Hepatomegaly

STOCKHOLM, Oct. 30, 2024 /PRNewswire/ -- Sobi® (STO: SOBI) today announced that new research showing the effect of emapalumab in patients with macrophage activation syndrome (MAS) in Still's disease, including systemic juvenile idiopathic arthritis (sJIA) and adult-onset still's disease (AOSD) who had an inadequate response to high-dose glucocorticoids (GCs) will be presented at the American College of Rheumatology (ACR) Convergence in Washington D.C. The data were pooled from two open-label, single-arm interventional studies, the phase 3 NI-0501-14 study [EMERALD; NCT05001737] and NI-0501-06 [NCT03311854], including 39 patients with MAS. Key results: Complete response at week 8: At week 8, 21 patients (53.8%) achieved a complete response (95% confidence interval (CI): 37.2–69.9%). Complete response at any time: 33 patients (85%) achieved a complete response at any time during the studies. Glucocorticoid tapering: Weekly mean glucocorticoid doses were reduced by 70.1% after 2 weeks of treatment. By week 8, glucocorticoids were tapered to a clinically meaningful dose of ≤1 mg/kg/day in 28 patients (72%) and to ≤0.5 mg/kg/day in 17 patients (44%). Safety: No new safety concerns were identified during the studies. "MAS in Still's disease is a severe condition characterised by intense hyperinflammation and multiple organ failure. Those affected, including young children, often experience high fevers, liver and spleen enlargement, severe cytopenias, and neurological symptoms," said Lydia Abad-Franch, MD, Head of Research & Development and Medical Affairs and Chief Medical Officer at Sobi. "The results to be presented at ACR indicate that emapalumab could potentially provide a new therapeutic option, offering effective control of MAS symptoms and possibly reducing the need for high-dose glucocorticoids. This represents an important development in the treatment landscape for MAS." Additional key results: Overall response (OR) by week 8: 32 patients (82.4%) achieved an overall response by week 8. OR was observed as early as day 5, with a median time to first OR of 2.3 weeks. Clinical MAS remission: 32 patients (82.1%) achieved investigator-assessed clinical MAS remission at any time , with a median time to clinical remission of 3.3 weeks. Survival rate: 37 patients (94.9%) were alive at week 8. Emapalumab is a monoclonal antibody that neutralises interferon gamma (IFNγ), a key cytokine which contributes to the inflammation and tissue damage seen in MAS. The purpose of these two prospective studies is to assess the efficacy and safety of emapalumab in controlling MAS in patients with Still's disease, including sJIA and AOSD, who had an inadequate response to high-dose glucocorticoids. In May 2024, the US FDA granted emapalumab fast track designation as a potential therapeutic option in patient with MAS. Sobi plans to submit an sBLA for this indication to the FDA in 2024. The data will be presented by Alexei A. Grom, MD, Professor of Paediatrics, Research Director Division of Rheumatology, Cincinnati Children's Hospital Medical Centre, in a session entitled "Efficacy and Safety of emapalumab in children and adults with macrophage activation syndrome (MAS) in Still's disease: Results from a phase 3 study and a pooled analysis of two prospective trials" on Tuesday, 19 November at ACR Convergence. About macrophage activation syndrome (MAS) Macrophage activation syndrome (MAS) is a severe complication of rheumatic diseases, most frequently systemic juvenile idiopathic arthritis (sJIA) – a rare systemic disorder of auto-inflammatory nature with common clinical manifestations such as daily spiking fever, typical transient cutaneous rash, arthritis, lymphadenopathy, hepatosplenomegaly and serositis. MAS is characterised by fever, hepatosplenomegaly, liver dysfunction, cytopenias, coagulation abnormalities and hyperferritinaemia, possibly progressing to multiple organ failure and death. MAS is classified as a secondary form of haemophagocytic lymphohistiocytosis (HLH). About emapalumab Emapalumab (Gamifant®) is an anti-interferon gamma (IFNγ) monoclonal antibody that binds to and neutralises IFNγ. In the USA, emapalumab is indicated for the treatment of adult and paediatric (newborn and older) patients with primary haemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. Primary HLH is a rare syndrome of hyperinflammation that usually occurs within the first year of life and can rapidly become fatal unless diagnosed and treated. The FDA approval is based on data from the phase 2/3 studies (NCT01818492 and NCT02069899). Gamifant is indicated for administration through intravenous infusion over one hour twice per week until haematopoietic stem cell transplantation (HSCT). About Sobi® Sobi® is a specialised international biopharmaceutical company transforming the lives of people with rare and debilitating diseases. Providing reliable access to innovative medicines in the areas of haematology, immunology, and specialty care, Sobi has approximately 1,800 employees across Europe, North America, the Middle East, Asia, and Australia. In 2023, revenue amounted to SEK 22.1 billion. Sobi's share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com and LinkedIn. Contacts For details on how to contact the Sobi Investor Relations Team, please click here. For Sobi Media contacts, click here. This information was brought to you by Cision The following files are available for download: SOURCE Swedish Orphan Biovitrum AB WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Vivet Therapeutics Presents Three Posters on Cerebrotendinous Xanthomatosis Program and Novel AAV Gene Delivery Platform at European Society of Gene and Cell Therapy Annual Congress 2024 Paris, France, October 22, 2024 – Vivet Therapeutics (“Vivet”), a clinical stage biotech company developing novel and long-lasting gene therapies for rare inherited liver metabolic disorders, today announces the presentation of three posters demonstrating key pre-clinical findings for its gene therapy program, VTX-806 for the treatment of Cerebrotendinous Xanthomatosis (CTX), a study on S/MAR-containing AAV vector integration in hereditary tyrosinemia type I (HT1) and validation of the translational value of the B6.129-Cyp27a1tmlEl t/J CTX mouse model at the European Society for Gene and Cell Therapy (ESGCT) 2024 Congress Rome, Italy from the 22-25 October. Dr Gloria Gonzalez-Aseguinolaza, Co-Founder & Chief Scientific Officer at Vivet Therapeutics, said, “Our findings highlight the potential of our diversified gene therapy pipeline, using our precise, highly engineered, next-generation viral vectors and gene constructs. We are committed to developing long-lasting AAV-based gene therapies for CTX and other rare inherited liver metabolic disorders to ultimately provide more effective treatment options for patients. Dr Jean-Philippe Combal, Co-Founder & Chief Executive Officer at Vivet Therapeutics added, “The existing standard of care (SOC) for CTX is a lifelong treatment using chenodeoxycholic acid which reduces the levels of toxic metabolites but does not 100% prevent neurodegeneration, leaving an unmet medical need. Our preclinical findings for VTX-806 provide further evidence that VTX-806 holds promise for curative treatment for CTX as underlined by our data and the European Orphan Drug Designation received in September of this year. We look forward to presenting further groundbreaking data at upcoming scientific conferences as we drive the program forward.” Poster one entitled “Long-term metabolic, phenotypic, and neuropathological characterization of the Cyp27a1-/- mouse model of cerebrotendinous xanthomatosis,” details the long-term evaluation of B6.129-Cyp27a1tmlEl t/J, a CTX mouse model with full metabolic, phenotypic, histological and neuropathological characterization up to 18 months of age. The study confirmed prior literature in that Cyp27a1-/- mice when compared to their wild-type (WT) littermates, had hepatomegaly, increased levels of plasma ALT, and increased expression of Cyp7a1 and Cyp3a11. Cyp3a11 is a homolog to human CYP3A4, an enzyme that metabolizes large portions of drugs and other foreign objects in the body. At six months of age, Cyp27a1-/- mice presented lower body weight gain and steatosis, alongside elevated toxic bile acid precursors in circulation and in the brain. In addition, Cyp27a1-/- mice presented signs of ataxia, particularly in females, making this study the first to show measurable motor alterations in a mouse model with CTX, like those described in CTX patients, making this a valuable model for translational CTX research. Poster two entitled “S/MAR-Containing AAV Vectors Result in an Increase in AAV Episomes and a Reduction in AAV Integration Sites in a Mouse Model With a High Rate of Hepatocyte Proliferation,” details an S/MAR (scaffold/matrix attachment region) containing AAV vector integration study in an HT1 mouse model (Fah1R Tyrc/RJ). Results showed that the S/MAR-containing AAVs achieved a higher therapeutic effect than the control vector. Surviving mice showed body weight (BW) and serum biomarker (SB) normalization after approximately 50 days post-injection and the number of viral genomes and disease-associated enzyme (Hfah) expression levels were similar across experimental groups. Immunohistochemistry (IHC) also showed FAH expression in clusters of positive hepatocytes in recovered mice, suggesting potential AAV integration and clonal expansion. These results not only indicate the presence of the S/MAR sequence but also suggest the location of the S/MAR sequence within the therapeutic vector, influences the fate of the viral genome in the transduced cell. Poster three entitled “Liver-directed gene therapy normalizes toxic bile acid metabolite levels in the blood and brain of mice with cerebrotendinous xanthomatosis,” details the development and optimization of VTX-806, as an adeno-associated virus (AAV) vector with high potency and low immunogenicity. AAVs were optimized using Cyp27a1 expression cassettes containing a liver-specific promoter designed to prevent potential activation of an innate immune response and added regulatory elements: minute virus of mice small intron (MVM) and Woodchuck Hepatitis Virus post-transcriptional regulatory element (WPRE). Results demonstrated in vitro and in vivo higher Cyp27a1 expression with VTX-806, restoring normal levels of circulating 7αC4, expression of hepatic bile acid synthesis-related genes, and corrected hepatomegaly. Importantly, normal levels of 7αC4 were restored in the brain. These results demonstrate for the first time that liver-directed AAV gene therapy can normalize levels of toxic metabolites in the brain, offering a potentially effective and curative treatment option for CTX patients. Details of poster presentations are as follow: Poster Title: Long-term metabolic, phenotypic, and neuropathological characterization of the Cyp27a1-/- mouse model of cerebrotendinous xanthomatosis Poster Number: P0381Presenter: Laia Trigueros Motos, Research Scientist at Vivet TherapeuticsDate and Time: Tuesday 22 October at 19:30-21:00 CESTLocation: Forum Poster Title: S/MAR-Containing AAV Vectors Result in an Increase in AAV Episomes and a Reduction in AAV Integration Sites in a Mouse Model With a High Rate of Hepatocyte Proliferation Poster Number: P0138Presenter: Andrea Llanos Ardaiz, PhD Apprentice at Vivet TherapeuticsDate and Time: Wednesday 23 October at 13:30-15:00 CESTLocation: Concourse Level – 1 and Mezzanine Concourse Poster Title: Liver-directed gene therapy normalizes toxic bile acid metabolite levels in the blood and brain of mice with cerebrotendinous xanthomatosis Poster Number: P0888Presenter: Laia Trigueros Motos, Research Scientist at Vivet TherapeuticsDate and Time: Thursday 24 October at 18:00-19:30 CESTLocation: Concourse Level – 1 and Mezzanine Concourse Poster 1 Authors: L Trigueros-Motos3,‡, A Molina1,2,‡, G Pérez1,2, I Marcilla1,2, M Molina1,2, L Neri3, D Moreno-Luqui1,2, A Douar4, JP Combal4, A García-Osta 1,2, M Cuadrado-Tejedor 1,2, B Tamarit4, C Bouquet4, G Despres5, P Krasniqi5, A Lamazière5, 6, R Hernandez-Alcoceba1, G González-Aseguinolaza1,2,3,* 1 Division of DNA and RNA Medicine, CIMA, University of Navarra, Pamplona, Spain 2 Institute for Sanitary Research (IdiSNA), Pamplona, Spain 3 Vivet Therapeutics S.L., Spain 4 Vivet Therapeutics S.A.S., Paris, France 5 Sorbonne Université, Saint Antoine Research Center, INSERM UMR 938, Paris, France 6 Département de Métabolomique Clinique, Hôpital Saint Antoine, AP-HP, Sorbonne Université, Paris, France ‡Equal contribution, *ggonzalez@vivet-therapeutics.com Poster 2 Authors: A Llanos-Ardaiz1, A Lantero1, M Ruiz de Galarreta1, L Neri1, I Mauleón 2, M Bilbao-Arribas 2,3, B Tamarit4, V Ferrer4, A Douar4, JP Combal4, R Aldabe2, G Gonzalez-Aseguinolaza 1,2 1 Vivet Therapeutics S.L., Pamplona, Spain. 2 DNA & RNA Medicine Division, Centre for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. 3 IdISNA, Navarra Institute for Health Research, Pamplona, Spain. 4 Vivet Therapeutics S.A.S., Paris, France Poster 3 Authors: A Molina1,2,‡, L Trigueros-Moto 3,‡, G Pérez1,2, M Molina1,2, I Marcilla-García1,2, L Neri3, A Douar4, JP Combal4, B Tamarit4, C Bouquet 4, P Krasniqi 5, A Lamazière5, 6, R Hernandez-Alcoceba1, G González-Aseguinolaza1,2,3,* 1 Division of DNA and RNA Medicine, CIMA, University of Navarra, Pamplona, Spain 2 Institute for Sanitary Research (IdiSNA), Pamplona, Spain 3 Vivet Therapeutics S.L., Spain 4 Vivet Therapeutics S.A.S., Paris, France 5 Sorbonne Université, Saint Antoine Research Center, INSERM UMR 938, Paris, France 6 Département de Métabolomique Clinique, Hôpital Saint Antoine, AP-HP, Sorbonne Université, Paris, France ‡Equal contribution, *ggonzalez@vivet-therapeutics.com -Ends- For further information, please contact: Optimum Strategic Communications Mary Clark, Zoe Bolt, Vareen OuthonesackTel: +44 (0) 20 3882 9621Email: vivet@optimumcomms.com About Vivet Therapeutics Vivet Therapeutics is a private, clinical-stage biotech company developing novel and long-lasting gene therapies for rare inherited metabolic conditions, including Wilson’s Disease. Vivet’s gene therapy platform uses recombinant adeno-associated viruses (rAAVs) as vectors and has initiated two clinical programs and four pre-clinical assets to date. Its most advanced program VTX-PID, is aimed at depleting Neutralizing Antibodies (NAbs) levels for a given AAV serotype and is advancing in a Phase 1 dose escalating study in Nabs+ subjects. Its Leading pre-clinical program VTX-806, for the treatment of Cerebrotendinous Xanthomatosis (CTX), received ODD by the EC in September 2024 and is demonstrating its potential as an alternative treatment option for patients affected by the burden of CTX. Vivet Therapeutics was founded in 2016 by CEO Dr Jean-Philippe Combal and CSO Dr Gloria Gonzalez-Aseguinolaza and is led by a highly experienced management team with deep expertise developing gene therapies and orphan drugs. Vivet Therapeutics was founded in 2016 by CEO Dr Jean-Philippe Combal and CSO Dr Gloria Gonzalez-Aseguinolaza and is led by a highly experienced management team with deep expertise developing gene therapies and orphan drugs. Vivet Therapeutics is backed by international life science investors including Novartis Venture Fund, Roche Venture Fund, HealthCap, Pfizer Inc., Columbus Venture Partners, Ysios Capital, Kurma Partners and Eurazeo. In 2019, key investor Pfizer contributed a €45M investment to collaborate with Vivet in recognition of its scientific expertise and innovative technology platforms. For more information, please visit www.vivet-therapeutics.com - Follow us on LinkedIn @Vivet Therapeutics and Twitter @Vivet_tx…………………………

October 19, 2024 5:09 pm ET – Novel Investigational Combination Regimen is Advancing to Phase 3 and has the Potential to Become the First Weekly Oral HIV Treatment – Foster City, Calif., & Rahway, N.J. [October 19, 2024] – (BUSINESS WIRE) 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. IMPORTANT U.S. SAFETY INFORMATION AND INDICATION FOR THE USE OF BIKTARVY Biktarvy is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 14 kg who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known or suspected substitutions associated with resistance to bictegravir or tenofovir. BOXED WARNING: POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue BIKTARVY. If appropriate, anti-hepatitis B therapy may be warranted. Contraindications Coadministration: Do not use BIKTARVY with dofetilide or rifampin. Warnings and precautions Drug interactions: See Contraindications and Drug Interactions sections. Consider the potential for drug interactions prior to and during BIKTARVY therapy and monitor for adverse reactions. Immune reconstitution syndrome, including the occurrence of autoimmune disorders with variable time to onset, has been reported. New onset or worsening renal impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with tenofovir alafenamide (TAF)–containing products. Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min except in virologically suppressed adults <15 mL/min who are receiving chronic hemodialysis. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Renal monitoring: Prior to or when initiating BIKTARVY and during therapy, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, assess serum phosphorus. Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue BIKTARVY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations. Adverse reactions Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%). Drug interactions Prescribing information: Consult the full prescribing information for BIKTARVY for more information on Contraindications, Warnings, and potentially significant drug interactions, including clinical comments. Enzymes/transporters: Drugs that induce P-gp or induce both CYP3A and UGT1A1 can substantially decrease the concentration of components of BIKTARVY. Drugs that inhibit P-gp, BCRP, or inhibit both CYP3A and UGT1A1 may significantly increase the concentrations of components of BIKTARVY. BIKTARVY can increase the concentration of drugs that are substrates of OCT2 or MATE1. Drugs affecting renal function: Coadministration of BIKTARVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC and tenofovir and the risk of adverse reactions. Dosage and administration Dosage: Adult and pediatric patients weighing ≥25 kg: 1 tablet containing 50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), and 25 mg tenofovir alafenamide (TAF) taken once daily with or without food. Pediatric patients weighing ≥14 kg to <25 kg: 1 tablet containing 30 mg BIC, 120 mg FTC, and 15 mg TAF taken once daily with or without food. For children unable to swallow a whole tablet, the tablet can be split and each part taken separately as long as all parts are ingested within approximately 10 minutes. Renal impairment: For patients weighing ≥25 kg, not recommended in patients with CrCl 15 to <30 mL/min, or <15 mL/min who are not receiving chronic hemodialysis, or <15 mL/min who are receiving chronic hemodialysis and have no antiretroviral treatment history. For patients weighing ≥14 kg to <25 kg, not recommended in patients with CrCl <30 mL/min. Hepatic impairment: Not recommended in patients with severe hepatic impairment. Prior to or when initiating: Test patients for HBV infection. Prior to or when initiating, and during treatment: As clinically appropriate, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus. Pregnancy and lactation Pregnancy: BIKTARVY is recommended in pregnant individuals who are virologically suppressed on a stable ARV regimen with no known substitutions associated with resistance to any of the individual components of BIKTARVY. Lower plasma exposures of BIKTARVY were observed during pregnancy; therefore, viral load should be monitored closely during pregnancy. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for BIC, FTC, or TAF show no difference in the rates of birth defects compared with a US reference population. Lactation: Individuals infected with HIV-1 should be informed of the potential risks of breastfeeding. Gilead 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 and additional clinical trials or studies, including those involving lenacapavir; uncertainties relating to regulatory applications and related filing and approval timelines, including potential applications for indications currently under evaluation; the possibility that Gilead may make a strategic decision to discontinue development of these programs 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. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site ( www.sec.gov ). U.S. full Prescribing Information for Biktarvy, including BOXED WARNING , is available at www.gilead.com . Biktarvy, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. All other marks are the property of their respective owners. For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on X ( @Gilead Sciences ) and LinkedIn , 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 Julie Cunningham, Media julie.cunningham@merck.com Peter Dannenbaum, Investors peter.dannenbaum@merck.com