Gilead Sciences, Inc. (Nasdaq: GILD) today announced the upcoming presentation of new data from the company’s HIV, hepatitis C virus (HCV), and COVID-19 research and development programs at the 28th Conference on Retroviruses and Opportunistic Infections (virtual CROI 2021) taking place from March 6-10. The breadth of data at the meeting reflects Gilead’s longstanding commitment to applying its scientific innovation toward addressing some of the world’s most challenging viruses and advancing global health.
“The impact of COVID-19 on its own has been devastating for public health, and the disruption to the healthcare system and worsening health inequity driven by the pandemic are threatening to set back efforts to end the HIV epidemic and the hard-won progress toward HCV elimination,” said Diana Brainard, MD, Senior Vice President, Virology Therapeutic Area, Gilead Sciences. “Now more than ever, there is an urgent need to accelerate and advance innovative antiviral research to help prevent transmission and provide a portfolio of therapeutic options for those affected. The data we will present at CROI 2021 demonstrate the important scientific advancements we have made to help address the needs of people living with HIV and HCV, and those affected by COVID-19.”
At CROI 2021, Gilead will share new findings on daily and long-acting HIV prevention and treatment strategies, as well as updates from the company’s continued pursuit of a cure for HIV.
Data will include Phase 2/3 CAPELLA trial results evaluating the company’s investigational, long-acting HIV-1 capsid inhibitor, lenacapavir, in heavily treatment-experienced people with multidrug resistant HIV-1 infection. The company will also present data from a pre-clinical study evaluating lenacapavir for HIV pre-exposure prophylaxis (PrEP).
Insights from Gilead’s cure research program include new data on vesatolimod, an investigational toll-like receptor 7 (TLR7) agonist, as well as analyses of analytical treatment interruption studies using mathematical modelling techniques and approaches for assessing broadly neutralizing antibodies (bNAbs) sensitivity.
HIV treatment research includes long-term data from two Phase 3 studies (Study 1489 and Study 1490) that demonstrated the safety and efficacy profile of the once-daily, single tablet regimen, Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) compared with dolutegravir (DTG)-containing regimens for the treatment of HIV-1 infection in treatment-naïve adults. The data include a sub-analysis in participants with certain transmitted drug resistance and cumulative outcomes from an open-label extension (OLE) phase of two Phase 3 studies evaluating treatment outcomes in participants who initiated therapy with Biktarvy and those who switched to Biktarvy from a DTG-containing regimen.
Results from the ACTG A5360 Study will be presented on the minimal monitoring (MINMON) approach to HCV treatment with Epclusa® (400 mg sofosbuvir/100 mg velpatasvir) across a range of settings and in key populations most impacted by the virus.
Please refer to the full Prescribing Information for complete monitoring information for Epclusa.
Gilead will also present preliminary data from the ongoing Phase 2/3 CARAVAN study evaluating the safety and efficacy of Veklury® (remdesivir) for the treatment of hospitalized pediatric patients two months to 17 years of age. Additional data from an open-label, Phase 3 trial evaluating Veklury's impact on kidney function in patients with moderate COVID-19 will also be presented. Veklury is the only approved antiviral for the treatment of COVID-19.
Select accepted abstracts are as follows:
Investigational Long-Acting HIV Research (Lenacapavir)
Potent Antiviral Activity of Lenacapavir in Phase 2/3 in Heavily ART-experienced PWH
Long-acting HIV Capsid Inhibitor Effective as PrEP in a SHIV Rhesus Macaque Model
Clinical Evaluation of Drug Interactions With Oral Lenacapavir and Probe Drugs
Activity and Resistance Characterization of the HIV Capsid Inhibitor Lenacapavir
Pharmacokinetics of Lenacapavir, an HIV-1 Capsid Inhibitor, in Hepatic Impairment
HIV Treatment Research
Four-Year Outcomes of B/F/TAF in Treatment-Naïve Adults
HIV With Transmitted Drug Resistance is Durably Suppressed by B/F/TAF at Week 144
HIV-1 DNA Genotyping is Often Variable in Repeat Testing From Single Blood Draws
Drug Interactions With Once-Daily B/F/TAF in Combination With Once-Weekly Rifapentine
HIV Prevention Research
Ultrasensitive HIV-1 Drug-Resistance Analysis in the DISCOVER PrEP Trial
HIV Cure Research
Mathematical Modeling of Predictors of Posttreatment Control in HIV Cure Trials
HIV Rebound in Controllers is Associated With Specific Fecal Microbiome Profile
Evaluation of bNAb Sensitivity by Genotyping and Phenotyping for HIV Clinical Trials
Activating PKC-ε Induces HIV Expression With Improved Tolerability
Safety and Efficacy of Remdesivir in a Pediatric COVID-19 Population
Treatment and Outcomes of COVID-19 in the U.S.: Are They Different According to Race?
Acute Kidney Injury in Patients With Moderate COVID-19 Treated With Remdesivir Versus SoC
Remdesivir Versus Standard of Care for Severe COVID-19
A Simple and Safe Approach to HCV Treatment: Findings From the A5360 (MINMON) Trial
For more information, including a complete list of abstracts, click here.
Please see below for U.S. Indications and Important Safety Information, including Boxed Warnings, for Biktarvy®, Descovy®, Descovy for PrEP®, and Epclusa®. Please also see below for U.S. Indication and Important Safety Information for Veklury®.
Lenacapavir and vesatolimod are investigational compounds and are not approved by the U.S. Food and Drug Administration or any other regulatory authority for any use. Their safety and efficacy are unknown. In May 2019, FDA granted Breakthrough Therapy Designation for the development of lenacapavir for the treatment of HIV-1 infection in heavily treatment-experienced patients with multi-drug resistance.
The use of Biktarvy in individuals with known resistance to the components of Biktarvy is investigational, and the safety and efficacy of Biktarvy for this use have not been established.
There is no cure for 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 U.S. 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.
U.S. Important Safety Information for Descovy for PrEP
BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF DESCOVY FOR PrEP IN UNDIAGNOSED EARLY HIV-1 INFECTION and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B
- Descovy for PrEP must be prescribed only to patients confirmed to be HIV negative immediately prior to initiation and at least every 3 months during use. Drug-resistant HIV-1 variants have been identified with use of emtricitabine/tenofovir disoproxil fumarate
- (FTC/TDF) for HIV-1 PrEP following undetected acute HIV-1 infection. Do not initiate if signs or symptoms of acute HIV-1 infection are present unless HIV-negative status is confirmed.
- Severe acute exacerbations of hepatitis B have been reported in patients infected with hepatitis B virus (HBV) who discontinued products containing FTC and/or TDF and may occur with discontinuation of Descovy. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients with HBV who discontinue Descovy. If appropriate, anti-hepatitis B therapy may be warranted.
- Descovy for PrEP is contraindicated in patients with unknown or positive HIV status.
Comprehensive management to reduce risks:
- Use Descovy for PrEP to reduce the risk of HIV-1 infection as part of a comprehensive strategy that includes adherence to daily dosing and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs).
- HIV-1 risk factors: Behavioral, biological, or epidemiologic HIV-1 risk factors may include, but are not limited to: condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high-prevalence area or network.
- Reduce STI risk: Counsel on the use of STI prevention measures (e.g., consistent and correct condom use, knowledge of partner's HIV-1 viremic status, regular testing for STIs).
- Reduce potential for drug resistance: Only prescribe Descovy for PrEP to patients confirmed to be HIV negative immediately prior to initiation, at least every 3 months while taking Descovy, and upon an STI diagnosis. HIV-1 resistance substitutions may emerge in patients with undetected HIV-1 infection who are taking only Descovy because Descovy alone is not a complete regimen for treating HIV-1.
- Some HIV tests may not detect acute HIV infection. Prior to initiating Descovy for PrEP, ask patients about potential recent exposure events. If recent (<1 month) exposures are reported or suspected, or symptoms of acute HIV infection (e.g., fever, fatigue, myalgia, skin rash) are present, confirm HIV-negative status with a test approved by the FDA for use in the diagnosis of acute HIV infection.
- If HIV-1 infection is suspected or if symptoms of acute infection are present while taking Descovy for PrEP, convert the Descovy for PrEP regimen to a complete HIV treatment regimen until HIV-negative status is confirmed by a test approved by the FDA for use in the diagnosis of acute HIV infection.
- Counsel on adherence: Counsel patients to strictly adhere to daily dosing, as efficacy is strongly correlated with adherence. Some patients, such as adolescents, may benefit from more frequent visits and counseling.
Warnings and precautions:
- New onset or worsening renal impairment: Cases of acute renal failure and Fanconi syndrome have been reported with the use of tenofovir prodrugs. Do not initiate Descovy 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 Descovy in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients (see Dosage and Administration section).
- Lactic acidosis and severe hepatomegaly with steatosis: Fatal cases have been reported with the use of nucleoside analogs, including FTC and TDF. Discontinue use 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 (≥2%) in the Descovy for PrEP clinical trial were diarrhea, nausea, headache, fatigue, and abdominal pain.
- Prescribing information: Consult the full Prescribing Information for Descovy for more information, warnings, and potentially significant drug interactions, including clinical comments.
- Metabolism: Drugs that inhibit P-gp can increase the concentrations of tenofovir alafenamide (TAF), a component of Descovy. Drugs that induce P-gp can decrease the concentrations of TAF, which may lead to loss of efficacy.
- Drugs affecting renal function: Coadministration of Descovy 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: One tablet taken once daily with or without food.
- HIV screening: Test for HIV-1 infection immediately prior to initiating, at least every 3 months during use, and upon diagnosis of an STI (see Warnings and Precautions section).
- HBV screening: Test for HBV infection prior to or when initiating Descovy.
- Renal impairment and monitoring: Not recommended in patients with creatinine clearance (CrCl) <30 mL/min. Prior to or when initiating Descovy, and during use on a clinically appropriate schedule, assess serum creatinine, CrCl, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, assess serum phosphorus.
U.S. Indication for Descovy for PrEP
Descovy for PrEP is indicated in at-risk adults and adolescents (≥35 kg) to reduce the risk of sexually acquired HIV-1 infection, excluding individuals at risk from receptive vaginal sex. HIV-1–negative status must be confirmed immediately prior to initiation.
Limitation of Use:
- Descovy for PrEP is not indicated in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated.
U.S. Important Safety Information 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.
- 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 Concomitant Use of Epclusa 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.
- The most common adverse reactions (≥10%, all grades) with Epclusa were headache and fatigue; and when used with RBV in decompensated cirrhotics were fatigue, anemia, nausea, headache, insomnia, and diarrhea.
- 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.
U.S. Indication for Epclusa
Epclusa is indicated for the treatment of patients 6 years of age and older or weighing at least 17 kg with chronic hepatitis C virus (HCV) 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 Veklury
- Veklury is contraindicated in patients with a history of clinically significant hypersensitivity reactions to Veklury or any of its components.
Warnings and precautions
- Hypersensitivity, including infusion-related and anaphylactic reactions: Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed during and following administration of Veklury. Monitor patients under close medical supervision for hypersensitivity reactions during and following administration of Veklury. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time ≤120 minutes) can potentially prevent these reactions. If a severe infusion-related hypersensitivity reaction occurs, immediately discontinue Veklury and initiate appropriate treatment (see Contraindications).
- Increased risk of transaminase elevations: Transaminase elevations have been observed in healthy volunteers and in patients with COVID-19 who received Veklury; these elevations have also been reported as a clinical feature of COVID-19. Perform hepatic laboratory testing in all patients (see Dosage and administration). Consider discontinuing Veklury if ALT levels increase to >10x ULN. Discontinue Veklury if ALT elevation is accompanied by signs or symptoms of liver inflammation.
- Risk of reduced antiviral activity when coadministered with chloroquine or hydroxychloroquine: Coadministration of Veklury with chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on data from cell culture experiments, demonstrating potential antagonism, which may lead to a decrease in antiviral activity of Veklury.
- The most common adverse reaction (≥5% all grades) was nausea.
- The most common lab abnormalities (≥5% all grades) were increases in ALT and AST.
- Drug interaction trials of Veklury and other concomitant medications have not been conducted in humans.
Dosage and administration
- Dosage: For adults and pediatric patients ≥12 years old and weighing ≥40 kg: 200 mg on Day 1, followed by once-daily maintenance doses of 100 mg from Day 2 administered only via intravenous infusion over 30 to 120 minutes.
- Treatment duration: For patients not requiring invasive mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO): 5 days; may be extended up to 5 additional days (10 days total) if clinical improvement is not observed. For patients requiring invasive mechanical ventilation and/or ECMO: 10 days.
- Testing prior to and during treatment: Perform eGFR, hepatic laboratory, and prothrombin time testing prior to initiating Veklury and during use as clinically appropriate.
- Renal impairment: Veklury is not recommended in individuals with eGFR <30 mL/min.
- Dose preparation and administration: See full Prescribing Information.
Pregnancy and lactation
- Pregnancy: There are insufficient human data on the use of Veklury during pregnancy. Pregnant women hospitalized with COVID-19 are at risk for serious morbidity and mortality. Veklury should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
- Lactation: It is not known whether Veklury can pass into breast milk. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.
U.S. Indication for Veklury
Veklury is indicated for adults and pediatric patients (12 years of age and older and weighing at least 40 kg) for the treatment of COVID-19 requiring hospitalization. Veklury should only be administered in a hospital or in a healthcare setting capable of providing acute care comparable to inpatient hospital care.
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 and cancer. Gilead operates 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, millions of people living with HIV globally receive antiretroviral therapy provided by Gilead or one of the company’s manufacturing partners.
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, including those involving Biktarvy, Descovy for PrEP, Epclusa, Veklury, lenacapavir and vesatolimod and the possibility that Gilead may be unable to complete one or more of such trials in the currently anticipated timelines or at all. In addition, it is possible that Gilead may make a strategic decision to discontinue development of lenacapavir and vesatolimod, or that FDA and other regulatory agencies may not approve lenacapavir or GS-CA1, and any marketing approvals, if granted, may have significant limitations on its use. As a result, lenacapavir and vesatolimod may never be successfully commercialized. These and other risks are described in detail from time to time in Gilead’s periodic reports filed with the U.S. Securities and Exchange Commission, including current reports on Form 8-K, quarterly reports on Form 10-Q and annual reports on Form 10-K. 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. Investors are cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and are 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 to update any such forward-looking statements.
U.S. Prescribing Information for Biktarvy, Descovy for PrEP, and Epclusa including BOXED WARNINGS, and U.S. Prescribing Information for Veklury, are available at www.gilead.com.
Biktarvy, Descovy for PrEP, Epclusa, Veklury, 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 www.gilead.com, follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.