rovafovir etalafenamide (GS-9131) / Gilead - LARVOL DELTA

Synthesis of rovafovir etalafenamide: Dynamic control for successful scale-up of an oxygen-releasing elimination reaction mediated by Oxone (ACS-Sp 2022) - "The reaction presented multiple control challenges, including simultaneous addition of two reagent streams, with monitoring and control of temperature and pH in a biphasic mixture, and preventing explosive oxygen levels from building in the reactor headspace. The presentation describes our evaluation of these challenges and our approach for performing this chemistry at pilot and manufacturing scale, including the development of a cyclic processing strategy that allowed us to substantially reduce processing volumes and improve reaction throughput."

Efficacy of GS-9131 Functional Monotherapy in HIV-1-Infected Adults Failing a Nucleos(t)Ide Reverse Transcriptase Inhibitor-Containing Regimen (clinicaltrials.gov) - P2; N=21; Terminated; Sponsor: Gilead Sciences; Trial completion date: Feb 2021 ➔ Dec 2019; Active, not recruiting ➔ Terminated; GS-9131 did not meet the targeted antiviral response

Clinical • Monotherapy • Trial completion date • Trial termination • Gene Therapies • Human Immunodeficiency Virus • Infectious Disease

[VIRTUAL] SUSCEPTIBILITY OF NRTI-RESISTANT HIV-2 ISOLATES TO A NEW NRTI, GS-9131 (CROI 2020) - "Regarding the 3 main resistance genotypic profiles described in HIV-2-infected patients failing NRTI-based regimens (K65R, Q151M and M184V), our data showed that isolates harbouring only K65R or M184V mutations presented moderate increases in IC50 for GS-9131, while the presence of a Q151M mutation rendered HIV-2 isolates highly resistant to GS-9131. These in vitro data suggest that GS-9131 might offer an attractive, new therapeutic opportunity for persons living with HIV-2, either at initiation of antiretroviral therapy or for second-line regimens, as it retained potential for some activity against K65R and M184V mutants."

Efficacy of GS-9131 Functional Monotherapy in HIV-1-Infected Adults Failing a Nucleos(t)Ide Reverse Transcriptase Inhibitor-Containing Regimen (clinicaltrials.gov) - P2; N=21; Active, not recruiting; Sponsor: Gilead Sciences; Recruiting ➔ Active, not recruiting; N=69 ➔ 21

Clinical • Enrollment change • Enrollment closed • Monotherapy

Efficacy of GS-9131 Functional Monotherapy in HIV-1-Infected Adults Failing a Nucleos(t)Ide Reverse Transcriptase Inhibitor-Containing Regimen (clinicaltrials.gov) - P2; N=68; Recruiting; Sponsor: Gilead Sciences; Active, not recruiting ➔ Recruiting; Trial completion date: Aug 2020 ➔ Feb 2021

Clinical • Enrollment open • Monotherapy • Trial completion date

FAVOURABLE OUTCOME OF IN VITRO SELECTIONS WITH NOVEL NRTI PRODRUG GS-9131 (CROI 2019) - "...Cord blood mononuclear cells (CBMC) and MT-2 cells were infected with clinical isolates and passaged in increasing concentrations of GS-9131 and tenofovir (TFV)...Using 3TC as a control, the M184I or V mutations rapidly arose in most viruses...The lack of emergent variants indicates that GS-9131 is a promising antiretroviral for HIV treatment, which has also been shown to be suitable for individuals harbouring NRTI mutations. Its versatility for use in combination with other drugs may provide more precise and potent options to patients with limitations due to NRTI resistance."

Preclinical

Efficacy of GS-9131 Functional Monotherapy in HIV-1-Infected Adults Failing a Nucleos(t)Ide Reverse Transcriptase Inhibitor-Containing Regimen (clinicaltrials.gov) - P2; N=68; Active, not recruiting; Sponsor: Gilead Sciences; N=11 ➔ 68

Clinical • Enrollment change • Monotherapy