Gilead Sales Surge Masks Thin Evidence for Trodelvy Combo and Bixlenvo

Gilead Reports Strong Q3 2026 Financials and Key Regulatory Approvals

Gilead Sciences reported robust third-quarter 2026 financial results, with total product sales increasing 13% year-over-year to $8.3 billion. Product sales excluding Veklury rose 16% to $8.2 billion, driven by significant growth in HIV products (up 18% to $6.2 billion), Trodelvy (up 42% to $506 million), and Livdelzi (up 13% to $203 million). Biktarvy sales increased 10% to $4.1 billion, and Descovy sales surged 49% to $1.0 billion. The company also raised its full-year 2026 base business revenue guidance. Key updates include FDA approval for Bixlenvo™ for HIV treatment and EC marketing authorization for Trodelvy in combination with Keytruda for mTNBC.

• Gilead delivered its strongest year-over-year base business growth in over a decade, with total product sales reaching $8.3 billion, a 13% increase from Q3 2025. This strong performance led to an upward revision of the full-year 2026 base business revenue guidance, reflecting the robust and diverse growth across its portfolio, particularly in HIV and Oncology.
• The company's growth was primarily fueled by its HIV portfolio, which saw an 18% increase to $6.2 billion, including Biktarvy sales rising 10% to $4.1 billion and Descovy sales jumping 49% to $1.0 billion. Additionally, oncology product Trodelvy experienced a 42% sales increase to $506 million, and Livdelzi contributed to a 13% rise in the Liver Disease portfolio.
• Gilead achieved significant regulatory milestones, including U.S. FDA approval for Bixlenvo™ (bictegravir/lenacapavir) as a complete single-tablet regimen for virologically suppressed HIV adults. The company also secured European Commission marketing authorization for Trodelvy in combination with Keytruda for unresectable locally advanced or metastatic triple-negative breast cancer, expanding its market presence and therapeutic options.

Bixlenvo's Approval: Addressing Unmet Needs in HIV Treatment

Current combination antiretroviral therapy offers prolonged and maximal viral suppression and preservation of the immune system, but complete HIV elimination remains compromised and implies the need for life-long combination antiretroviral therapy. Inadequate adherence continues to be one of the most frequent reasons for poor treatment outcomes and lack of sustained treatment benefits, alongside drug resistance, toxicities, and viral persistence.

• Adherence and regimen complexity: Specific drug-related factors that influence adherence include pill burden, dosing frequency, food requirements, and acute tolerability and safety concerns, with additional barriers related to mental health and substance abuse and access to health care. Lower pill burden was associated with both better adherence and virological suppression, and adherence was modestly higher in once-daily regimens than twice-daily regimens (weighted mean difference = 2.55%; 95% confidence interval [CI], 1.23 to 3.87; P = .0002).

• Drug resistance and need for sustained suppression: Mutations of protease genes accelerated by low fidelity of reverse transcriptase yield drug resistant mutants of reduced affinities for the inhibitors. Most of the drug resistant virus strains are against raltegravir, some are cross-resistant to elvitegravir, and concerns include the low barrier against resistance of raltegravir, limited penetration of some PIs into the CNS and the unknown impact of integrase polymorphisms seen more commonly in non-B subtype HIV-1.

• Class-specific adverse effects and long-term morbidities: Nucleoside/nucleotide reverse transcriptase inhibitors are associated with lactic acidosis, lipodystrophy, and hyperlipidemia; non-nucleoside reverse transcriptase inhibitors are associated with neuropsychiatric symptoms, rash, liver toxicity, and lipid abnormalities; and protease inhibitors are associated with gastrointestinal intolerance and glucose and lipid abnormalities. Long-term morbidity related to antiretroviral therapy includes liver, renal, glucose, and lipid abnormalities, and cardiovascular and bone disease, with tenofovir associated with nephrotoxic drug effects including decline in glomerular filtration rate, proximal tubular damage, and acute kidney injury, and bone mineral density loss.

• Drug-drug interactions and monitoring burden: Non-nucleoside reverse transcriptase inhibitors and protease inhibitors are primarily metabolized through the cytochrome P450 system, and as a result have numerous drug-drug interactions, while information about drug interactions for maraviroc and raltegravir is limited. Monitoring for adverse effects includes a complete blood count and comprehensive metabolic profile every three to six months, a lipid profile and urinalysis for proteinuria annually, and dual energy x-ray absorptiometry should be considered in patients older than 50 years.

• Viral reservoirs, residual viraemia and lifelong therapy: Frequent administration of high doses of multiple drugs, their inefficient ability to reach the viral reservoirs in adequate doses, and the development of drug resistance compromise complete HIV elimination. A latent viral reservoir that resides in resting CD4 T cells represents a major barrier for eradication, with residual viraemia in those with plasma HIV RNA <50 copies/mL and chronic immune activation that probably underlies excess morbidity and mortality.

Lenacapavir's Global Impact on HIV Prevention and Access

Between 2003 and 2023, the annual number of new HIV infections declined globally, from 2·85 million (95% uncertainty interval [UI] 2·76-2·96) to 2·06 million (1·88-2·29). The age-standardized incidence rate also decreased globally, from 37·59 cases per 100,000 in 1990 to 25·24 cases per 100,000 in 2019, with 1.7 million people becoming newly infected with HIV in 2019.

The number of people living with HIV rose from 26·3 million (25·5-27·3) in 2003 to 42·4 million (40·3-44·4) in 2023, reflecting improved survival associated with ART expansion. HIV prevalence, HIV-associated mortality, and DALYs increased globally from 1990 to 2019.

Although females continued to have higher prevalence of HIV than males in 2023 (23·4 million [22·2-24·6] vs 19·1 million [17·6-20·5]), the gap in incidence between females and males has substantially declined. In India, age-standardized incidence, prevalence, mortality, and DALY rates of HIV were reportedly higher in males vis-à-vis females for all years between 1990 and 2019.

Navigating the Evolving HIV Treatment Landscape

Long-acting cabotegravir plus rilpivirine has moved from investigational maintenance to established alternative to daily oral therapy in virologically suppressed adults. In the pooled ATLAS (NCT02951052) and FLAIR (NCT02938520) analysis, monthly injections of CAB + RPV LA were noninferior to daily oral current antiretroviral regimen for maintaining HIV-1 suppression at week 48, with 7 individuals in each arm (1.2%) developing confirmed virologic failure. ATLAS-2M (NCT03299049) showed cabotegravir plus rilpivirine long-acting every 8 weeks was noninferior to dosing every 4 weeks with HIV-1 RNA ≥50 copies per mL in 2% vs 1% and adjusted treatment difference of 0·8 (95% CI -0·6-2·2) at week 48, with durability through week 96 with 475 (91%) of 522 in the every 8-week group and 472 (90%) of 523 in the every 4-week group maintaining HIV-1 RNA less than 50 copies per mL. In parallel, 2-drug oral simplification with dolutegravir (DTG) + lamivudine (3TC) demonstrated durable maintenance: in TANGO (NCT03446573) the proportion with HIV-1 RNA ≥50 copies/mL at week 48 was 0.3% (1/369) with DTG/3TC vs 0.5% (2/372) with a tenofovir alafenamide-based regimen (adjusted treatment difference [95% confidence interval], -0.3 [-1.2 to .7]), and in PASO-DOBLE the difference in HIV RNA ≥50 copies per mL between dolutegravir and lamivudine (six [2%] of 277) and bictegravir, emtricitabine, and tenofovir alafenamide (two [1%] of 276) was 1·4% (95% CI -0·5 to 3·4; p=0·16).

For heavily treatment-experienced adults with multidrug-resistant HIV-1, first-in-class agents added to an optimised background regimen have produced high suppression rates. In the ongoing international phase 2/3 trial at 42 sites (ClinicalTrials.gov, NCT04150068), subcutaneous lenacapavir 927 mg every 26 weeks after oral lead-in (600 mg, days 1 and 2; 300 mg, day 8) with an optimised background regimen resulted in cohort 1 having 30 of 36 participants (83%, 95% CI 67-94) with less than 50 HIV-1 RNA copies per mL and 31 of 36 participants (86%, 71-95) with less than 200 HIV RNA copies per mL at week 52, while nine participants (four in cohort 1, five in cohort 2) had emergent lenacapavir resistance and four resuppressed (HIV-1 RNA <50 copies per mL) while maintaining lenacapavir use. Real-world cohorts support durability: in the US OPERA cohort of 116 adults the cumulative probability of maintaining suppression to <200 copies/mL was 92% [95% confidence interval (CI): 80, 96] among those with baseline <200 copies/mL and 73% (95% CI: 59, 86) achieving suppression among those with baseline ≥200 copies/mL, and in LENAddOn across 19 centers in France lenacapavir continuation was 94.8% (95% CI, 87.2-98.6) at W26 and 81.8% (71.4-89.7) at W52 with last measured pVL <200 cp/mL in 72/77 participants (93.5%) and <50 cp/mL in 61/77 (79.2%). For fostemsavir, matching-adjusted indirect comparison showed fostemsavir and OBT (adjusted, N=126) associated with significantly higher odds of virologic suppression vs OBT from BENCHMRK-1/-2 (OR = 3.26; 95% CI, 2.08-5.11; P < 0.001) at week 96.

The landscape has further expanded to persons with viremia and adherence challenges and to investigational once-daily 2-drug single tablets. In LATITUDE (NCT03635788) among persons with inadequate adherence to ART, monthly injections of long-acting cabotegravir-rilpivirine were superior to standard oral ART with cumulative incidence of regimen failure by week 48 of 22.8% in the cabotegravir-rilpivirine group and 41.2% in the standard-care group (difference, -18.4 percentage points; 98.4% confidence interval [CI], -32.4 to -4.3; P = 0.002). In a multicenter randomized study of direct initiation in oral ART-experienced people with HIV-1 RNA of at least 200 copies per milliliter, viral suppression to less than 200 copies per milliliter at Week 24 was achieved in 88.0% (22/25) in the immediate LA CAB+RPV group versus 55.0% (11/20) in the delayed switch group (relative risk for failure to achieve viral suppression, 0.27; 95% CI, 0.08-0.86; p = 0.026). Switch to fixed-dose doravirine and islatravir maintained suppression in virologically suppressed adults: doravirine (100 mg) and islatravir (0·75 mg) had zero of 336 participants vs five (1·5%) of 336 on baseline ART with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 (difference -1·5, 95% CI -3·4 to -0·3) (NCT04223778), and doravirine (100 mg) and islatravir (0·25 mg) had viral loads of 50 copies per mL or higher in five (1·4%) of 366 participants versus nine (4·9%) of 185 on baseline ART (difference -3·6% [multiplicity-adjusted 95% CI -7·8 to -0·8]) (NCT05631093).