ViiV HEALTHCARE ANNOUNCES POSITIVE DATA DEMONSTRATING 2-DRUG REGIMEN DOVATO IS AS EFFECTIVE AS 3-DRUG REGIMEN BIKTARVY FOR MAINTENANCE THERAPY OF HIV-1

Harmony P. Garges, M.D., MPH, Chief Medical Officer at ViiV Healthcare, said: “The results from PASO DOBLE show that Dovato demonstrated non-inferior efficacy compared to Biktarvy, and that the average weight gain for trial participants taking DTG/3TC was significantly lower than those taking BIC/FTC/TAF over the course of the year. This is a meaningful outcome, as treatment-related weight gain is an important topic for many people living with HIV. At ViiV Healthcare we're dedicated to bringing innovative HIV treatments to people living with HIV that are not only safe and effective, but also address their specific needs beyond viral suppression.”

In the PASO DOBLE clinical trial, 553 people living with HIV and virally suppressed switched treatment to either DTG/3TC (n=277) or BIC/FTC/TAF (n=276). The study population included individuals who were on therapy that could be optimised, such as multiple tablet regimens, or those containing pharmacokinetic boosting agents or drugs with cumulative toxicity, such as efavirenz or tenofovir disoproxil fumarate (TDF). The study met its primary endpoint when DTG/3TC demonstrated non-inferior efficacy versus BIC/FTC/TAF based on the proportion of participants with viral RNA ≥50 copies/mL at 48 weeks using the FDA snapshot and a 4% non-inferiority margin in the exposed intention-to-treat population.

At 48 weeks, DTG/3TC was non-inferior to BIC/FTC/TAF (risk difference between DTG/3TC [2.2%] minus BIC/FTC/TAF [0.7%] of 1.4%, 95% CI -0.5 to 3.4). One participant in the BIC/FTC/TAF arm and zero in the DTG/3TC arm had protocol-defined confirmed virological failure through week 48 (HIV-1 RNA ≥50 c/mL followed by a second consecutive HIV-1 RNA assessment ≥200 c/mL).

The study found in a key secondary endpoint that weight increased significantly more in participants who switched to BIC/FTC/TAF (adjusted mean change 1.81kg, 95% CI 1.28-2.34) than in those who switched to DTG/3TC (adjusted mean change 0.89kg, 95% CI 0.37-1.41) [difference 0.92kg, 95% CI 0.17-1.66] through week 48. Equally, the proportion of participants with weight gain greater than 5% at week 48 was significantly higher at 29.9% for BIC/FTC/TAF compared to 20% for DTG/3TC (adjusted OR 1.81, 95% CI 1.19-2.76).

Weight change with DTG/3TC did not differ between men and women or based on the previous regimen of participants, whereas the proportion of trial participants experiencing greater than 5% weight gain with BIC/FTC/TAF was approximately 45% higher than those taking DTG/3TC when switching from a regimen with abacavir (30.6% BIC/FTC/TAF vs 21.1% DTG/3TC), and about 2-fold higher when switching from a regimen with TDF (40.7% BIC/FTC/TAF vs 19.5% DTG/3TC). Safety was comparable through week 48 and consistent with known safety profiles. There were few discontinuations due to adverse events in both study arms (DTG/3TC = 1, 0.4%; BIC/FTC/TAF = 2, 0.7%), with no differences between arms.¹

Esteban Martínez, MD, PhD, Chief Executive Investigator of the PASO DOBLE study and Senior Consultant in Infectious Diseases at Hospital Clínic of Barcelona, Spain said: “The HIV treatment regimens that are commonly prescribed today are all highly effective, which makes it critical that we study the impact of these therapies beyond just viral suppression. The results from PASO DOBLE show Dovato, a 2-drug regimen, not just demonstrated the same efficacy as a 3-drug regimen, but also showed less weight gain compared to BIC/FTC/TAF through 48 weeks.”

About PASO DOBLE

The PASO DOBLE (NCT04884139) randomised clinical trial is a phase IV, open-label, randomised multicentre clinical trial evaluating the efficacy of DTG/3TC versus BIC/FTC/TAF for the maintenance of virologic suppression in people living with HIV-1, conducted in 30 sites across Spain. Virologically suppressed people living with HIV on regimens containing ≥1 pill/day, boosters, or drugs with cumulative toxicity such as efavirenz or TDF were eligible and were randomised (1:1) to switch to either DTG/3TC or BIC/FTC/TAF. The primary endpoint was the proportion of people living with HIV with RNA ≥50 copies/mL at 48 weeks (FDA snapshot, 4% non-inferiority margin) in the intention-to-treat exposed population. Secondary outcomes measured included, among others, absolute weight gain, BMI change, and the proportion of participants with weight change greater than 5%.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: PATIENTS CO-INFECTED WITH HEPATITIS B VIRUS (HBV) AND HIV-1: EMERGENCE OF LAMIVUDINE-RESISTANT HBV AND EXACERBATIONS OF HBV

All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of lamivudine-resistant HBV variants associated with lamivudine-containing antiretroviral regimens has been reported. If DOVATO is used in patients co-infected with HIV-1 and HBV, additional treatment should be considered for appropriate treatment of chronic HBV; otherwise, consider an alternative regimen.

Severe acute exacerbations of HBV have been reported in patients who are co-infected with HIV-1 and HBV and have discontinued lamivudine, a component of DOVATO. Closely monitor hepatic function in these patients and, if appropriate, initiate anti-HBV treatment.

Lactic Acidosis and Severe Hepatomegaly With Steatosis:

Fatal cases have been reported with the use of nucleoside analogs, including lamivudine. Discontinue DOVATO if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.

Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of DOVATO and other drugs may occur (see Contraindications and Drug interactions).

Immune Reconstitution Syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported with the use of DOVATO.

Adverse reactions

The most common adverse reactions (incidence ≥2%, all grades) with DOVATO were headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), fatigue (2%), and anxiety (2%).

Use in specific populations

• Pregnancy: There are insufficient human data on the use of DOVATO during pregnancy to definitively assess a drug-associated risk for birth defects and miscarriage. An Antiretroviral Pregnancy Registry has been established. Advise individuals of childbearing potential of the potential risk of neural tube defects. Assess the risks and benefits of DOVATO and discuss with the patient to determine if an alternative treatment should be considered at the time of conception through the first trimester of pregnancy or if pregnancy is confirmed in the first trimester
• Lactation: Breastfeeding is not recommended due to the potential for HIV-1 transmission, developing viral resistance in HIV-positive infants, and adverse reactions in a breastfed infant
• Females and Males of Reproductive Potential: Pregnancy testing is recommended before initiation of DOVATO. Counsel individuals of childbearing potential taking DOVATO on the consistent use of effective contraception
• Renal Impairment: DOVATO is not recommended for patients with creatinine clearance <30 mL/min. Patients with a sustained creatinine clearance between 30 and 49 mL/min should be monitored for hematologic toxicities, which may require a dosage adjustment of lamivudine as an individual component
• Hepatic Impairment: DOVATO is not recommended in patients with severe hepatic impairment (Child-Pugh Score C)

For more information, please see full US Prescribing Information for Dovato:

https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Dovato/pdf/DOVATO-PI-PIL.PDF

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