GSK's Dovato Demonstrates Non-Inferior Efficacy to Gilead’s Biktarvy in Head-to-Head HIV Trial, Highlights Favorable Weight Profile

Recently, at the AIDS 2024 conference held in Munich, GSK shared the head-to-head trial results of its Dovato compared with Gilead Sciences' Biktary in treating HIV.

In this 48-week PASO DOBLE study,Compared with Biktary, Dovato demonstrated non-inferior efficacy in HIV-infected patients who switched to Dovato.Both maintained RNA-based suppression, with Biktarvy's advantage difference at 1.4%, well within the FDA’s non-inferiority margin. In the active control group, one participant experienced confirmed virologic failure (defined as an initial HIV-1 RNA ≥50 copies/mL followed by a subsequent HIV-1 RNA ≥200 copies/mL) within 48 weeks, whereas no patients in the Dovato group had this occurrence.

It is worth mentioning that during the 48-week trial period,The weight gain in the Dovato group was significantly lower than that in the active control group. Nearly 30% of patients in the Biktarvy group experienced weight gain exceeding 5%, compared to 20% in the Dovato group.Treatment-related weight gain is a common phenomenon among AIDS patients, thus the trial results are highly significant for patients.

PASO DOBLE is an open-label, randomized, multicenter Phase 4 clinical trial designed to compare the efficacy of Dovato and Biktarvy, two antiviral therapies, in maintaining viral suppression among HIV-1 patients. A total of 553 virally suppressed HIV patients switched to either Dovato (n=277) or the active comparator drug (n=276). Participants included those on multi-tablet regimens, requiring pharmacokinetic enhancers, or facing potential drug toxicity accumulation, indicating that their treatment regimens could be further optimized.

Dovato is a fixed-dose combination tablet consisting of dolutegravir (50mg) and lamivudine (300mg). It was first approved by the U.S. FDA in 2019 as the world's first once-daily, single-tablet, two-drug regimen (2DR) for the treatment of adult HIV-1 patients with no history of antiretroviral (ARV) therapy or as a replacement for the current ARV regimen in patients who have achieved virological suppression (HIV-1 RNA <50 copies/mL) through a stable ARV regimen, without a history of treatment failure and with no known resistance to any component of Dovato.

The global market for anti-HIV virus drugs has long been dominated by a few large pharmaceutical companies, with Gilead Sciences and GSK being the two most prominent. These companies possess strong product pipelines and R&D capabilities in the field of HIV treatment and prevention, exerting a profound influence on global HIV treatment and prevention strategies.

Gilead Sciences' HIV product pipeline includes several blockbuster drugs, such as Biktarvy, Genvoya, Descovy, and Odefsey, with Biktarvy being undoubtedly Gilead's best-selling drug. In 2023, the drug's total annual sales reached $11.8 billion, accounting for 44% of total product sales. Gilead’s HIV segment collectively contributed $18.715 billion in revenue.

GSK has also been deeply involved in the research and development of HIV drugs for many years. The world's first AIDS drug, Zidovudine, was developed and marketed by GSK. Later, it developed a series of cocktail therapies such as Triumeq, Combivir, Trizivir, and Epzicom/Kivexa. In 2015, ViiV Healthcare, a subsidiary of GSK specializing in HIV drug development, acquired all of BMS's HIV drugs under development for approximately $1.455 billion, further expanding its R&D pipeline.

GSK is also committed to developing longer-lasting and more convenient treatment options, such as Dovato. In 2023, GSK's Dovato revenue reached $2.3 billion. Following the FDA's expansion in April 2024 to include adolescents, GSK expects its sales to grow to $8.5 billion by 2026.

In addition to Dovato, GSK's long-acting HIV drugs also include Cabenuva, an injectable HIV treatment administered once a month. For patients, adherence to HIV treatment regimens is crucial because poor compliance can lead to viral replication and immune system damage. The once-a-month and every-other-month dosing schedules aim to help reduce some of the treatment burden and address these issues.

Gilead Sciences has also launched a fierce offensive in the long-acting market with its first-in-class long-acting HIV capsid inhibitor, Lenacapavir, which primarily inhibits HIV-1 replication by interfering with multiple critical steps in the virus lifecycle. It was initially approved for marketing in Europe in August 2022 and subsequently received FDA approval in December of the same year. It is the world’s only approved twice-yearly HIV treatment drug. Recently, Lenacapavir achieved 100% efficacy in a Phase 3 clinical trial for pre-exposure prophylaxis (PrEP) in women, marking the first time an HIV prevention drug has reached 100% efficacy in a Phase 3 clinical trial globally. This breakthrough could once again reshape the HIV drug market landscape and further solidify Gilead Sciences' leading position in the HIV therapeutics field.