Bioequivalence study of two Tenofovir alafenamide fumarate 25mg tablet manufactured by tadbir kala jam company in comparison with Vemlidy (Gilead Sciences Company)

Start Date21 Nov 2024

Sponsor / Collaborator-

NCT05652478 / RecruitingPhase 2IIT

A Phase 2 Randomized Cross-Over Design Study of the Early Metabolic Effects of Dolutegravir or Tenofovir Alafenamide in Healthy Volunteers

Background:
People with HIV take drugs to keep the amount of virus in their body low. One type of these drugs, called integrase strand transfer inhibitors (INSTIs), can cause weight gain over time. Weight gain can cause diabetes, heart disease, and other serious issues. Researchers want to understand how INSTIs cause weight changes.
Objective:
To see how a common INSTI, dolutegravir (DTG), affects how the body uses energy. DTG will be compared with a non-INSTI drug, tenofovir alafenamide (TAF).
Eligibility:
Healthy people aged 18 to 55.
Design:
Participants will be screened. They will have a physical exam and blood tests. They will have a nutritional assessment and tests of their heart function.
Participants will have 2 inpatient stays at the clinic. Each stay will be for 11 nights, with a 3-week break between.
Both DTG and TAF are gel caps swallowed once per day by mouth. Participants will take 1 drug for 8 days during each stay.
Participants will have tests to see how their body uses energy:
They will spend 23 continuous hours in a special room that measures how much oxygen they breathe in and how much carbon dioxide they breathe out. They will do this a total of 6 times.
They will have a DEXA (dual-energy X-ray absorptiometry). DEXA is a kind of X-ray that measures body fat and bone density.
They will lie on a table. Electrodes will be placed on their hands and feet to measure body fat and lean body mass.
They will stand still on a platform for about 30 seconds. High-resolution laser cameras will scan their bodies.

Start Date05 Nov 2024

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

IRCT20220211053992N41 / RecruitingIIT

In vivo fasted-state bioequivalence study of Tenofovir Alafenamide 25 mg tablet manufactured by Exir Pharmaceutical Co. compared to innovator product

Start Date06 Oct 2024

Sponsor / Collaborator

Tabriz University of Medical Sciences

100 Clinical Results associated with Tenofovir Alafenamide Fumarate

100 Translational Medicine associated with Tenofovir Alafenamide Fumarate

100 Patents (Medical) associated with Tenofovir Alafenamide Fumarate

1,496

Literatures (Medical) associated with Tenofovir Alafenamide Fumarate

01 Feb 2025·JOURNAL OF COLLOID AND INTERFACE SCIENCE

Surface coating engineering of titanate anodes based on tannic acid-formaldehyde polymer chelating bismuth ions for advanced sodium-ion capacitors

Article

Author: Xiao, Yingjie ; Yue, Gentian ; Guo, Shouwu ; Huo, Jinghao ; Zhang, Lifeng

As a battery-type anode material for sodium ion capacitors (SICs), titanate (H₂Ti₂O₅·H₂O, HTO) exhibits good rate capability due to its layered structure, easy to insert Na⁺ ions and low potential during sodium-ion storage. However, the structure is unstable due to the lattice distortion resulting from the irreversible embedment of Na⁺ in the process of sodium storage. So there is a significant mismatch between the dynamic reaction of the HTO anode and the capacitive cathode. Surface coating engineering is a useful strategy for stabilizing the HTO structure, which is critical for improving the kinetic response. In this work, a surface coating technique is designed to enhance the surface of HTO nanoarrays on titanium foil by using the oligomers of tannic acid formaldehyde polymer (TAF) chelated Bi³⁺ ions (Bi-TAF). As a binder-free anode, HTO coated with Bi-TAF (HTO@Bi-TAF) exhibits more excellent capacity (335.2 mA h g^-1, 0.1 A g^-1), rate capability (212.3 mA h g^-1, 2.0 A g^-1), and cycle stability (97 % capacity maintenance following 2000 cycles at 1.0 A g^-1) than HTO and HTO coated with TAF (HTO@TAF). At the sweep rate of 1.0 mV s^-1, the kinetic investigation reveals that the capacitance contribution of HTO@Bi-TAF is 86 %. The SICs exhibit a significant energy/power density (89.4 Wh kg^-1/250 W kg^-1). This work shows that the Bi-TAF polymer coating has a dual effect of rate capability improvement and structural protection on the prepared HTO. This results in a reasonable and effective surface coating strategy that provides outstanding rate capability and extended cycle performance of titanium-based anode materials for SICs.

31 Dec 2024·HIV Research & Clinical Practice

A randomised control trial of BIC/F/TAF vs DRV/c/F/TAF in context of HIV test-and-treat, BicTnT

Article

Author: Kang, Sujin ; Henderson, Merle ; Soler-Carracedo, Alfredo ; Clarke, Amanda ; Xhikola, Arnold ; Whitlock, Gary ; Fidler, Sarah ; Boffito, Marta ; Khawaja, Akif ; Adams, Tanya ; Jahan, Ishrat ; Milinkovic, Ana ; Taylor, Graham

BACKGROUND:

Head-to-head data for bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF; B) and darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/F/TAF; D) are lacking in the context of rapid antiretroviral therapy (ART) initiation. This study, BIC-T&T, evaluates the efficacy and tolerability of B vs D in a UK test-and-treat setting.

SETTING:

BIC-T&T was a randomised, open-label, multi-centre, study in which participants initiated ART within 14 days after confirmed HIV-1 diagnosis before baseline laboratory.

METHODS:

The primary endpoint is the virological response (HIV RNA < 50copies/mL) at week 12 by time-weighted average change in log₁₀ HIV RNA recorded in viral load assays from treatment initiation to week 12, using two-sample Wilcoxon rank-sum test.

RESULTS:

36 participants were randomised: 94% were male, 53% white; mean (SD) age was 35 years (11.8). Baseline mean (±SD) log₁₀ HIV-RNA was 4.79 (± 0.87) log₁₀ copies/mL and CD4 505 (±253) cells/mm³. The mean (±SD) time from confirmed HIV diagnosis to ART initiation was 7.9 (± 3.7) days. The time-weighted mean decrease in log₁₀ HIV RNA from treatment initiation to week 12 was significantly greater in B in comparison to D (3.1 vs. 2.6 log₁₀ copies/mL, p < 0.001). Both regimens demonstrated good tolerability with infrequent laboratory abnormalities and no grade 3 or 4 adverse events.

CONCLUSION:

In this first head-to-head study in the context of ART initiation, HIV RNA decline from baseline to week 12 was significantly more rapid for BIC/F/TAF compared with DRV/c/F/TAF.

01 Dec 2024·HIV Research & Clinical Practice

Impact of switching to injectables cabotegravir and rilpivirine on sleep disturbances in a cohort of people living with HIV.

Article

Author: Sasset, Lolita ; Agostini, Elena ; Gardin, Samuele ; Presa, Nicolò ; Mazzitelli, Maria ; Leoni, Davide ; Scaglione, Vincenzo ; Vania, Eleonora ; Cattelan, Annamaria

BACKGROUND:

Recently, injectable cabotegravir/rilpivirine (ICAB/RPV) became available for HIV treatment. However, there are no real-life data on the impact of switching to ICAB/RPV on sleep disturbances (SD). Therefore, we aimed at assessing and investigating this aspect in our cohort.

METHODS:

A SD multidimensional assessment (Epworth Sleepiness scale, Insomnia severity Index, Berlin Questionnaire, and Pittsburg Sleep Quality Index, PSQI) was performed to all people who consented before starting ICAB/RPV and 12 wk after the switch. Demographics, life-style habits, laboratory, and clinical data were collected from medical health records.

RESULTS:

To June 2023, 46 people were included, 76.1% males, with a median age of 48.5 (IQR: 41-57), 50% had multimorbidity, 13% was on polypharmacy. Median age with HIV and CD4 + T cell count nadir were 10 (5-19.5) years and 360 (205-500) cell/mm³, respectively. The reason to start a long-acting strategy was person's choice in all cases. Baseline antiretroviral regimens were mostly: tenofovir alafenamide/emtricitabine/rilpivirine (39.1%) and dolutegravir/lamivudine (32.6%). No significant changes were observed in any of the scores for each questionnaire, but for a worsening PSQI. 37% people reported a subjectively improved sleep quality, even if statistically significant changes were not observed in almost all the sleep parameters.

CONCLUSIONS:

To the best of our knowledge, this is the first study exploring impact of switching to ICAB/RPV on SD. Despite integrase inhibitor have been associated with SD, we did not observed a negative impact on sleep quality after the switch to ICAB/RPV. More studies and with larger number of people are necessary to confirm our results.

News (Medical) associated with Tenofovir Alafenamide Fumarate

22 Oct 2024

·www.biospace.com

Gilead to Present Latest Research Across Key Liver Disease Indication at the American Association for the Study of Liver Disease (AASLD) Meeting 2024

- Key Insights from Viral Hepatitis, PBC, and MASH/Fibrosis Studies Highlight Gilead’s Ongoing Commitment to Advancing Life-Changing Liver Disease Research - FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq: GILD) today announced new research to be presented at The Liver Meeting ® 2024, hosted by the American Association for the Study of Liver Diseases (AASLD) from November 15-19 in San Diego, Calif. More than 40 abstracts will be presented with key data, including 11 abstracts reporting new data on primary biliary cholangitis (PBC). The data will include findings from the RESPONSE trial that demonstrate the efficacy and safety pro Livdelzi ® (seladelpar) in people living with PBC and compensated cirrhosis. Additionally, data will be presented on the effects of Livdelzi on pruritus (chronic itching), a symptom that has significant impact on the quality of life of people living with PBC, along with interim long-term efficacy and safety results from the ongoing ASSURE study. Beyond PBC, Gilead will be presenting an interim analysis of the Phase 3 MYR301 study, which is evaluating people living with hepatitis Delta virus (HDV) who received bulevirtide monotherapy (2 mg for 144 weeks; 10 mg for 144 weeks; or 10 mg for 96 weeks) for chronic HDV and have been off treatment for 48 weeks. The study is evaluating whether or not patients treated with bulevirtide monotherapy for 2-3 years maintained virological and biochemical responses one year after stopping treatment. An additional 144-week analysis of patient-reported outcomes for individuals treated with bulevirtide 2 mg will also be presented, adding to the wealth of long-term data for the treatment for chronic HDV. “We’re excited to share our latest research at The Liver Meeting, as we push the boundaries of what’s possible in liver disease treatment. The breadth of this research reflects Gilead’s unwavering dedication to advancing life-changing science and shaping healthier futures for people living with liver disease,” said Anu Osinusi, Vice President of Clinical Development for Hepatitis, Respiratory and Emerging Viruses, Gilead Sciences. “The depth and range of our data, spanning both viral and inflammatory liver diseases, underscores our commitment to making a meaningful impact at every stage of a person’s journey in liver disease. Our goals go far beyond treatment alone—our work spans awareness, education, screening, diagnosis, and long-term care, all intending to address unmet needs and enhance treatment outcomes.” Gilead will also present hepatitis C virus (HCV) data which will include safety and tolerability outcomes for Epclusa ® (velpatasvir/sofosbuvir) in pregnant individuals with chronic HCV (the STORC study). As a special population that is often excluded from clinical research, these results may help clinicians better support pregnant people living with HCV, which in turn may reduce the risk of transmission to infants. Furthermore, real-world findings from the SVR10K study on HCV will be showcased, demonstrating the effects of direct-acting antivirals against all HCV genotypes across diverse regions. Late-breaking data from a Phase 2a open-label study assessing the safety and efficacy of novel combination therapies for chronic hepatitis B virus (HBV) will also be presented by Gilead. Key Abstracts at AASLD 2024: ID Abstract Title PBC 164 Efficacy and Safety of Seladelpar in Patients with PBC and Compensated Cirrhosis in the Phase 3 Placebo-controlled RESPONSE Trial 167 Attenuation, Near Resolution, and Prevention of Pruritis in Patients with PBC Treated with Seladelpar: A Secondary Analysis of Patterns of Pruritis Change in the RESPONSE Trial 4339 Alkaline Phosphatase Changes with Seladelpar Across Subgroups of Primary Biliary Cholangitis Patients in the RESPONSE Trial 4342 Seladelpar and Reductions in Lipids in Patients with Primary Biliary Cholangitis with and without Statin use in the Phase 3 Placebo-controlled RESPONSE Study 4341 Long-term Safety of Seladelpar 10 mg with up to 5 Years of Treatment in Patients with Primary Biliary Cholangitis Primary sclerosing cholangitis (PSC) 151 Associations Between Biomarkers and Magnetic Resonance Imaging-derived ANALI Score in Patients with Primary Sclerosing Cholangitis: Analysis from the Phase 3 PRIMIS Study HDV 1147 Efficacy and Safety of BLV Monotherapy for Chronic Hepatitis Delta: Post Treatment Results through 48 Weeks after the End of Treatment from an Interim Analysis of a Randomized Phase 3 Study MYR301 1193 Patient-reported Outcomes among Patients with Chronic Hepatitis Delta Treated with Bulevirtide 2 mg: A Long-term Analysis of the Phase 3 MYR301 Trial at 144 Weeks 139 Long-term Bulevirtide Monotherapy in Patients with HDV-related Compensated Cirrhosis: Effectiveness, Safety and Clinical Outcomes from the Retrospective Multicenter European Study (SAVE-D) HCV 222 Safety, Tolerability, and Outcomes of Velpatasvir/Sofosbuvir in Treatment of Chronic Hepatitis C Virus during Pregnancy (STORC) 1455 The SVR10K Study: A Real-world Data with Pangenotypic Direct-acting Antivirals across Multiple Diverse Regions 1476 Hepatitis C Treatment Uptake Differs by Gender among a Commercially Insured Population in the United States HBV 1380 Results from a Phase 2a, Open-label Study to Evaluate the Safety and Efficacy of Novel Combination Therapies Containing VIR-2218, Selgantolimod, and Nivolumab for the Treatment of Chronic Hepatitis B 1252 Effectiveness and Safety of Tenofovir Alafenamide in Chronic Hepatitis B Patients with Suboptimal Response to Antiviral Therapy 1337 Characterization of Changes in Noninvasive Fibrosis Markers over 8 Years of Tenofovir-based Treatment in Chronic Hepatitis B Patients Enrolled in Two Phase 3 Trials Nonalcoholic steatohepatitis (NASH)/Fibrosis 1520 Prospective Validation of the Mediterranean Diet Adherence Screener (MEDAS) for Point-of-care Assessment of Diet Quality in Patients with Metabolic Dysfunction-associated Steatotic Liver Disease For more information, including a complete list of abstract titles being presented at the meeting, please visit the AASLD website . In July 2023, the European Commission (EC) granted full Marketing Authorization (MA) for bulevirtide 2 mg for the treatment of adults with chronic HDV and compensated liver disease. Bulevirtide’s conditional MA license in Great Britain was converted to a full MA in August 2023 and a full MA was granted in Switzerland and Australia in 2024. In regions where it is not approved, including the U.S., bulevirtide 2 mg is an investigational product. In these regions, health authorities have not established the safety and efficacy of bulevirtide. Bulevirtide 10 mg is an investigational product and has not been approved anywhere. Cilofexor and selgantolimod are investigational compounds and are not approved by the FDA or any other regulatory authority; their safety and efficacy have not been established. Please see below for the U.S. Indications and Important Safety Information, including BOXED WARNINGS, for Epclusa and Livdelzi. U.S. Important Safety Information And Indication for EPCLUSA BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. Contraindications If EPCLUSA is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information. Warnings and Precautions Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with EPCLUSA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia. Risk of Reduced Therapeutic Effect Due to Use with P-gp Inducers and/or Moderate to Strong Inducers of CYP2B6, CYP2C8 or CYP3A4 : Rifampin, St. John’s wort and carbamazepine are not recommended for use with EPCLUSA as they may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations. Adverse Reactions The most common adverse reactions (≥10%, all grades) with EPCLUSA in adults and pediatric patients 6 years of age and older were headache and fatigue; and when used with RBV in adults with decompensated cirrhosis were fatigue, anemia, nausea, headache, insomnia and diarrhea. The most common adverse reactions (≥10%, grade 1 or 2) in pediatric patients less than 6 years of age were vomiting and spitting up the drug. Drug Interactions Coadministration of EPCLUSA is not recommended with topotecan due to increased concentrations of topotecan. Coadministration of EPCLUSA is not recommended with proton-pump inhibitors, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir. Consult the full Prescribing Information for EPCLUSA for more information on potentially significant drug interactions, including clinical comments. Indication EPCLUSA is indicated for the treatment of adult and pediatric patients 3 years of age and older with chronic hepatitis C virus genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis. U.S. Important Safety Information for LIVDELZI Warnings and Precautions Fractures: Fractures occurred in 4% of LIVDELZI-treated patients compared to no placebo-treated patients. Consider the risk of fracture in the care of patients treated with LIVDELZI and monitor bone health according to current standards of care. Liver Test Abnormalities: LIVDELZI has been associated with dose-related increases in serum transaminase (AST and ALT) levels > 3 x ULN in patients receiving 50 mg and 200 mg once daily (5x and 20x higher than the recommended dosage of 10 mg once daily). Perform baseline clinical and laboratory testing when starting LIVDELZI and monitor thereafter according to routine patient management. Interrupt treatment if the liver tests (ALT, AST, total bilirubin, and/or ALP) worsen, or if the patient develops signs and symptoms of clinical hepatitis (eg, jaundice, right upper quadrant pain, eosinophilia). Consider permanent discontinuation if liver tests worsen after restarting LIVDELZI. Biliary Obstruction: Avoid use of LIVDELZI in patients with complete biliary obstruction. If biliary obstruction is suspected, interrupt LIVDELZI and treat as clinically indicated. Adverse Reactions The most common adverse reactions (≥5%) with LIVDELZI were headache (8%), abdominal pain (7%), nausea (6%), abdominal distension (6%), and dizziness (5%). Drug Interactions OAT3 Inhibitors and Strong CYP2C9 Inhibitors: Avoid coadministration with LIVDELZI due to increased LIVDELZI exposure. Rifampin: Monitor biochemical response (e.g., ALP and bilirubin) when patients initiate rifampin during LIVDELZI treatment. Coadministration may result in delayed or suboptimal biochemical response of LIVDELZI. Dual Moderate CYP2C9 and Moderate-to-Strong CYP3A4 Inhibitors and BCRP Inhibitors (eg, cyclosporine): Monitor closely for adverse effects. Concomitant administration with LIVDELZI may increase LIVDELZI exposure. CYP2C9 Poor Metabolizers Using Moderate-to-Strong CYP3A4 Inhibitors: Monitor more frequently for adverse reactions as concomitant use of a moderate-to-strong CYP3A4 inhibitor in patients who are CYP2C9 poor metabolizers may increase LIVDELZI exposure and risk of LIVDELZI adverse reactions. Bile Acid Sequestrants: Administer LIVDELZI at least 4 hours before or 4 hours after taking a bile acid sequestrant, or at as great an interval as possible. Pregnancy and Lactation Pregnancy: There are insufficient data from human pregnancies exposed to LIVDELZI to allow an assessment of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Report pregnancies to Gilead Sciences, Inc., at 1-800-445-3235. Lactation: There are no data on the presence of LIVDELZI in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LIVDELZI and any potential adverse effects on the breastfed infant from LIVDELZI. Indication LIVDELZI is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. This indication is approved under accelerated approval based on a reduction of ALP. Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Limitations of Use: Use of Livdelzi is not recommended in patients who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy). About HDV HDV is considered the most aggressive or severe form of viral hepatitis, associated with more rapid progression towards liver-related death and liver cancer in people with HBV. On average, HDV progresses to cirrhosis within 5 years and to liver cancer within 10 years. Nearly 5% of people who have a chronic infection with HBV are estimated to have HDV, equating to 12-15 million people worldwide. The prevalence of HDV infection is largely underestimated due to lack of universal testing of HBV-positive individuals for HDV. About PBC PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the U.S.). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of alkaline phosphatase (ALP), alanine transaminase (ALT) and gamma-glutamyl transferase (GGT), enzymes found primarily in the liver, as well as total bilirubin. The most common symptoms of PBC are pruritus and fatigue, which can be debilitating for some people. Progression of PBC is associated with an increased risk of liver-related mortality. About Gilead Sciences in Liver Disease For decades, Gilead has pioneered the way forward to improve the lives of people living with liver disease around the world. We have helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For people living with hepatitis B or D, our focus on advancing our medicines drives hope that today’s research will turn into tomorrow’s cures. Beyond viral hepatitis, we’re working to deliver advanced treatments for people living with PBC. But our commitment doesn’t stop there. Through our ground-breaking science and collaborative partnerships, we strive to create healthier futures for everyone living with liver disease. We are committed to a future without liver disease. About Gilead Sciences 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, cancer and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials or studies, including those involving Epclusa, Hepcludex (bulevirtide), Livdelzi (seladelpar), cilofexor and selgantolimod (such as the ASSURE, RESPONSE, MYR301, STORC and SVR10K studies); uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the FDA and other regulatory authorities may not approve bulevirtide for the treatment of HDV, and the risk that any such approvals, if granted, may be subject to significant limitations on use or subject to withdrawal or other adverse actions by the applicable regulatory authority; the possibility that Gilead may make a strategic decision to discontinue development of investigational programs for indications that are currently under evaluation and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. Epclusa, Hepcludex, Livdelzi, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. For more information about Gilead, please visit the company’s website at , follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000. Contacts Meaghan Smith, Media public_affairs@gilead.com Jacquie Ross, Investors investor_relations@gilead.com

Phase 2Clinical ResultDrug ApprovalPhase 3

22 Oct 2024

·www.pharmaceutical-technology.com

Gilead and MSD to advance once-weekly HIV treatment to Phase III

The treatment combines MSD’s islatravir with Gilead’s lenacapavir. Credit: Ground Picture via Shutterstock. Gilead Sciences and MSD are advancing their once-weekly HIV treatment regimen to Phase II trials, following promising results from a 48-week study. The treatment combines MSD’s islatravir, an experimental nucleoside reverse transcriptase inhibitor, with Gilead’s lenacapavir, marketed as Sunlenca for use in combination with other antiretroviral drugs to treat people with multidrug-resistant HIV infection. In contrast to currently available daily HIV medications, such as Gilead’s Biktarvy (bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg), this new option could offer a long-acting alternative for people living with HIV. In the Phase II trial (NCT05052996), 104 virologically suppressed adults on Biktarvy were randomly assigned to either continue their daily regimen or switch to the once-weekly islatravir/lenacapavir combination. At the 24-week mark, 94.2% of patients on the experimental treatment maintained viral loads below 50 copies m/L – a key threshold for HIV suppression – matching the Biktarvy group. By week 48, the new regimen continued to demonstrate non-inferior efficacy, with 94.2% of participants achieving sustained viral suppression, compared to 92.4% of those who remained on Biktarvy. These results suggest that the once-weekly combination could provide a more convenient option for patients, potentially reducing the burden of daily medication. Currently, the only long-acting HIV treatment available in the US is Viiv Healthcare’s Cabenuva, which is administered as a monthly or bi-monthly injection. This could make Gilead and MSD’s new pill an attractive alternative to those seeking a less frequent oral regimen. See Also: Editas and Genevant team up to develop gene editing therapies World Osteoporosis Day calls for urgent action to prevent fragility fractures Biktarvy is approved as a once-daily pill to treat patients living with certain types of HIV. The drug generated $11.9bn in global sales in 2023, as per Gilead’s financials. According to GlobalData’s Pharma Intelligence Center, Biktarvy will generate $15.3bn in sales in 2030. GlobalData is the parent company of Pharmaceutical Technology. In the announcement accompanying the results, Elizabeth Rhee, vice president of global clinical development of Merck Research Laboratories said: “Daily single-tablet regimens have helped to transform HIV care but can be challenging for some people to maintain. Novel HIV treatment options that allow for less frequent oral dosing have the potential to help support adherence, and address stigma faced by some individuals taking daily oral therapy.” MSD previously tried to develop a higher dose of islatravir, however it had to pause development after it led to a drop in counts of lymphocytes and CD4+ T cells in clinical trials in 2021. In MSD and Gilead’s Phase II study, there were no differences in immune cell count changes between the Biktarvy and experimental groups. Additionally, no participants discontinued because of a decrease in CD4+ T-cell or lymphocyte counts. Encouraged by these results, Gilead and MSD are now advancing the treatment in Phase III trials. Gilead is also advancing lenacapavir as a PrEP medication, a group of drugs that HIV-negative people can take to minimise the risk of contracting HIV. The company plans to use the data from two Phase III clinical trials – PURPOSE-1 (NCT04994509) and PURPOSE-2 (NCT04925752) – to support a series of global regulatory filings for lenacapavir for PrEP that will begin by the end of 2024.

Phase 2Phase 3Clinical ResultDrug Approval

21 Oct 2024

·pipelinereview.com

Gilead and Merck Announce Phase 2 Data Showing a Treatment Switch to an Investigational Oral Once-Weekly Combination Regimen of Islatravir and Lenacapavir Maintained Viral Suppression in Adults at Week 48

– Novel Investigational Combination Regimen is Advancing to Phase 3 and has the Potential to Become the First Weekly Oral HIV Treatment – FOSTER CITY, CA, & RAHWAY, NJ, USA I October 19, 2024 I Gilead Sciences, Inc. (Nasdaq: GILD) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced new results from a Phase 2 clinical study evaluating the investigational combination of islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, and lenacapavir, a first-in-class HIV-1 capsid inhibitor. These late-breaking data were presented during an oral session at ID Week 2024 , taking place in Los Angeles, and virtually, from October 16-19. At 48 weeks, the novel investigational combination maintained a high rate (n=49; 94.2%) of viral suppression (HIV-1 RNA <50 copies/mL) in virologically suppressed adults, a secondary endpoint of the study. Zero participants had a viral load of ≥50 copies/mL at Week 48. Week 24 results, including the study’s primary endpoint, were previously presented at the 31st Conference on Retroviruses and Opportunistic Infections (CROI). “The future of HIV treatment is person-centered, with long-acting options tailored to help meet the needs and preferences of people affected by HIV,” said Jared Baeten, MD, PhD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “There is no ‘one size fits all’ approach. The complexities of HIV care require putting people first in the development of biomedical innovations as we keep striving to offer options for all those living with HIV. These data presented at IDWeek demonstrate our commitment to continuous scientific discovery aimed at further transforming the HIV treatment landscape.” In this open-label, active-controlled study ( NCT05052996 ), virologically suppressed adults (n=104) on Biktarvy ® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) were randomly allocated in a 1:1 ratio to receive either oral islatravir 2 mg and lenacapavir 300 mg once a week (n=52) or to continue daily oral Biktarvy (n=52). The median age of participants was 40 years (20-76). Eighteen percent of participants were assigned female at birth, 50% were non-white, and 29% were Latine. The proportion of individuals with HIV-1 RNA <50 c/mL at Week 48 by FDA snapshot algorithm (a secondary endpoint), showed that participants who switched to treatment with once-weekly islatravir and lenacapavir (ISL + LEN) or continued Biktarvy maintained comparable high rates of HIV suppression at Week 48 (94.2% v. 92.3%, respectively). No participants treated with either ISL + LEN or Biktarvy had a viral load of ≥ 50 copies/mL at Week 48 (another secondary endpoint). Treatment-related-adverse events (TRAEs), as attributed by study investigator, were experienced by 19.2% of participants (n=10/52) in the ISL + LEN group and the most common were dry mouth (n=2/52; 3.8%) and nausea (n=2/52; 3.8%). TRAEs were reported by 5.8% of participants in the Biktarvy group (n=3/52). No grade 3 or 4 TRAEs related to the study drug were reported in either treatment group. Two participants (n=2/52; 3.8%) discontinued ISL + LEN due to adverse events unrelated to the drug. At Week 48 no significant differences were seen between treatment groups in mean change from baseline in CD4+ T-cell counts or absolute lymphocyte counts. No participants discontinued due to a decrease in CD4+ T-cell or lymphocyte counts. “Daily single-tablet regimens have helped to transform HIV care but can be challenging for some people to maintain. Novel HIV treatment options that allow for less frequent oral dosing have the potential to help support adherence, and address stigma faced by some individuals taking daily oral therapy,” said Dr. Elizabeth Rhee, Vice President, Global Clinical Development, Merck Research Laboratories. “We are pleased to see these encouraging 48-week data for this once-weekly oral combination regimen and advance to phase 3 clinical trials in collaboration with Gilead.” Along with these most recent study results, the potent antiviral activities, and pharmacokinetic profiles of islatravir and lenacapavir support their continued development as an investigational once-weekly oral combination regimen for use in people with HIV who are virologically suppressed. This investigational combination of weekly oral ISL 2 mg + LEN 300 mg is being further evaluated as a fixed-dose combination regimen in two Phase 3 studies ( NCT06630286 and NCT06630299 ) in virologically suppressed people with HIV. Islatravir in combination with lenacapavir is investigational and not approved anywhere globally. The safety and efficacy of the combination of islatravir and lenacapavir have not been established. Lenacapavir is being studied in multiple ongoing early and late-stage development programs and has the potential to offer a diverse set of person-centric options for treatment that could uniquely fit into the lives of people with HIV. The use of lenacapavir for HIV treatment in virologically suppressed individuals is investigational and not approved anywhere globally. Please see below for the U.S. Indication and Important Safety Information, including Boxed Warning , for Biktarvy. There is currently no cure for HIV or AIDS. About Islatravir (MK-8591) and Merck’s HIV Research Islatravir (MK-8591) is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) under evaluation in multiple ongoing early and late-stage clinical studies in combination with other antiretrovirals for the treatment of HIV-1. Studies with islatravir are designed to offer different dosing options as potential daily and once-weekly treatments. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here . About Lenacapavir 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. Lenacapavir is being evaluated as a potential long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program. The goal is to offer both long-acting oral and injectable options with various dosing frequencies in combination with other antiretroviral agents for treatment or as a single agent for prevention. This approach aims to help address the individual needs and preferences of people with HIV and people who could benefit from pre-exposure prophylaxis (PrEP). The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use has not been established. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter) , Facebook , Instagram , YouTube and LinkedIn . Merck’s Commitment to HIV For more than 35 years, Merck has been committed to scientific research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has been pioneering in the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV, with the goal of reducing the growing burden of infection worldwide. We want to ensure people are not defined by HIV and our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives aimed at the goal of helping to end the HIV epidemic for everyone. About Gilead Sciences 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, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. About Gilead Sciences in HIV For 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 is recognized as one of the leading funders of HIV-related programs in a report released by Funders Concerned About AIDS. U.S. full Prescribing Information for Biktarvy, including BOXED WARNING , is available at www.gilead.com . SOURCE: Gilead Sciences

Clinical ResultPhase 3Phase 2

100 Deals associated with Tenofovir Alafenamide Fumarate

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KEGG	Wiki	ATC	Drug Bank
D10605	Tenofovir Alafenamide Fumarate	J05AF13	DB09299

R&D Status

Approved

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Indication	Country/Location	Organization	Date
Virus Diseases	CN	Gilead Sciences Ireland UC	09 May 2019
Hepatitis B, Chronic	US	Gilead Sciences, Inc.	10 Nov 2016
Liver Diseases	US	Gilead Sciences, Inc.	10 Nov 2016
HIV Infections	CA	Gilead Sciences Canada, Inc.	-

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Indication	Highest Phase	Country/Location	Organization	Date
Fatigue	Phase 2	US	Gilead Sciences, Inc.	15 Sep 2022
Multiple Sclerosis, Relapsing-Remitting	Phase 2	US	Gilead Sciences, Inc.	15 Sep 2022
Hepatitis B	Phase 1	US	Gilead Sciences, Inc.	22 Dec 2014
Hepatitis B	Phase 1	DE	Gilead Sciences, Inc.	22 Dec 2014
Hepatitis B	Phase 1	NZ	Gilead Sciences, Inc.	22 Dec 2014

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04850950 (Pubmed \| Am J Gastroenterol)	Phase 4	Hepatitis B HBV DNA	239	Expected Eight-Week Prenatal Tenofovir Alafenamide Prophylaxis	qxgupjhxxy(ywqpkplhvw) = uxlpjmdwkd lsigkmlbfi (pppsuibbhv, 4.5% - 11.1) View more	Positive	09 Oct 2024
				Expected Twelve-Week Perinatal Tenofovir Alafenamide Prophylaxis	irxcawriwk(iknlruvlzf) = csdbhckaly vyvwdqxsxh (elnkskbylz )
NCT04937881 (PrEP-PP PK, CTgov)	Phase 3	HIV Infections	39	Tenofovir Alafenamide (TAF Arm)	qrkodxgixl(ofxfynufhg) = baeqdnkwuu stpsbugoao (wosrjbzyfg, jszrvncwtf - fdjshkmsze) View more	-	03 Sep 2024
				Tenofovir Disoproxil Fumarate (TDF Arm)	qrkodxgixl(ofxfynufhg) = dmycoiwmaf stpsbugoao (wosrjbzyfg, vievbfmztk - osyfepfqor) View more
NCT03180619 (Pubmed)	Phase 2	-	124	Tenofovir alafenamide 25 mg	vfxlevcxgl(ogeodizith) = occurred in 20 (22%) part A participants and in ten (32%) part B participants; none were related to treatment umrxpdxpfr (dxyvssqyio ) View more	Positive	01 Aug 2024
NCT03695029 (Pubmed) Manual	Phase 4	Hepatitis B	131	Tenofovir alafenamide	cmlejvvfxg(snoejfheay) = qwhahuoqez sktxqfawmq (ohutzbamua ) View more	Positive	01 Jun 2024
				Tenofovir disoproxil fumarate	cmlejvvfxg(snoejfheay) = poaezeahma sktxqfawmq (ohutzbamua ) View more
NCT03887702 (CTgov)	Phase 3	Hepatitis B \| Malignant Solid Neoplasm	4	Tenofovir Alafenamide+Tenofovir Disoproxil Fumarate+Entecavir (Arm 1 (TAF, TDF, Entecavir: Prophylactic))	hhkldmyahf(ndxqenopkn) = rucavjljxv zexnsqtzdu (udpghppizh, ciahyjnsmf - twandawher) View more	-	20 May 2024
				Tenofovir Alafenamide+Tenofovir Disoproxil Fumarate+Entecavir (Arm 2 (TAF, TDF, Entecavir: Upon Indication))	hhkldmyahf(ndxqenopkn) = cedhclshpn zexnsqtzdu (udpghppizh, kqhaljvinq - rrycnqgofx) View more
Rainbow study (Pubmed \| Int J Antimicrob Agents)	Phase 4	HIV Infections HIV-RNA	30	BIC/FTC/TAF	rgozavidsv(duydqrhzba) = Two participants developed IRIS wrehjefrjp (aaubwqfjdi ) View more	Positive	01 Jan 2024
Pubmed	Not Applicable	Hepatitis B, Chronic	270	Tenofovir alafenamide	ujomlvrcgw(fiwskxxrjd) = kqxzqekcri ydzqgnwjvs (maguxswmge ) View more	Positive	01 Jan 2024
				Nucleos(t)ide analogues	ujomlvrcgw(fiwskxxrjd) = rpdojlbnzq ydzqgnwjvs (maguxswmge ) View more
NCT03752658 (AASLD2023)	Not Applicable	Hepatitis B, Chronic	500	Tenofovir alafenamide (TAF) monotherapy	juhaqotmmi(luewzsgsqe) = zgblhqdufz xfxdpyffde (pfnavukefl ) View more	-	10 Nov 2023
				Tenofovir alafenamide (TAF) plus entecavir (ETV)	juhaqotmmi(luewzsgsqe) = cwkanbtvgs xfxdpyffde (pfnavukefl ) View more
AASLD2023	Not Applicable	Hepatitis B, Chronic HBeAg-positive \| HBeAg-negative	1,298	Tenofovir alafenamide (TAF)	atajhyhmpz(mrowkxewvo) = sebbuverel tswhkuwgpe (ajsvckczes )	-	10 Nov 2023
AASLD2023	Not Applicable	Hepatitis B, Chronic \| Decompensated cirrhosis of liver	182	Tenofovir alafenamide (TAF)	ycwlkytvmy(ztadhosimp) = fgxewfivzj dlcqisfnrb (xfkxvdpkil ) View more	-	10 Nov 2023

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