DOVATO (dolutégravir/ lamivudine)

Antiretrovirals

Opinions on drugs - Posted on Jan 22 2020

Reason for request

First assessment

Key points

Favourable opinion for reimbursement in the treatment of HIV-1 infection only in adults and adolescents above 12 years of age weighing at least 40 kg:

treatment-naive, with a CD4 count of more than 200/mm³, a viral load (VL) of less than 100,000 copies/mL and with no known or suspected resistance to either of the two drugs;
previously treated, with a stable VL < 50 copies/mL for at least one year, a CD4 count of more than 350/mm³ and with no known or suspected resistance to either of the two drugs.

Unfavourable opinion in the other populations.

What therapeutic improvement?

Slight therapeutic improvement in the care pathway for treatment-naive patients.

An alternative to JULUCA (dolutegrivir/rilpivirine) in previously treated, virologically-suppressed patients.

Role in the care pathway?

Combination therapies with at least 3 highly active agents are recommended for first-line treatment, including 2 NRTIs + a third agent (1 PI, 1 NNRTI or 1 INI).

Role of the medicinal product in the care pathway

When dual therapy is envisaged, considering the limited data in patients with a low CD4 count and in those with a high viral load, a subpopulation in which the response appears to be lower with dual therapy than with conventional triple therapy, the Committee considers that dolutegravir/lamivudine (DOVATO) dual therapy is only a treatment option in patients (above 12 years of age):

who are treatment-naive, with a CD4 count of more than 200/mm³, a VL of < 100,000 copies/mL and with no known or suspected resistance to either of the two drugs,
previously treated, with a stable VL < 50 copies/mL for at least one year, a CD4 count of more than 350/mm³ and with no known or suspected resistance to either of the two drugs.

A good long-term result depends on good compliance with treatment.

In the absence of an MA and data, dolutegravir/lamivudine dual therapy has no role in the current care pathway for patients with virologic failure or in whom the virus is resistant to integrase inhibitors and/or to other non-nucleoside reverse transcriptase inhibitors.

Special recommendations

Given current data concerning the potential risk of congenital malformation in the event of treatment with dolutegravir at the time of conception and during the first trimester of pregnancy, the Committee does not recommend dolutegravir/lamivudine duel therapy in women of childbearing potential.

When the prescription of dolutegravir is desirable for a woman of childbearing potential, she should be informed about current data concerning the potential risk of neural tube defects and the need to use effective contraception. It may be prudent to perform a pregnancy test before initiation of dolutegravir.

In addition, patients should be informed about the potential weight gain caused by dolutegravir, highlighted by patients’ associations. More significant weight gain has been observed in patients treated with DOVATO compared to those receiving triple therapy.

Clinical Benefit

Substantial

The clinical benefit of DOVATO (dolutegravir/lamivudine) is substantial only in adults and adolescents above 12 years of age weighing at least 40 kg:

who are treatment-naive, with a CD4 count of more than 200/mm³, a viral load (VL) of less than 100,000 copies/mL and with no known or suspected resistance to either of the two drugs.
previously treated, with a stable VL < 50 copies/mL for at least one year, a CD4 count of more than 350/mm³ and with no known or suspected resistance to either of the two drugs.

Insufficient

The clinical benefit is insufficient to justify its funding by the French national health insurance system in the other populations of the MA.

Clinical Added Value

minor

Considering:

the demonstrated non-inferiority of dolutegravir + lamivudine dual therapy compared to conventional triple therapies, in treatment-naive patients and in previously treated patients with an undetectable viral load (< 50 copies/mL) and without a history of failure or resistance in terms of immunovirological response,

the high genetic resistance barrier of dolutegravir (absence of resistance observed in studies),

a relatively favourable safety and drug interaction profile,

the reduced drug exposure; which should improve the long-term toxicity related to triple therapies based on 3 or 4 medicinal products,

the transposability of the results, which is limited in patients with a low CD4 count (≤ 200 cells/mm³) and those with a very high viral load (> 100,000 c/ml),

the absence of comparison with dolutegravir/rilpivirine (JULUCA) dual therapy, indicated in previously treated, virologically-suppressed patients,

the Committee considers that DOVATO:

provides a minor clinical added value (CAV IV) in the treatment of HIV-1 infection in adults and adolescents above 12 years of age who are treatment-naive, with a CD4 count of more than 200/mm³, a VL of < 100,000 copies/mL and with no known or suspected resistance to either of the two drugs,

no clinical added value

provides no clinical added value (CAV V) in the treatment of patients infected with HIV-1, who are previously treated and virologically-suppressed, compared to the proprietary medicinal product JULUCA.