Interventional, Multicenter, Open-label, Randomized, Non-comparative Trial Evaluating the Safety, in Terms of HBV Virological Control At 96 Weeks, of 2 Antiviral Treatment Relief Strategies, in Patients Co-infected with the HIV-1 and HBV Viruses

The main objective of this study is to evaluate at 96 weeks the safety with respect to hepatitis B control of 2 treatment reduction strategies for patients with previously controlled HIV-HBV co-infection on continuous triple therapy

Start Date01 Feb 2025

Sponsor / Collaborator-

100 Clinical Results associated with Tenofovir Disoproxil Fumarate

100 Translational Medicine associated with Tenofovir Disoproxil Fumarate

100 Patents (Medical) associated with Tenofovir Disoproxil Fumarate

6,683

Literatures (Medical) associated with Tenofovir Disoproxil Fumarate

01 May 2025·ANTIVIRAL RESEARCH

Tenofovir alafenamide promotes weight gain and impairs fatty acid metabolism-related signaling pathways in visceral fat tissue compared to tenofovir disoproxil fumarate

Article

Author: Wallace, Jennillee ; Patel, Niyati ; Naqib, Ankur ; Olali, Arnold Z ; Dulion, Bryan ; Virdi, Amber K ; Ross, Ryan D

Modern antiretroviral therapy (ART) is associated with rapid weight gain, which appears to be antiretroviral-specific. Tenofovir is a nucleoside reverse transcriptase inhibitor commonly employed as a backbone in many ART formulations. Tenofovir alafenamide (TAF) has been associated with significant weight gain in people living with HIV (PLWH) initiating ART. Interestingly, tenofovir disoproxil fumarate (TDF), has no impact on weight or may even be weight suppressive. The current study compared the impact of two tenofovir-based ART formulations on weight and adipose tissue. We utilized a humanized mouse model of HIV-infection and administered two clinically relevant ART combinations TAF/dolutegravir (DTG)/emtricitabine (FTC) and TDF/DTG/FTC. As expected, female mice treated with TAF/DTG/FTC had the greatest weight gain and fat accumulation, as measured by dual energy x-ray absorptiometry (DXA). As ART-induced accumulation of visceral adipose tissue is linked to mortality, we isolated visceral adipose tissue for targeted (qPCR) and non-targeted (RNAseq) gene expression. Mice treated with TAF/DTG/FTC had increased expression of adipocyte differentiation related genes, leptin and PPAR-γ. RNAseq revealed that while the expression patterns for both TAF/DTG/FTC and TDF/DTG/FTC treated mice were similar, there were key differences. Specifically, KEGG pathway analysis indicated that TAF/DTG/FTC treated mice showed suppression of multiple fatty acid metabolism related pathways, while TDF/DTG/FTC treated mice showed evidence for increased thermogenesis. The results suggest that weight gain associated with TAF-based ART may be due to impaired adipocyte mediated lipid handling, while suppressed weight gain with TDF-based ART may be secondary to increased browning of visceral adipocytes, although independent validation is necessary.

01 May 2025·AIDS

Reduced bone density accrual among peripubertal boys with HIV in Zimbabwe

Article

Author: Simms, Victoria ; Rowland-Jones, Sarah ; Hsieh, Anthony Y.Y. ; Kahari, Cynthia ; Jeena, Lisha ; Rukuni, Ruramayi ; Gregson, Celia L. ; Rehman, Andrea M. ; Bandason, Tsitsi ; Ferrand, Rashida A.

Objective::

To investigate bone density accrual over 1 year among peripubertal children with HIV (CWH) compared to children without infection (CWOH); and risk factors associated with bone density accrual among CWH.

Design::

A prospective cohort study in urban Zimbabwe.

Methods::

CWH on antiretroviral therapy aged 8–16 years, and CWOH, frequency-matched by age were recruited in Zimbabwe. Z-scores for height-adjusted total-body less-head bone mineral content for lean mass (TBLH-BMCLBM) and size-adjusted lumbar spine bone mineral apparent density (LS-BMAD) were calculated from dual X-ray absorptiometry (DXA) scan measurements. Linear regression compared bone density accrual by HIV status.

Results::

Of 609 participants, 492 (80.7%) completed a follow-up visit (50.2% boys, 49.6% CWH). Mean baseline age was 12.5 years. More girl CWH than CWOH were in Tanner stages I/II at baseline. Bone density accrual (Δ) adjusted for age, Tanner stage and baseline DXA Z-score was less in boy CWH than boy CWOH {adjusted mean (95% confidence interval (CI)] ΔLS-BMAD Z-score −0.14 (−0.25 to −0.02) vs. 0.01 (−0.09 to 0.12), P = 0.020, and ΔTBLH-BMCLBMZ-score −0.19 (−0.33 to −0.04) vs. 0.07 (−0.07 to 0.20), P = 0.015}, but similar in girls with and without HIV [ΔLS-BMAD Z-score 0.05 (−0.07 to 0.17) vs. −0.01 (−0.09 to 0.07), P = 0.416, and ΔTBLH-BMCLBMZ-score 0.08 (−0.07 to 0.22) vs. −0.03 (−0.12 to 0.07), P = 0.295]. Viral load greater than 1000 copies/ml and tenofovir disoproxil fumarate use were associated with less gain in LS-BMAD Z-score among boys, whereas Tanner stage IV and V were associated with greater gains in LS-BMAD and TBLH-BMCLBMZ-scores among CWH.

Conclusion::

Among boys only, CWH had impaired bone accrual, associated with high viral load and tenofovir use. Bone density gains were greater in later puberty among CWH suggesting potential to correct deficits.

01 May 2025·JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES

Brief Report: Resolution of Neuropsychiatric Adverse Events After Switching to a Doravirine-Based Regimen in the Open-Label Extensions of the DRIVE-AHEAD and DRIVE-FORWARD Trials

Article

Author: Moyle, Graeme ; Wan, Hong ; Plank, Rebeca M. ; Lahoulou, Rima ; Sklar, Peter ; Meng, Fanxia

Background::

Neuropsychiatric adverse events (NPAEs) are associated with several antiretrovirals. Doravirine (DOR), a non-nucleoside reverse transcriptase inhibitor indicated for HIV-1 treatment, does not interact significantly with known neurotransmitter receptors in vitro. First-line therapy with DOR-based regimens resulted in significantly fewer NPAEs than efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF) and similar rates to those of ritonavir-boosted darunavir (DRV/r) with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) through week 96 of the phase 3 DRIVE-AHEAD and DRIVE-FORWARD studies, respectively.

Methods::

In the DRIVE-AHEAD (NCT02403674) and DRIVE-FORWARD studies (NCT02275780), treatment-naive adults randomly received DOR/lamivudine/TDF or EFV/FTC/TDF and DOR + 2 NRTIs or DRV/r + 2 NRTIs, respectively, for a 96-week double-blind phase; afterward, participants could continue or switch to a DOR-based regimen for a 96-week open-label extension.

Results::

Overall, 269 and 233 participants in the DRIVE-AHEAD and DRIVE-FORWARD studies, respectively, switched to a DOR-based regimen. At week 96, 26 and 15 participants randomized to EFV/FTC/TDF and DRV/r + 2 NRTIs, respectively, had ongoing NPAEs, resolving by week 192 in 73% (19/26) and 40% (6/15) of participants switching to a DOR-based regimen. New-onset NPAEs were reported by 9% (25/269) and 8% (18/233) of participants; by week 192, new-onset NPAEs were resolved and/or resolving in 60% (15/25) and 61% (11/18) of participants.

Conclusions::

In both trial extensions, NPAEs persisted in 3%–4% of participants 96 weeks after switching to a DOR-based regimen, possibly representing the background rate for these events. This suggests that DOR-based therapy may be a good option for adults with baseline neuropsychiatric symptoms or those experiencing NPAEs with other antiretrovirals.

160

News (Medical) associated with Tenofovir Disoproxil Fumarate

12 Mar 2025

·pipelinereview.com

Gilead Presents New HIV Treatment and Cure Research Data at CROI 2025, Including an Investigational Long-Acting, Twice-Yearly Therapy Option

– Long-Term Outcomes Reinforce the High Efficacy of Biktarvy ® in People with HIV and HBV Coinfection – – Investigational Long-Acting, Twice-Yearly Treatment Regimen of Lenacapavir and Broadly Neutralizing Antibodies (bNAbs) Meets Primary Endpoint in Phase 2 Study and Gains Breakthrough Therapy Designation – – Late-Breaker Oral Presentation of Phase 2 Results from the First HIV Cure Clinical Trial Conducted in South Africa – FOSTER CITY, CA, USA I March 12, 2025 I Gilead Sciences, Inc. (Nasdaq: GILD) today announced the presentation of late-breaking data and multiple oral presentations from its innovative HIV treatment portfolio and pipeline at the Conference on Retroviruses and Opportunistic Infections (CROI 2025). The new findings reflect a transformative portfolio and a rapidly advancing forward-looking pipeline focused on expanding choices and enhancing outcomes for those with HIV, while continuing to reach towards a cure. “Gilead is fueling the next wave of innovation in HIV to help end the epidemic globally,” said Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head. “Our contributions to CROI spotlight our dedication to scientific discovery, reflect our commitment to addressing the diverse treatment needs and preferences of communities affected by HIV and underscore the vital importance of catalyzing research reaching towards a cure.” Biktarvy Demonstrates High Rates of Viral Suppression in People with HIV/HBV Coinfection ALLIANCE ( NCT03547908 ) is an ongoing Phase 3 study evaluating Biktarvy versus dolutegravir 50 mg (DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, F/TDF, DTG+F/TDF, in adults with HIV-1/HBV co-infection initiating treatment. The ALLIANCE trial is the first randomized clinical trial of TAF- vs TDF-based regimens in treatment naïve adults with HIV/HBV coinfection. Its goal is to evaluate treatment regimens that may effectively suppress both HIV and HBV. Previously reported results demonstrated the efficacy of both antiretroviral regimens. New outcomes were presented at CROI. Week 48 outcomes from the open-label extension phase following the 96-week randomized phase reported on the longer-term efficacy and safety of the investigational use of Biktarvy in adults with HIV/HBV coinfection initiating treatment. The newly presented data shows that Biktarvy maintained high rates of HIV-1 (95.4%) and HBV (86.6%) virologic suppression, defined as HIV RNA <50 copies/ mL and HBV DNA <29 IU/ mL, respectively, in participants (n=89) following a switch to Biktarvy after 96 weeks of treatment with DTG+ F/TDF. Study drug-related treatment-emergent adverse events (TEAEs) were reported in 19% of participants and most were mild to moderate, with zero discontinuations due to TEAEs. The most commonly reported study drug–related TEAEs were weight gain (9%) and low-density lipoprotein (LDL) cholesterol increased (3%). These data demonstrate the high rates of viral suppression by Biktarvy in adults with both HIV-1 and HBV switching their treatment to Biktarvy. The use of Biktarvy in individuals with HIV/HBV co-infection is investigational and the safety and efficacy of this use have not been established. Breakthrough Therapy Designation Awarded to Long-Acting, Twice-Yearly Investigational Treatment Combination Regimen of Lenacapavir and Broadly Neutralizing Antibodies (bNAbs) In January 2025, the FDA granted lenacapavir (LEN) with bNAbs (teropavimab [GS-5423, TAB] and zinlirvimab [GS-2872, ZAB]) Breakthrough Therapy Designation, which is intended to expedite the development of new drugs that may demonstrate substantial improvement over available therapy. LEN+TAB+ZAB (LTZ) harbors the potential to be the first long-acting combination treatment regimen with twice-yearly dosing. At CROI 2025, the primary results of a Phase 2 study evaluating the investigational combination of LTZ were presented during an oral session and featured in the press program; those data announced at CROI confirm previously presented Phase 1b results. The Phase 2 ( NCT05729568 ) open-label study from Gilead’s long-acting treatment pipeline evaluated the treatment response of participants receiving the investigational combination of LTZ. Efficacy and safety results were evaluated when virologically suppressed adults switched to LTZ every 6 months versus staying on stable baseline oral antiretroviral regimen. The study met its primary endpoint, which is the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 26 as determined by the US FDA-defined snapshot algorithm. The Week 26 data demonstrated the high efficacy of the LTZ regimen, with 96% (n=51 of 53) of participants who received LTZ and 96% (n=26 of 27) who received SBR remained virologically suppressed. CD4 cell counts also increased from baseline to week 26 in both groups, with a mean change of +23/μL (n=143) with LTZ and +69/μL (n=203) with SBR. The most common AEs with LTZ were injection site reactions related to subcutaneous LEN administration. There were no serious adverse events (AEs) related to LTZ; there were no infusion reactions related to TAB or ZAB. One participant in the SBR arm discontinued the study due to a serious treatment-related AE. Teropavimab and zinlirvimab are investigational compounds. The use of these compounds in combination with lenacapavir are investigational. They are not approved by the U.S. Food and Drug Administration or any other regulatory authority for any use, alone or in combination with lenacapavir. Their safety and efficacy are unknown. The use of lenacapavir in virologically suppressed people with HIV is investigational and the safety and efficacy of this use have not been established. Landmark HIV Cure Clinical Trial Conducted in South Africa Results from the first HIV cure trial to be conducted in South Africa, sponsored by Gilead, demonstrated that complex cure studies can be successfully conducted, alongside community, in resource-limited settings where great unmet need exists. As part of Gilead’s efforts to find a cure for HIV, the Phase 2a GS-US-382-5445 trial ( NCT05281510 ) enrolled 20 South African cisgender women from the FRESH (Females Rising through Education, Support, and Health) cohort who had received antiretroviral therapy (ART) soon after acquiring HIV and were virologically suppressed for at least 12 months. Participants received up to 10 oral doses of Gilead’s investigational TLR7 agonist, vesatolimod, every 2 weeks starting on day 0, plus IV infusions of broadly neutralizing antibodies (bNAbs) VRC07-523LS and CAP256V2LS, provided by the National Institutes of Health (NIH), on day 7. Participants began an analytical treatment interruption (ATI) on Day 35 and remained off ART until Week 48, or until they met restart criteria. Participants who reached week 48 without meeting ART restart criteria had the option of remaining off ART through the end of study follow-up at Week 60. Results presented at CROI showed the treatment combination was generally well-tolerated with no treatment-related serious adverse events (TEAEs) reported. The most common study TEAEs were infusion-related reactions (n = 18; 16 grade 1, 2 grade 2). Seventy percent of participants (n=14) met ART restart criteria. Thirty percent (n=6) remained off ART through Week 48, of which 4 remained off ART through Week 60. While the data suggest that the trial regimen alone is not sufficient as an HIV cure regimen, the mechanistic learnings will inform the development of future cure approaches. There is currently no cure for HIV or AIDS. Vesatolimod, VRC07-523LS and CAP256V2LS are investigational compounds. They are not approved by the U.S. Food and Drug Administration or any other regulatory authority for any use, alone or in combination. Their safety and efficacy are unknown. Please see below for U.S. Indications and Important Safety Information, including Boxed Warning , for Biktarvy. About Lenacapavir Lenacapavir is approved in multiple countries for the treatment of adults with multi-drug resistant HIV in combination with other antiretrovirals. The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established. The multi-stage mechanism of action of lenacapavir is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes. Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program. Lenacapavir is being developed as a foundation for potential future HIV therapies with the goal of offering both long-acting oral and injectable options with several dosing frequencies, in combination or as a mono agent, that help address individual needs and preferences of people and communities affected by HIV. Science Magazine named lenacapavir its 2024 “Breakthrough of the Year.” About Biktarvy Biktarvy is a complete HIV treatment that combines three powerful medicines to form the smallest 3-drug, integrase strand transfer inhibitor (INSTI)-based single-tablet regimen (STR) available, offering simple once-daily dosing with or without food, with a limited drug interaction potential and a high barrier to resistance. Biktarvy combines the novel, unboosted INSTI bictegravir with the F/TAF backbone. Biktarvy is a complete STR and should not be taken with other HIV medicines. U.S. Indication for Biktarvy Biktarvy (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral (ARV) treatment history or to replace the current ARV regimen in those who are virologically-suppressed (HIV-1 RNA <50 copies per mL) on a stable ARV regimen with no known or suspected substitutions associated with resistance to bictegravir or tenofovir. About Gilead HIV Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. For more than 35 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 12 HIV medications , including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to help reduce new HIV infections, and the first long-acting injectable HIV treatment medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a treatable, preventable, chronic condition for millions of people. Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships , collaborations and charitable giving, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic for everyone, everywhere. Gilead has been repeatedly recognized as one of the top two leading philanthropic funders of HIV-related programs in a report released by Funders Concerned About AIDS. SOURCE: Gilead Sciences

Clinical ResultPhase 2Phase 3Drug ApprovalBreakthrough Therapy

12 Mar 2025

·pipelinereview.com

First Clinical Data for Gilead’s Investigational Once-Yearly Lenacapavir for HIV Prevention Presented at CROI 2025 and Published in The Lancet

– Phase 1 Data Indicate Potential for Use of Once-Yearly Lenacapavir for HIV Prevention, with Plans to Launch a Phase 3 Trial in 2H 2025 – – Also at CROI: New PURPOSE 1 Data Showcasing Preference for Twice-Yearly Lenacapavir vs. Once-Daily Orals and In-Depth Look at Adolescent Pharmacokinetic, Safety and Efficacy Data – FOSTER CITY, CA, USA I Marcch 11, 2025 I Gilead Sciences, Inc. (Nasdaq: GILD) today presented the first data from its ongoing Phase 1 study investigating two novel, once-yearly formulations of lenacapavir, the company’s injectable HIV-1 capsid inhibitor, for the investigational use of HIV prevention as pre-exposure prophylaxis (PrEP). The data were presented during an oral abstract session at the Conference on Retroviruses and Opportunistic Infections (CROI 2025) and were also published today in The Lancet . Data will support the future development of once-yearly lenacapavir for PrEP, for which Gilead plans to launch a Phase 3 study in the second half of 2025. The Phase 1 study data showed that the two different formulations of once-yearly lenacapavir administered via intramuscular injection achieved and maintained plasma concentrations exceeding those associated with HIV prevention efficacy observed in the Phase 3 PURPOSE 1 trial ( NCT04994509 ) and PURPOSE 2 trial ( NCT04925752 ). The previously reported PURPOSE 1 and PURPOSE 2 data showed that twice-yearly subcutaneous lenacapavir demonstrated superiority at reducing HIV infections when compared to background HIV incidence (bHIV) and once-daily oral Truvada® (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) in a broad and geographically diverse range of people. “Gilead is continuing to innovate in our work to develop additional person-centered long-acting injectable and oral options to help people find an HIV prevention choice that is right for them,” said Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “Once-yearly lenacapavir, if approved, could become an important new HIV prevention option that could help address PrEP adherence and persistence challenges for individuals who need or want PrEP around the world.” Promising once-yearly lenacapavir for PrEP pharmacokinetic profiles over 52 weeks The Phase 1 study evaluated the pharmacokinetics, safety and tolerability of two intramuscular single-dose 5000mg lenacapavir formulations. The trial included 40 healthy adults at low risk of HIV acquisition, between the ages of 18 and 55 years, with a body mass index of less than or equal to 35.0 kg/m 2 . Lenacapavir plasma concentrations for participants remained above the 95% effective concentration for at least 56 weeks with both formulations. Furthermore, median trough concentrations of both formulations of once-yearly lenacapavir at Week 52 (57.0 ng/mL and 65.6 ng/mL) were higher than those observed with twice-yearly lenacapavir in the PURPOSE 1 and PURPOSE 2 trials at Week 26 (23.4 ng/mL). Data from the study confirmed that both once-yearly formulations of lenacapavir warrant further investigation. Safety data demonstrated both formulations of once-yearly lenacapavir for PrEP were well tolerated, with no new safety signals Once-yearly lenacapavir is being investigated as an intramuscular injection. This is different from the subcutaneous formulation of lenacapavir, which is being investigated for twice-yearly dosing. The most commonly reported adverse event for both intramuscular formulations studied was injection site pain, which was mostly mild in severity and resolved within 1 week (occurred in 80% of participants receiving formulation 1, and 75% receiving formulation 2), and was reduced by pretreatment with an ice pack. Medication-emergent adverse events were similar between the two cohorts and mostly mild to moderate in severity. New PrEP modality preference data demonstrate preference for twice-yearly lenacapavir vs. once-daily orals in PURPOSE 1 survey participants New quantitative survey data and late-breaking qualitative survey data from the PURPOSE 1 trial, evaluating twice-yearly subcutaneous lenacapavir for PrEP among cisgender women in sub-Saharan Africa, were also presented at CROI in two poster sessions. An interim analysis of surveys included 2,561 trial participants’ self-reported preferences for twice-yearly lenacapavir for PrEP injections and once-daily pills, with approximately two-thirds of survey respondents preferring twice-yearly lenacapavir at Week 52 of their trial participation, compared to fewer than one-third of respondents preferring once-daily pills. Additionally, at Week 52, most respondents (61%) reported they would feel more protected from HIV with twice-yearly PrEP injections compared with once-daily pills, and 61% of respondents also reported they would feel more confident about not missing a PrEP dose with twice-yearly injections compared with once-daily pills. Qualitative data among 108 participants also showed that respondents, particularly adolescents aged 16 and 17 years, noted that twice-yearly injections better suited their lifestyles compared with once-daily pills. New study population data from PURPOSE 1 show comparable pharmacokinetic and safety profiles for both adolescent and adult trial participants Additional adolescent-related data from the PURPOSE 1 trial were also presented at CROI yesterday during an oral abstract session and press conference. PURPOSE 1 is the first adult Phase 3 HIV prevention trial to intentionally include adolescents aged 16 and 17 years, and trial enrollment was much higher than in typical adolescent-dedicated studies (124 adolescents, 56 of whom were assigned to the lenacapavir group). The data showed that observed lenacapavir plasma concentrations were comparable between adolescent and adult trial groups, with participants in both groups experiencing the same most common adverse events. There were zero incident HIV infections across the adolescent and adult groups receiving lenacapavir. Given these results, data submitted to regulatory authorities support the potential use of twice-yearly lenacapavir for adolescents who need or want PrEP The use of lenacapavir for the prevention of HIV is investigational and has not been determined to be safe or efficacious and is not approved anywhere globally. There is currently no cure for HIV or AIDS. About Lenacapavir Lenacapavir is approved in multiple countries for the treatment of adults with multi-drug resistant HIV in combination with other antiretrovirals. The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established. The multi-stage mechanism of action of lenacapavir is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, lenacapavir is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes. Lenacapavir is being evaluated as a long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program. Lenacapavir is being developed as a foundation for potential future HIV therapies with the goal of offering both long-acting oral and injectable options with several dosing frequencies, in combination or as a mono agent, that help address individual needs and preferences of people and communities affected by HIV. Science Magazine named lenacapavir its 2024 “Breakthrough of the Year.” About the PURPOSE Program Gilead’s landmark PURPOSE program is the most comprehensive and diverse HIV prevention trial program ever conducted. The program comprises five HIV prevention trials around the world that are focused on innovation in science, trial design, community engagement and health equity. The PURPOSE trials are evaluating the safety and efficacy of an investigational, twice-yearly injectable medicine, lenacapavir, to reduce the chance of getting HIV. The Phase 2 and 3 program, consisting of PURPOSE 1-5, is assessing the potential of lenacapavir to help a diverse range of people around the world who could benefit from PrEP. More information about the PURPOSE program, including individual trial descriptions, populations and locations, can be found at www.purposestudies.com . About Gilead HIV For more than 35 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 12 HIV medications , including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to help reduce new HIV infections, and the first long-acting injectable HIV treatment medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a treatable, preventable, chronic condition for millions of people. Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships , collaborations and charitable giving, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic for everyone, everywhere. Gilead was recognized as one of the leading philanthropic funders of HIV-related programs in a report released by Funders Concerned About AIDS. SOURCE: Gilead Sciences

Phase 3Clinical ResultPhase 1Phase 2Drug Approval

12 Mar 2025

·endpts.com

Researchers make case against Gilead in HIV product hopping fight

Can Gilead be held accountable for holding back the sale of an HIV drug it allegedly knew was safer than its blockbuster predecessor? That’s the question before the California Supreme Court, and the answer could offer a unique example of a situation where a pharma company can be liable for a product that isn’t defective. Two academics from the University of West Virginia and Dartmouth wrote in a JAMA Viewpoint on Wednesday that there’s a strong case to be made against Gilead because it knew that the later product was safer and deliberately delayed the launch of that drug. The original lawsuit, filed in San Francisco by 24,000 AIDS patients, similarly alleges that Gilead slow-walked the safer HIV drug, known as tenofovir alafenamide fumarate (TAF), to maximize profits from an older HIV drug, tenofovir disoproxil fumarate (TDF). The company delayed entry of TAF while knowing that TAF had fewer serious bone and kidney side effects, the plaintiffs said. A California appeals court ruled in January 2024 that delaying TAF may make Gilead liable for negligence. The court said that the “legal duty of a manufacturer to exercise reasonable care can … extend beyond the duty not to market a defective product” and that the plaintiffs should be able to present the evidence to a jury. Gilead appealed to the California Supreme Court, which agreed last May to review the case. The case has yet to be scheduled for arguments. The California high court’s question is: “Does a drug manufacturer have a duty of reasonable care to users of a drug it is currently selling, which is not alleged to be defective, when making decisions about the commercialization of an allegedly safer, and at least equally effective, alternative drug?” Many major biopharmas back Gilead in the case. JAMA co-author Sean Tu of West Virginia, whose research is partially funded by Arnold Ventures, told Endpoints News that the question “essentially amounts to whether pharma companies can delay the commercialization of drugs that could be safer than currently marketed products.” He said PhRMA and other pharma companies are wrong to tout this case as a “duty to innovate” case, meaning that if Gilead loses, manufacturers would have a legal obligation to develop and market improved, or safer, alternative drugs, even if the existing product isn’t defective. “Gilead had a safer product in the works, but decided not to release it because they were afraid it would ‘cannibalize’ profits from the older (TDF) product,” Tu said. “What resulted? Probably thousands of patient deaths and tens of thousands of adverse serious events. But it also resulted in hundreds of millions of added revenues for Gilead.” The twists and turns of the lawsuit against Gilead also highlight the difficulties in compensating patients who have been harmed by pharmaceuticals, according to the JAMA Viewpoint. They coin the term “drug versioning” to explain what Gilead did, which the authors call a new form of product hopping. “Drug versioning occurs when a manufacturer delays a newer version of an existing product to maximize profits from an older one,” they write. But they also note that Gilead would be liable only for withholding a product that was already developed and planned for commercialization, not for failing to invent a safer version in the first place. “Gilead’s liability is predicated on its proven knowledge of TAF’s benefits, not its mere possession of positive Phase 1 and 2 results,” the authors write.

Patent Infringement

100 Deals associated with Tenofovir Disoproxil Fumarate

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KEGG	Wiki	ATC	Drug Bank
D01982	-	J05AF07	DB00300

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Virus Diseases	China	Gilead Sciences, Inc.	18 Jun 2008
Hepatitis B	European Union	Gilead Sciences Ireland UC	04 Feb 2002
Hepatitis B	Iceland	Gilead Sciences Ireland UC	04 Feb 2002
Hepatitis B	Liechtenstein	Gilead Sciences Ireland UC	04 Feb 2002
Hepatitis B	Norway	Gilead Sciences Ireland UC	04 Feb 2002
Hepatitis B, Chronic	European Union	Gilead Sciences Ireland UC	04 Feb 2002
Hepatitis B, Chronic	Iceland	Gilead Sciences Ireland UC	04 Feb 2002
Hepatitis B, Chronic	Liechtenstein	Gilead Sciences Ireland UC	04 Feb 2002
Hepatitis B, Chronic	Norway	Gilead Sciences Ireland UC	04 Feb 2002
HIV Infections	United States	Gilead Sciences, Inc.	26 Oct 2001

Developing

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Indication	Highest Phase	Country/Location	Organization	Date
Pregnancy	Phase 3	Thailand	Gilead Sciences, Inc.	01 Jan 2013
Lymphoma	Phase 2	United States	GSK Plc	01 Dec 2015
Non-Hodgkin Lymphoma	Phase 2	United States	GSK Plc	01 Dec 2015
End Stage Liver Disease	Phase 2	United States	Gilead Sciences, Inc.	01 Apr 2006
End Stage Liver Disease	Phase 2	Canada	Gilead Sciences, Inc.	01 Apr 2006
End Stage Liver Disease	Phase 2	France	Gilead Sciences, Inc.	01 Apr 2006
End Stage Liver Disease	Phase 2	Germany	Gilead Sciences, Inc.	01 Apr 2006
End Stage Liver Disease	Phase 2	Greece	Gilead Sciences, Inc.	01 Apr 2006
End Stage Liver Disease	Phase 2	Italy	Gilead Sciences, Inc.	01 Apr 2006
End Stage Liver Disease	Phase 2	Poland	Gilead Sciences, Inc.	01 Apr 2006

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04202536 (Pubmed \| Clin Mol Hepatol)	Phase 4	Hepatitis B, Chronic hepatitis B virus (HBV) DNA	153	Besifovir 150 mg	bexlzgbuxc(yofmgovpfx) = ocxpyjjgoa ymahylmehu (xybcassqle )	Positive	17 Jan 2025
				Tenofovir Disoproxil Fumarate 300 mg	bexlzgbuxc(yofmgovpfx) = zwcmqsliul ymahylmehu (xybcassqle )
UEGW2024	Not Applicable	-	-	Tenofovir disoproxil fumarate (TDF)	kujfxpfssz(dzzcigvyub) = pnfppdzenm oruphyhjnp (fepvfoscmn ) View more	-	13 Oct 2024
				Tenofovir alafenamide (TAF)	kujfxpfssz(dzzcigvyub) = lfyfylsirh oruphyhjnp (fepvfoscmn ) View more
NCT03887702 (CTgov)	Phase 3	Hepatitis B \| Malignant Solid Neoplasm	4	Tenofovir Alafenamide+Tenofovir Disoproxil Fumarate+Entecavir (Arm 1 (TAF, TDF, Entecavir: Prophylactic))	acghddzshi(lngoffcure) = wrnhrsbrnr ktgwvmvckq (wuttkmtmtw, urfkqjdiyd - hmijdcefsh) View more	-	20 May 2024
				Tenofovir Alafenamide+Tenofovir Disoproxil Fumarate+Entecavir (Arm 2 (TAF, TDF, Entecavir: Upon Indication))	acghddzshi(lngoffcure) = ibnqqccpdg ktgwvmvckq (wuttkmtmtw, ttrkjdzcug - vgcetivzfz) View more
AASLD2023	Not Applicable	Decompensated cirrhosis of liver	3	REP 2139-Mg 250 mg	tufxarhwcx(sawroqdvib) = No significant adverse events (including ALT elevation) have been observed to date qnksqpxmeo (jepwtjjxlq )	-	10 Nov 2023
EASL2022	Not Applicable	Hepatitis B, Chronic	48	Tenofovir disoproxil fumarate (TDF)	vqlysvjauh(ptikpheeeu) = wcoblbxiup rbetrszpdp (udxxxnpftf )	Positive	25 Jun 2022
EASL2022	Not Applicable	Hepatitis B, Chronic First line	42	Tenofovir disoproxil fumarate (TDF)	joojhftoax(kzurzvftvi) = wnbinqidtx zmsttywkvw (pyjaeicriu )	-	25 Jun 2022
				Tenofovir alafenamide fumarate (TAF)	xwadryftyu(bhsebihpna) = zwueffsblt wjmnclfykm (lrbmwatwop )
EASL2022	Not Applicable	Hepatitis B HBV DNA \| ALP \| Z value for BMD	-	Tenofovir alafenamide fumarate (TAF)	rmgukfzmdg(jtdwkjxnpu) = mfdqannmos ksmrxlaaan (eojoktebhh )	-	23 Jun 2022
				Tenofovir disoproxil fumarate (TDF)	rmgukfzmdg(jtdwkjxnpu) = yfysxbcleo ksmrxlaaan (eojoktebhh )
NCT02224456 (CTgov)	Phase 4	Hepatitis B, Chronic \| Fibrosis \| Compensated cirrhosis	197	Tenofovir Disoproxil Fumarate	nhzqcjjnjw = jcvhnzrius apwwimzjit (rubygejnzp, asogflwwtx - vvofbcpncj) View more	-	14 Feb 2022
ANRS QUATUOR (IAS2022)	Not Applicable	HIV Infections	42	Intermittent doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF)	fhknhakkvu(xpmbmgehls) = oglvbeirel gosrrvwwsh (zhqcozutgl, 77.4 - 97.3) View more	Positive	01 Jan 2022

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