Gilead Sciences, Inc. (Nasdaq: GILD) today announced data demonstrating the safety and efficacy of the once-daily, single tablet regimen Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) in virologically suppressed adults ages 65 and older (n=140), including those with common comorbidities such as diabetes (22 percent), hypertension (55 percent), cardiovascular disease (24 percent), and dyslipidemia, which is an abnormal amount of lipids in the blood (59 percent). At 48 weeks, 92 percent of those who switched to Biktarvy maintained virologic suppression, achieving HIV RNA<50 copies/mL. Across the studies, Biktarvy was generally well tolerated. These data were evaluated as part of a pooled analysis of four international trials and will be presented during the 23rd International AIDS Conference (AIDS 2020: Virtual).
“As the number of older adults living with HIV grows, it’s critical to optimize therapy to fit the unique needs of this key population, including those with chronic conditions who may be on multiple medications,” said Moti Ramgopal, MD, FACP, FIDSA, Medical Director, Midway Immunology and Research Center. “By 2030, it is projected that up to 70 percent of people living with HIV will be 50 years or older, the majority of whom will have at least one other comorbidity. The data presented at AIDS 2020: Virtual showed that adults 65 years and older who switched to Biktarvy maintained viral suppression without a significant impact on lipid levels such as cholesterol, weight, or interactions with other drugs they may be taking for comorbidities.”
Gilead also announced a new data analysis from multiple studies evaluating drug resistance, including the first study to investigate a switch to Biktarvy in virologically suppressed study participants (n=565) in which some of the participants had a history of treatment failure or suspected pre-existing nucleoside reverse transcriptase inhibitor resistance (NRTI-R). The study showed infrequent and similar viral blips (when study participants experienced a temporary viral load at or above 50 copies/mL) among study participants switching to Biktarvy, as compared to the comparator arm. The results support further evaluation of whether the once-daily, single tablet regimen Biktarvy may potentially be an effective and well-tolerated option for adults with a history of treatment failure or pre-existing resistance. The use of Biktarvy in individuals with a history of treatment failure or known resistance to the components of Biktarvy is investigational.
Biktarvy is indicated in the United States as a complete regimen for the treatment of HIV-1 infection in adults or pediatric patients weighing at least 25 kg who have no antiretroviral (ART) treatment history. While it is also indicated for adults and pediatric patients weighing at least 25 kg who are virologically suppressed and on a stable antiretroviral regimen, these people must have no history of treatment failure and no known substitutions associated with resistance to the individual components of Biktarvy. Please see below for U.S. Important Safety Information for Biktarvy, including a Boxed Warning on the risk of post-treatment acute exacerbation of hepatitis B.
“These data presented at AIDS 2020: Virtual further reinforce the potential of Biktarvy for use in a wide range of people living with HIV, including those with treatment resistance, older adults and those with certain common chronic conditions,” said Diana Brainard, MD, Senior Vice President and Virology Therapeutic Area Head, Gilead Sciences. “At Gilead, we are focused on continuing to advance the scientific understanding of HIV treatment in a way that will have a truly meaningful impact on the daily lives of those affected by the epidemic, from young children to the growing number of older adults who are living longer, healthier lives with HIV.”
Key abstracts for HIV treatment data presented at AIDS 2020: Virtual include:
Oral Presentation OAB0403: Pooled Analysis of 4 International Trials of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) in Adults Aged 65 or Older Demonstrating Safety and Efficacy: Week 48 Results
A pooled analysis of four international trials (Studies 1844, 1878, 4030 and 4449) of virologically suppressed (HIV-1 RNA<50 copies/mL), treatment-experienced adults 65 years and older evaluated the efficacy and safety of switching to Biktarvy. The primary endpoint was HIV-1 RNA<50 copies/mL at week 48 as defined by the U.S. Food and Drug Administration Snapshot algorithm. Across the studies, 140 study participants with a median age of 68 years were evaluated; 14 percent were female, and 88 percent were white. Medical history at baseline was significant for diabetes (22 percent), hypertension (55 percent), cardiovascular disease (24 percent), and dyslipidemia, which is an abnormal amount of lipids in the blood (59 percent).
At week 48, the proportion with HIV RNA<50 copies/mL was 92 percent (129/140), showing that Biktarvy in older adults maintained high rates of virologic suppression. In the studies, Biktarvy was generally well-tolerated; 11 study participants experienced a grade 1 or 2 study drug-related adverse event (AE), four of which discontinued the study. No participant experienced a grade 3 or 4 drug-related AE or virologic failure. Most common AEs were nasopharyngitis and arthralgia (7 percent each).
Virtual Poster PEB0257: Baseline NRTI Resistance in Suppressed Participants Did Not Lead to Viral Blips on Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) or Dolutegravir (DTG)+F/TAF Through Week 48 in Study 380-4030
Study 4030 was the first study to prospectively investigate switching to Biktarvy in virologically suppressed study participants (n=565) in which some of the participants (25 percent) had a history of treatment failure and/or known or suspected pre-existing NRTI resistance. The aim of this additional analysis of the 48-week study data was to analyze the occurrence of viral blips in 565 suppressed study participants switching from DTG+F/TAF or DTG+F/tenofovir disoproxil fumarate to Biktarvy or DTG+F/TAF. A blip was defined as a post-baseline HIV-1 RNA value ≥50 c/mL preceded and followed by HIV-1 RNA <50 c/mL.
In total, 15 study participants (2.7 percent) experienced a blip through week 48 with similar blip frequencies between treatment arms. No participant with blips qualified for genotypic and phenotypic testing for emergent resistance. Viral blips were infrequent and similar among study participants switching to Biktarvy or DTG+F/TAF, and baseline NRTI resistance did not result in a higher rate of blips. Blips did not lead to virologic failure or resistance development using these triple therapy regimens.
Virtual Poster PEB0254: Prevalence and Risk Factors of Pre-Existing NNRTI Resistance Among Suppressed PLWH in B/F/TAF Switch Studies
This analysis investigated the prevalence of pre-existing non-nucleoside reverse-transcriptase inhibitor resistance (NNRTI-R) and associated risk factors across four clinical trials evaluating the safety and efficacy of switching stably suppressed adults with HIV-1 infection to Biktarvy.
Pre-existing drug resistance was assessed by historical genotypes and/or retrospective proviral DNA genotyping. Stepwise selection was used to identify potential risk factors for NNRTI-R in a multivariate logistic regression model with variables including participant demographics and baseline characteristics, HIV disease measures, ART history, and other pre-existing HIV drug resistance substitutions.
Baseline genotypic data were available for 1,995 study participants. Altogether, 38 percent (754/1,995) of study participants were previously treated with NNRTIs, and 7 percent (145/1,995) were on a NNRTI-based regimen at baseline. NNRTI resistance was the most frequently observed resistance class in these studies. The high prevalence of NNRTI resistance among suppressed people living with HIV and the risk factors associated with NNRTI resistance underscore the importance of comprehensive resistance assessments and medical history prior to switching to NNRTI containing regimens.
The use of Biktarvy in individuals with a history of treatment failure or known resistance to the components of Biktarvy is investigational; this use is not approved by the U.S. FDA, and the safety and efficacy of Biktarvy for this use has not been established. Please see below for the U.S. Indication for Biktarvy.
Biktarvy does not prevent other sexually transmitted infections or cure HIV or AIDS.
U.S. Important Safety Information for Biktarvy
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.
- 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: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. In clinical trials of BIKTARVY, there have been no cases of Fanconi syndrome or proximal renal tubulopathy (PRT). Do not initiate BIKTARVY in patients with estimated creatinine clearance (CrCl) <30 mL/min. 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.
- Most common adverse reactions (incidence ≥5%; all grades) in clinical studies through week 144 were diarrhea (6%), nausea (6%), and headache (5%).
- 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: Patients weighing ≥25 kg: 1 tablet taken once daily with or without food.
- Renal impairment: 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: There is insufficient human data on the use of BIKTARVY during pregnancy. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects. Discuss the benefit-risk of using BIKTARVY during pregnancy and conception. An Antiretroviral Pregnancy Registry (APR) has been established. Available data from the APR for FTC shows no difference in the rates of birth defects compared with a US reference population.
- Lactation: Women infected with HIV-1 should be instructed not to breastfeed, due to the potential for HIV-1 transmission.
U.S. Indication for Biktarvy
Biktarvy is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 25 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 history of treatment failure and no known resistance to any component of Biktarvy.
About Gilead Sciences
Gilead Sciences, Inc. is a research-based biopharmaceutical company that discovers, develops and commercializes innovative medicines in areas of unmet medical need. The company strives to transform and simplify care for people with life-threatening illnesses around the world. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.
For more than 30 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention, testing and linkage to care, and cure research. Today, it’s estimated that more than 12 million people living with HIV globally receive antiretroviral therapy provided by Gilead or one of the company’s manufacturing partners.
Gilead is committed to supporting the global health community to quickly and effectively respond to serious and life-threatening viral outbreaks worldwide. To that end, we are contributing our antiviral expertise and resources to help investigate potential treatments for patients with COVID-19.
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 the possibility of unfavorable results from ongoing and additional clinical trials involving Biktarvy, and the possibility that we are unable to complete one or more of such trials on the currently anticipated timelines or at all. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
U.S. Prescribing Information for Biktarvy including BOXED WARNING, is available at www.gilead.com.
Biktarvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.
For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
Douglas Maffei, PhD, Investors
Brian Plummer, Media