the care pathway.

Role in therapeutic strategy?

HIV treatment is well standardised and the subject of national and international guidelines. The therapeutic combinations recommended as a first-line approach include tritherapy with 3 highly active agents associating 2 nucleoside reverse transcriptase inhibitors [NRTIs] + a third agent (1 protease inhibitor [PI], 1 non-nucleoside reverse transcriptase inhibitor [NNRTI] or 1 integrase inhibitor [INI]) or bitherapy based on dolutegravir + lamivudine (DOVATO).

For patients with established virological failure, the choice of the new treatment is ideally discussed during a multidisciplinary review meetings including clinicians, a virologist, and pharmacologist. The opinion of an experienced team in the treatment of these patients is key in contexts where the therapeutic options appear to be limited. Other than in specific cases, treatment interruptions are not advisable. The optical treatment regimen includes three active medicinal products, based on treatment history and cumulative genotype. ARVs that can be considered as active are those

belonging to a hitherto unused class or belonging to a previously used class, but with current and cumulative resistance genotype(s) suggesting that the ARV is active.

It is not recommended to introduce a new treatment only including a single active medicinal product, as it would lead to the rapid selection of new resistance mutations. After changing antiretroviral treatment for virological failure, early monitoring (after one month) of the viral load (LV) and the tolerance of the new treatment is required.

Role of the medicinal product

SUNLENCA (lenacapavir) is a last-resort option, in association with other suitable antiretrovirals, for the treatment of multiresistant HIV-1-infected patients, for whom virological suppression cannot be obtained with the antiretrovirals currently available.

The other treatments that have been granted a marketing authorisation as a last-resort treatment like SUNLENCA (lenacapavir) include the proprietary medicinal products TROGARZO (ibalizumab) and RUKOBIA (fostemsavir), recently assessed by the Committee. TROGARZO (ibalizumab) is administered by intravenously every two weeks, unlike RUKOBIA (fostemsavir) and SUNLENCA (lenacapavir) which have the advantage of being administered orally twice-daily and subcutaneously every 26 weeks, respectively. In some cases, these medicinal products have been used in association in the CAPELLA clinical study (1 patient in the study cumulating TROGARZO (ibalizumab) and RUKOBIA (fostemsavir)).

Special recommendations

Considering the product characteristics and the complexity of the treatment of a patient in a multiple failure context, the Committee recommends restricting the prescription of SUNLENCA (lenacapavir) to medical practitioners experienced in the treatment of patients with multiresistant infection and on the basis of virological data and treatment history, and after documented proposal discussed in a multidisciplinary review meeting.

It is necessary to account for the fact that perfect treatment compliance is essential, in view of the low genetic barrier to resistance and the very long half-life of the product which is a source of particular concern. The product must also be used in association with an optimised antiretroviral treatment in order to minimise the risk of the emergence of new resistances.

Indeed, it is not possible to rule out a risk of selection (and potential transmission) of resistance in the event of poor compliance with the optimised basic treatment (giving rise to a risk of functional monotherapy with lenacapavir) or treatment interruption without rapidly setting up a suppressant regimen.