Proved non-inferiority compared to Tenofovir based 3~4-drug complex
Decreases medication exposure frequency as well as adverse effects of a drug
The generational shift to Triumeq • implies competition with Biktarvy
The era of dual therapy for HIV begins in South Korea. GSK (Julien Samson, Vice President & General Manager) launched Dovato (Dolutegravir/Lamivudine), which is on the coverage list of health insurance.
As a result, the fierce competition between Dovato, which promotes the paradigm shift of HIV treatment, and Biktarvy (bictegravir, emtricitabine, and tenofovir alafenamide, Gilead), which lays the foundation of highly active antiretroviral therapy (HAART), is expected to heat up.
On the 23rd, GSK held a press conference at Chosun Hotel in Seoul to commemorate the launch of Dovato and announced the opening of HIV dual therapy.
Dovato is an HIV treatment developed by ViiV Healthcare, which was founded by GSK and Pfizer in 2009, and was listed on the health insurance coverage list after winning permission in Korea.
It is a single-tablet regimen (STR) and two-drug complex of Nucleoside reverse transcriptase inhibitors (NRTIs) lamivudine (3TC), which is known as dolutegravir (has a high resistance barrier among integrase strand transfer inhibitor (INSTI)) and antivirals.
Dovato has become the world’s first two-drug regimen among HIV first-line treatment by proving its non-inferiority compared to tenofovir based 3~4-drug complex in main clinical trials, despite it remains as two-drug complex without abacavir from GSK’s existing HIV drug, Triumeq (dolutegravir, abacavir, and lamivudine), a single tablet regimen.
In fact, Dovato has verified the actual safety and effectiveness of clinical setting through a number of Real World Data (RWD) of more than 5,000 infected people, including landmark studies GEMINI 1,2 and TANGO.
In GEMINI 1 and GEMINI 2 studies, a global phase III clinical trial of 1,400 new infected HIV adults identified anti-viral effects and safety profiles that are equivalent to those of the existing three-drug regimen (dolutegravir, tenofovir disoproxil fumarate (TDF), and emtricitabine).
In particular, none of the patients who showed viral failure in all treatments experienced resistance due to the treatment.
Moreover, tenofovir disoproxil fumarate (TDF), which is considered as a disadvantage of kidney and bone density, showed improved results and confirmed the benefits of the two-drug regimen.
However, since the actual competitor of Dovato is not a TDF based regimen, this study is limited in the advantages of verified two-drug therapy.
The transition from TDF to TAF is already progressing rapidly, and TDF medications almost lost their grounds.
TAF, like TDF, uses tenofovir as its core ingredient, but innovatively reduced the amount of blood exposure that quenched issues related to kidney and bone density, which are considered as disadvantages of TDF.
Meanwhile, a global phase III clinical trial Tango research proved the equivalent effect of a three-drug regimen, including tenofovir alafenamide fumarate (TAF), and further reduced the burden of weight gain.
The TANGO research evaluated the viral suppression rate for infected adults who had maintained virus suppression for more than six months with a three-drug regimen, including TAF.
The 1st efficacy evaluation variables for non-inferiority were satisfied in the proportion of infected persons who had an HIV-1 RNA level of 50 c/ml at 48-week.
In this study, GSK explained that Dovato reduced the burden of tenofovir exposure due to less weight gain compared to the TAF group.
Based on a number of these clinical results, recent guidelines for HIV treatment, including the U.S. Department of Health and Human Services (DHHS) and European AIDS Clinical Society (EACS), recommended the two-drug regimen Dovato as a first-line treatment.
In the past, HIV drugs, a size about a meal, had to be taken four times a day to survive. It was a time when it was hard to eat because of being full due to a huge dose of medication.
For this reason, HIV-infected people wish for less drug exposure as a second after the complete cure.
At the hologram press conference, Jean Van Wyk (medical director of ViiV Healthcare) said, “with the rapid development of HIV treatments, the life expectancy of infected people is increasing, and the age range of infection is getting younger in the 20s and 30s, minimizing the impact of long-term polypharmacy is the primary goal of the recent development of HIV treatments.
he introduced that “GSK and ViiV Healthcare reviewed numerous strategies, including reducing the number or capacity of ARV drugs, or discounting the use of PK booster, and focusing on unfulfilled demand for infected people who are burdened with long-term use of ARV,” and added, “Dolutegravir and lamivudine were the best combinations with similar pharmacokinetic (PK) profiles and complementary therapeutic effects with different action mechanisms.
He explained that compared to Triumeq of GSK, Dovato could maintain a strong viral suppression effect without abakavir, lightening the load of gastrointestinal and hypersensitive reactions caused by abakavir, which also eliminates the need for an anaphylactic test before HIV treatment.
However, considering the reality of Korea, which is sensitive to drug resistance, it is uncertain whether the two-drug regiment will gain as much trust as expected in the actual clinical test.
The advantage of the frequency of drug exposure (a differentiating point of Dovato) could be considered as a limitation that most of the data are compared to the old generation of TDF.
Nevertheless, Wyk was assured that “After two years of observation of 700 patients in the GEMINI study, no resistance has been found,” and “I am 100% confident that Dovato’s high resistance barrier is comparable to dolutegravir’s three-drug regimen.”
He pointed out that the patients should consult with a doctor before temporarily stopping the medication since there is a possibility of resistance when taking the drugs intermittently.
Regarding the advantages of a two-drug regimen, he believes in finding them soon as the study is in progress.
