– Phase 3 Clinical Trial Demonstrated the Safety Profile of Veklury in Patients with Severe Renal Impairment –
– Real-World Evidence Demonstrated Veklury Reduced COVID-19- Associated Mortality and Readmission Rates in Immunocompromised Patients Across All Variants of Concern, Including Omicron –
– Gilead Presents Positive Phase 1 Data for its Investigational Oral COVID-19 Antiviral Treatment, Obeldesivir (GS-5245) –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced positive results from several COVID-19 clinical and real-world evidence studies being presented at the 33rd European Congress of Clinical Microbiology & Infectious Diseases (ECCMID). A Phase 3 clinical study demonstrated that Veklury® (remdesivir) was generally well tolerated in people with moderate to severe renal impairment. Additional data includes a retrospective real-world study which demonstrated that Veklury treatment is associated with a lower risk of death from COVID-19 for people living with cancer. A separate real-world analysis demonstrated that use of Veklury is also associated with reduced hospital readmission risk in immunocompromised patients hospitalized with COVID-19. Results from a Phase 1 study evaluating the safety, tolerability, and pharmacokinetics (PK) of obeldesivir, previously known as GS-5245, a novel investigational oral compound being developed by Gilead for the treatment of SARS-CoV-2 infection, showed obeldesivir reaches expected therapeutic plasma concentrations for the treatment of COVID-19.
“The breadth of clinical and real-world evidence data presented at ECCMID further support the strong efficacy and safety profile of Veklury,” said Frank Duff, MD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “Since the beginning of the pandemic, Veklury has played a critical role in the treatment of hospitalized patients with COVID-19. The real-world data further demonstrates its role in reducing mortality and hospital readmission rates in vulnerable patient populations, including people living with cancer and other immunosuppressed conditions.”
Results from a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study (REDPINE) evaluated the safety of Veklury in patients with moderately and severely reduced kidney function who were hospitalized for COVID-19, a population with increased COVID-19-related mortality. The trial included 243 hospitalized adult participants with confirmed COVID-19 and renal impairment, including 90 participants (37%) with acute kidney injury (AKI), 64 participants (26%) with chronic kidney disease (CKD) and 89 participants (37%) with end stage kidney disease (ESKD) requiring hemodialysis. Patients were randomized 2:1 to receive Veklury (n=163) or placebo (n=80), in addition to standard of care. No new safety signals were observed in the study and no additional adverse reactions to Veklury were identified in 163 hospitalized patients with AKI (n=60), CKD (n=44) or ESKD (n=59) on hemodialysis receiving Veklury for up to 5 days.
Two real-world studies of clinical practice presented at ECCMID examined Veklury’s effectiveness in reducing COVID-19-associated mortality for those living with cancer, as well as the role Veklury plays in reducing hospital readmission for immunocompromised patients infected with dominant variants of concern (VOC): pre-Delta, Delta and Omicron. In the first analysis, 7,482 people with cancer and hospitalized for COVID-19 who were treated with Veklury in the first two days of admission were evaluated. Results at Day 28 showed that people with cancer treated with Veklury had a significantly lower risk for mortality compared to people with cancer that were not treated with Veklury (HR:0.67, 95% CI:0.59-0.75; p<0.0001). This finding was seen across all VOC at Day 28: pre-Delta, 25% (HR:0.75, 95% CI:0.61-0.92; p=0.006); Delta, 32% (HR:0.68, 95% CI:0.55-0.85; p=0.0005); and Omicron, 40% (HR:0.60. 95% CI:0.50-0.72; p<0.0001).
In the second analysis, 4,664 immunocompromised patients were evaluated and those who received treatment with Veklury (n=2,332) had lower risk for hospital readmission at both 30- and 60-day time periods. Results demonstrated that 60-day readmission rates were 16% lower for patients treated with Veklury during the Delta wave (HR:0.84, 95% CI:0.71-0.96; p<0.01) and 13% lower during the Omicron wave (HR:0.87, 95% CI:0.81-0.93; p<0.01) compared to matched controls (n=2,332). These data further confirm RWE presented at CROI earlier this year which demonstrated that use of Veklury was associated with a reduced risk of 30-day all-cause readmission.
“Antivirals play a key role in halting the replication of the SARS-CoV-2 virus. Remdesivir is also an important treatment option for vulnerable patient populations such as the immunocompromised, because it has a well-established safety and tolerability profile and it maintains activity across variants of concern,” said Michele Bartoletti, MD, PhD, Head of Infectious Disease Unit at Humanitas Research Hospital in Milan and Associate Professor of Humanitas University, Milan, Italy.
Gilead also announced positive data at ECCMID from its Phase 1 randomized, double-blind, placebo-controlled, dose escalation study of obeldesivir in healthy adult participants. Results demonstrated that obeldesivir reaches expected therapeutic plasma concentrations for the treatment of COVID-19. Obeldesivir is an investigational novel oral antiviral being developed for the treatment of COVID-19, which once metabolized, works in the same way as Veklury by targeting SARS-CoV-2 virus replication through inhibition of the viral RNA polymerase. Gilead has advanced obeldesivir into two Phase 3 studies – BIRCH and OAKTREE – in broad populations and geographies to assess the efficacy and safety of obeldesivir for the treatment of non-hospitalized participants with COVID-19.
About Gilead’s COVID-19 Development Program
Veklury (remdesivir) is a nucleotide analog invented by Gilead, building on more than a decade of the company’s antiviral research. Veklury is the antiviral standard of care for the treatment of hospitalized patients with COVID-19 and is a recommended treatment for reducing disease progression in non-hospitalized patients at high risk of disease progression. Veklury has an established safety profile and minimal known drug interactions in diverse populations. It plays an important role in reducing disease progression and mortality across a spectrum of disease severity and enabling patients to recover faster.
Complementing randomized clinical trials (RCTs) with these new real-world observational studies of hospitalized patients with COVID-19 further demonstrates the value of Veklury to clinicians and patients, including immunocompromised individuals and other vulnerable populations. Although RCTs remain the best tool for assessing the efficacy and safety of a medicine, RWE provides important complimentary data on a treatment’s use in routine clinical practice. RWE analyses of Veklury from other sources are ongoing and may vary in their results or conclusions.
The clinical benefits of Veklury in hospitalized patients have been established in multiple randomized, controlled Phase 3 clinical trials, including ACTT-1. In 2020, results from ACTT-1 demonstrated that in the overall study population of hospitalized patients with COVID-19, Veklury-treated patients showed a trend toward reduced mortality compared with placebo (11% vs. 15%, HR:0.73, 95% CI:0.52 to 1.03); however, this result was not statistically significant.
Veklury is approved in more than 50 countries worldwide. To date, Veklury and generic remdesivir have been made available to nearly 13 million patients around the world, including more than 8 million people in middle- and low-income countries, through Gilead’s voluntary licensing program. These licenses currently remain royalty-free, reflecting Gilead’s existing commitment to enabling broad patient access to remdesivir.
There remains a significant need to develop new and effective oral treatment options for people with COVID-19. Gilead is also working to advance an investigational oral nucleoside prodrug, obeldesivir, that when metabolized forms the same active metabolite as remdesivir.
About BIRCH (NCT05603143)
BIRCH is a Phase 3, global, randomized, double-blind, placebo-controlled study that will compare the efficacy and safety of obeldesivir with placebo in non-hospitalized participants who are at high risk for developing severe COVID-19. For further information, please see https://www.clinicaltrials.gov/ct2/show/NCT05603143.
About OAKTREE (NCT05715528)
OAKTREE is a Phase 3, global, randomized, double-blind, placebo-controlled study that will evaluate participants without risk factors for developing severe COVID-19 to compare the safety and efficacy of obeldesivir with placebo in non-hospitalized participants with COVID-19, regardless of vaccination status. For further information, please see https://clinicaltrials.gov/ct2/show/NCT05715528.
Obeldesivir is an investigational product that has not been approved for any use globally. The safety and efficacy of obeldesivir have not been established.
U.S. Indication for Veklury
VEKLURY is indicated for the treatment of COVID-19 in adults and pediatric patients (≥28 days old and weighing ≥3 kg), who are:
- Hospitalized, or
- Not hospitalized, have mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death.
For more information, please see the U.S. full Prescribing Information available at www.gilead.com.
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; most reactions occurred within 1 hour. Monitor patients during infusion and observe for at least 1 hour after infusion is complete for signs and symptoms of hypersensitivity as clinically appropriate. Symptoms may include hypotension, hypertension, tachycardia, bradycardia, hypoxia, fever, dyspnea, wheezing, angioedema, rash, nausea, diaphoresis, and shivering. Slower infusion rates (maximum infusion time of up to 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
- Administration should take place under conditions where management of severe hypersensitivity reactions, such as anaphylaxis, is possible.
- For patients who are hospitalized, Veklury should be initiated as soon as possible after diagnosis of symptomatic COVID-19.
- For patients who are hospitalized and do not require invasive mechanical ventilation and/or ECMO, the recommended treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended up to 5 additional days, for a total treatment duration of up to 10 days.
- For patients who are hospitalized and require invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days.
- For patients who are not hospitalized, diagnosed with mild-to-moderate COVID-19, and are at high risk for progression to severe COVID-19, including hospitalization or death, the recommended total treatment duration is 3 days. Veklury should be initiated as soon as possible after diagnosis of symptomatic COVID-19 and within 7 days of symptom onset for outpatient use.
- 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.
Pregnancy and lactation
- Pregnancy: A pregnancy registry has been established. There are insufficient human data on the use of Veklury during pregnancy. COVID-19 is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease and fetal death.
- 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.
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.
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 within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials, including those involving Veklury and obeldesivir; the possibility that Gilead may make a strategic decision to discontinue development of product candidates, including obeldesivir; uncertainties relating to regulatory applications and related filing and approval timelines; the risk that any regulatory approvals, if granted, may be subject to significant limitations on use; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Annual Report on Form 10-K for the year ended December 31, 2022, 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.
U.S. full Prescribing Information for Veklury is available at www.gilead.com.
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.