Transcript
Announcer:
Welcome to ReachMD.
This medical industry feature, titled “Two Studies on an HIV-1 Therapy,” is sponsored by ViiV Healthcare.
This presentation was originally developed to be a full audiovisual video presentation and in audio-only form may not contain the visuals needed to represent certain data. To view this information, refer to the ReachMD landing page titled “Two Studies on an HIV-1 Therapy” to view the video.
Here’s your host, Dr. Dora Martinez.
Dr. Martinez:
Hello, I’m Dr Dora Martinez, Chief Medical Officer of the Valley AIDS Council.
Today, I’d like to share the 144-week long-term data for DOVATO from the GEMINI 1 and 2 clinical trials.
DOVATO is a complete, once-daily, single-tablet regimen for treatment-naïve and virologically suppressed adult patients with HIV-1.
You may already be familiar with how DOVATO performed at 48 and 96 weeks in the GEMINI 1 and 2 trials for treatment-naïve adults. In this video, we’ll take a look at the 144-week results from those trials.
Before we get into the data, let’s review the Indication and Important Safety Information for DOVATO.
Male:
INDICATION
DOVATO is indicated as a complete regimen to treat HIV-1 infection in adults with no antiretroviral treatment history or to replace a regimen in those who are virologically suppressed on a stable regimen with no history of treatment failure or known resistance to the components of DOVATO.
IMPORTANT SAFETY INFORMATION
DOVATO contains a Boxed Warning for patients who are co-infected with hepatitis B virus. All patients with HIV-1 should be tested for the presence of HBV prior to or when initiating DOVATO. Emergence of HBV resistance has been reported with lamivudine-containing regimens. If DOVATO is used in patients with HBV co-infection, additional treatment should be considered for the appropriate treatment of chronic HBV, or use an alternative regimen.
Additionally, if you are using DOVATO in an HBV co-infected patient and discontinue treatment, severe acute exacerbation of their hepatitis B may occur. Closely monitor hepatic function.
Contraindications
DOVATO is contraindicated in patients who have had a prior hypersensitivity reaction to dolutegravir or lamivudine or in patients who are receiving dofetilide.
Warnings and precautions
Hypersensitivity reactions have been reported in persons taking dolutegravir-based regimens and were characterized by the symptoms shown here. Discontinue DOVATO immediately if a severe skin or hypersensitivity reaction develops, as a delay may result in a life-threatening reaction. Monitor and appropriately treat the patient.
Hepatotoxicity:
Hepatic adverse events, including hepatotoxicity, have been reported in patients taking dolutegravir-based regimens in persons with and without pre-existing hepatic disease. Patients with hepatitis B or C co-infection or who have had a history of elevations in their LFTs may be at increased risk of worsening of their liver function. In some cases, increases in LFTs was consistent with IRS or HBV reactivation. Patients should be monitored for hepatotoxicity.
Embryo Fetal Toxicity:
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 due to the risk of neural tube defects.
Lactic Acidosis and Severe Hepatomegaly With Steatosis:
Discontinue DOVATO if laboratory findings suggest lactic acidosis or severe hepatomegaly, including hepatomegaly with steatosis in the absence of marked transaminase elevations.
Adverse Reactions or Loss of Virologic Response Due to Drug Interactions with concomitant use of DOVATO may occur.
Immune Reconstitution Syndrome, including autoimmune disorders, has been reported with DOVATO.
Additional Important Safety Information for DOVATO will be presented later in this video.
Please click the link accompanying this video to view the full Prescribing Information, including Boxed Warning, for DOVATO.
Dr. Martinez:
As you may recall, the GEMINI 1 and 2 studies evaluated the efficacy and safety of dolutegravir 50 mg once daily plus lamivudine 300 mg once daily in treatment-naïve adult patients with HIV-1 vs the 3-drug regimen of dolutegravir + tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC).
These studies are identically designed, Phase 3, randomized, multicenter, double-blind (to Week 96, open-label from Week 96 to Week 144), noninferiority studies, with 1433 patients combined. Data are available through 144 weeks.
The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at Week 48, using the FDA Snapshot analysis with a 10% noninferiority margin. Proportion of patients with HIV-1 RNA <50 copies/mL at Week 96 and Week 144 were pre-specified secondary endpoints.
Patients included in the studies were treatment-naïve adults (≥18 years old) who had HIV-1 RNA between 1000 copies/mL to 500,000 copies/mL at screening, ≤10 days of prior antiretroviral therapy (ART), creatinine clearance ≥50 mL/min, and no severe hepatic impairment (Child-Pugh Class C). Patients with hepatitis B virus (HBV) or major resistance-associated mutations were excluded from the trials.
Baseline characteristics were similar between the 2 arms.
Stratification factors were baseline plasma HIV-1 RNA (≤100,000 copies/mL or >100,000 copies/mL) and CD4+ T-cell count (≤200 cells/mm3 or >200 cells/mm3). 140 patients on DOVATO had high baseline viral loads >100,000 copies/mL.
By now you may be familiar with the 96-week efficacy results from GEMINI 1 and 2, but did DOVATO maintain virologic suppression through 144 weeks?
First, I want to reiterate that the primary endpoint for this study was the proportion of patients with HIV-1 RNA <50 copies/mL at Week 48.
At the 48-week primary endpoint, pooled data of the intent-to-treat–exposed population demonstrated virologic suppression with DOVATO was noninferior, with 91% suppression for DOVATO vs 93% suppression for the comparator.
DOVATO provided sustained virologic suppression through Week 96 and out to Week 144. At 96 weeks, 86% and 90% of patients experienced virologic suppression in the DOVATO arm and the comparator arm, respectively. At 144 weeks, 82% of patients in the DOVATO arm and 84% of patients in the comparator arm were suppressed.
So, we can see DOVATO provided rapid virologic suppression by Week 4, with powerful results by Week 48 that were durable through Week 144.
It’s great that DOVATO kept participants suppressed through 144 weeks, but what about resistance at 144 weeks? Let’s take a look.
There were 12 participants in the DOVATO arm and 9 in the comparator arm with confirmed virologic withdrawal, or CVW.
Outside of the CVW group, 1 participant receiving DOVATO, with reported non-adherence to the separate pills of dolutegravir and lamivudine, developed treatment-emergent resistance at Weeks 132 and 144. This participant was withdrawn from the study and re-suppressed on a dolutegravir-containing regimen.
Lastly, drug-related adverse events remained consistent with the comparator.
The most common adverse drug reactions, all Grades, in patients receiving DOVATO were headache (3%), nausea (2%), diarrhea (2%), insomnia (2%), dizziness (1%), fatigue (2%), and anxiety (2%).
Discontinuation rates were similar across both treatment arms.
Now that we’ve reviewed the GEMINI 1 and 2 144-week data, which of your treatment-naïve patients might be a good fit for DOVATO?
To summarize, we will now review the key takeaways from the GEMINI 1 and 2 trials before returning to the remaining Important Safety Information.
Based on the 144-week results from the trials, DOVATO demonstrated powerful, durable efficacy— it was as effective as a dolutegravir-based 3-drug regimen at 144 weeks—and a high barrier to resistance, based on 1 case of treatment-emergent resistance through 144 weeks.
DOVATO also does not contain TDF, TAF, or abacavir.
I hope you found the content we covered today informative, as you consider DOVATO for your appropriate treatment-naïve patients with HIV-1. To learn more, visit dovatohcp.com. Thanks for watching.
Male:
Important Safety Information (continued)
Adverse reactions:
The most common adverse reactions reported with DOVATO include headache, nausea, diarrhea, insomnia, fatigue, and anxiety.
Drug interactions
Please consult the full Prescribing Information for more information on potentially significant drug interactions.
DOVATO is indicated as a complete regimen. Coadministration with other ARVs for the treatment of HIV-1 is not recommended.
Drugs that induce or inhibit CYP3A or UGT1A1 may affect levels of dolutegravir.
DOVATO should be administered 2 hours before or 6 hours after polyvalent cations such as antacids, laxatives, and sucralfate.
Alternatively, DOVATO and supplements containing calcium or iron can be taken concomitantly if taken with food.
Use in specific populations
Pregnancy:
There are insufficient data on the use of DOVATO during pregnancy to assess the risk for birth defects and miscarriage.
Advise individuals of childbearing potential of the potential risk of neural tube defects.
Lactation:
It is not recommended to breastfeed if you are HIV positive while taking DOVATO.
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.
Hepatic Impairment:
DOVATO is not recommended in patients with severe hepatic impairment.
Please see the link accompanying this video to view the full Prescribing Information, including Boxed Warning, for DOVATO.
Outro Announcer:
You’ve been listening to ReachMD.
This presentation was originally developed to be a full audiovisual video presentation and in audio-only form may not contain the visuals needed to represent certain data. To view this information, refer to the ReachMD landing page titled “Two Studies on an HIV-1 Therapy” to view the video.
This program was sponsored by ViiV Healthcare. If you missed any part of this discussion, visit ReachMD.com/industryfeature. This is ReachMD. Be Part of the Knowledge.
