GlaxoSmithKline on Tuesday made its case for an experimental two-drug regimen of its HIV drugs dolutegravir and lamivudine, presenting detailed data from two Phase 3 trials comparing the doublet to a three-drug cocktail in previously untreated HIV patients.
Results from the studies, called GEMINI 1 and 2, showed GSK’s doublet to be as effective in controlling levels of the HIV virus as the three-drug regimen containing Gilead Sciences’ competing therapy Truvada — data that GSK hopes will convince physicians to more widely consider two-drug combinations.
“For the last 15 [to] 20 years, the standard of care for HIV has revolved around three-drug regimens,” said Pedro Cahn, the principal investigator for the studies, in a July 24 statement released by GSK. “The GEMINI studies show that we can get the efficacy of three drugs in a two-drug regimen with the tolerability and drug interaction profile of [dolutegravir] and [lamivudine].”
GSK is locked in competition with rival Gilead for control of the HIV market, with each drugmaker advancing new options aimed at better controlling the virus.
The British drugmaker’s approach has focused on establishing the safety and efficacy of two-drug regimens. Last fall, the Food and Drug Administration approved Juluca (dolutegravir/rilpivirine) for patients who are already virologically suppressed on antiretroviral therapy.
Two-drug combos offer a simpler regimen for patients who receive chronic treatment to control HIV, and have the potential to reduce drug-drug interactions and long-term exposure to multiple therapies.
Results from the GEMINI studies, which were declared successful in June, give GSK’s majority-owned subsidiary ViiV Healthcare the data needed to seek regulatory approval of a second doublet, this one pairing the active ingredient in Tivicay (dolutegravir) with lamivudine.
In a pooled analysis, 91% of patients receiving the doublet achieved HIV control, defined as plasma HIV-1 RNA levels of less than 50 copies per milliliter, by week 48. That compared to 93% of those given the triplet — well within the non-inferiority margin of 10% allowed by the study.
Comparison of GSK doublet versus TDF-containing triplet, % of treatment-naive patients achieving HIV control
|Gemini 1||Gemini 2||Pooled|
|Dolutegravir + lamivudine||90%||93%||91%|
|Dolutegravir + TDF + emtricitabine||93%||94%||93%|
Note: Study allowed for a 10% non-inferiority margin. TDF = tenofovir disoproxil fumarate SOURCE: GlaxoSmithKline, study abstract
Viral suppression appeared similar in patients with both higher and lower baseline viral loads. Notably, virological failure was less than 1% in both studies and, of those, none developed treatment-emergent resistance to treatment.
Results are only out through 48 weeks, however. Physicians are likely to want data on the development of resistance through two to three years, analysts noted when GSK announced the studies succeeded in June.
Drug-related adverse events were less frequent in the two-drug regimen arm, at 18%, than the 24% rate seen in the triplet arm.
GSK’s ViiV plans to submit an application for approval later this year. Even if ViiV secures an OK for the two-drug regimen studied in GEMINI, though, it could face an uphill battle to wrest market share away from Gilead in new-to-treatment patients.
Gilead’s new once-daily three-drug tablet, approved in February as Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) for treatment-naive HIV adults, has rapidly established its position on the market.
Prescription data from Iqvia cited by Leerink, an investment firm, show on average 2,400 new-to-brand prescriptions are being written for the drug each week over the month ending July 13.
Juluca, on the other hand, has averaged only about 350 new-to-brand prescriptions per week over the same period.
“It’s early days for the increased competition we are seeing within HIV in the US, but initial indications are encouraging and we continue to gain share,” said GSK CEO Emma Walmsley on an earnings conference call in April.
July 24, 2018