-- Real-World Evidence from More than 850,000 Hospitalized Patients Provides Clinical Insights on the Use of Veklury (Remdesivir) as Stand of Care COVID-19 Treatment --
-- New Post-hoc Analysis of Non-Hospitalized COVID-19 Patients in the Phase 3 PINETREE Study Demonstrates Veklury Treatment Initiated Within 5 Days of Symptoms Reduced Risk for Hospitalization by 90% --
Gilead Sciences, Inc. (Nasdaq: GILD) today announced findings from two studies, which provide further insights on the use of Veklury ® (remdesivir) for the treatment of hospitalized and non-hospitalized patients with COVID-19. The first study is a retrospective observational analysis of the real-world treatment data from the Premier Healthcare Database consisting of 853,219 patients hospitalized with COVID-19 across the United States. This analysis found that more than 50% of hospitalized COVID-19 patients received Veklury, predominantly in combination with other therapies. An oral presentation of this real-world data analysis will be given on April 25 at 11 a.m. Western European Summer Time in Hall P at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022). A separate study, which is a new post-hoc analysis of data from the Phase 3 PINETREE study, demonstrated that use of Veklury within five days of symptom onset or between 5 to 7 days of symptom onset reduced hospitalizations in patients at high risk for severe COVID-19 disease. This post-hoc analysis was presented as a poster (#L0447) at ECCMID.
The observational analysis of real-world data also found that as the pandemic progressed, initiation of Veklury within two days of hospitalization increased from 41% to 91% between May 2020 and December 2021. During this period, as new variants arose and disease severity fluctuated, median hospital length of stay (LOS) decreased from seven to six days with the greatest benefit in invasive mechanical ventilation/ ECMO patients (15 to 11 days). While ICU use decreased from 34% to 27%, with the greatest benefit in high-flow oxygen/non-invasive ventilation (66% to 52%), overall ICU LOS remained the same. Overall mortality rates remained stable at 16%, with the greatest decline over time in patients on low-flow supplemental oxygen (15% to 12%). These results confirm Veklury's position as a foundational treatment for hospitalized patients with COVID-19 and signify the need to treat patients early before they become more severely ill with COVID-19.
"In a pandemic, real world analysis has a particularly important role in helping us understand how treatment choices are evolving over time as we work to discover the most effective treatment options for patients. We've long understood that antivirals work optimally for respiratory viruses when they are given as early as possible, without delay. This data confirms that antiviral treatment is now initiated sooner in hospitalizations and that throughout the pandemic, remdesivir has remained the foundation for hospitalized patients with COVID-19," said Robert L. Gottlieb, MD, PhD, Baylor University Medical Center and Baylor Scott & White Research Institute. "Additionally, as healthcare providers' experience and confidence in COVID-19 therapeutic options has increased, so too has the use of therapeutic combinations, reflecting the incremental incorporation of evidence-based therapies."
The new post-hoc analysis from a Phase 3 double-blind, placebo-controlled trial (PINETREE) demonstrating that a three-day course of Veklury treatment significantly reduced the risk of hospitalization was also presented at ECCMID. The analysis assessed the variability of treatment effect with Veklury by time of symptom onset and number of baseline risk factors. The study concluded that Veklury reduced hospitalizations in patients at high risk for severe COVID-19 disease when initiated anytime within a 7-day window from symptom onset. As expected with antiviral therapy, the benefit was modestly greater the sooner Veklury was administered. Patients treated with Veklury within five days of symptom onset had a 90% reduced risk for hospitalization. Additionally, patients who received Veklury after five 5 days of symptom onset experienced an 81% reduction in risk of hospitalization. This new analysis builds on the previously presented primary endpoint analysis, in which Veklury demonstrated a statistically significant 87% reduction in risk for the composite primary endpoint of COVID-19 related hospitalization or all-cause death by Day 28 (0.7% [2/279]) compared with placebo (5.3% [15/283]) p=0.008); no deaths occurred in either arm of the study through the primary endpoint.
"The data presented at ECCMID, not only underscore Veklury as the antiviral standard of care for COVID-19 treatment in hospitalized patients, but they also further emphasize that patients can benefit from Veklury when it's given up to seven days after the onset of symptoms and that the benefit is greater the sooner it is administered," said Frank Duff, Senior Vice President, Virology Therapeutic Head, Gilead Sciences. "As the pandemic has progressed and the utility of other treatments against new variants has shifted, we are proud that Veklury has remained the foundation for patients hospitalized with COVID-19."
Gilead presented two additional studies from the company's COVID-19 clinical and real-world evidence programs at the conference.
- Data from the CARAVAN study evaluated safety, pharmacokinetic, virologic, and clinical outcomes of Veklury treatment in pediatric patients who were 28 days of age and older. The interim analysis of Veklury in pediatric patients hospitalized with COVID-19 with ages ranging from 28 days to less than 18 years demonstrated that Veklury was generally well tolerated, with a high proportion of participants showing clinical improvement and recovery. Overall, no new safety findings for Veklury were noted. In the study, 75% and 85% showed clinical improvement (≥2 point increase on the ordinal scale) at Day 10 and last assessment, respectively, while 60% and 83% were discharged by Day 10 and Day 30, respectively. Overall, 38 patients (72%) experienced AEs, with 11 patients (21%) experiencing serious adverse events (SAEs) that were determined not to be study-drug related, including 3 participant deaths which were consistent with the patients' underlying medical condition prior to study entry or with COVID-19 disease during hospitalization.
- A real-world evidence analysis evaluated data from 2,310 patients hospitalized with COVID-19 who had previously undergone kidney transplantation. The analysis found that in this patient population, overall mortality was comparable to the general population hospitalized with COVID-19, but markedly increased for those with diminished renal function, comorbidities, and higher oxygen requirements upon admission. Insights from this study help inform clinical decision-making in the context of management of kidney transplant patients and other solid-organ transplant recipients, alike.
Veklury (remdesivir) is a nucleotide analog invented by Gilead, building on more than a decade of the company's antiviral research. Veklury is a foundation 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 drug interactions in diverse populations. At this time, more than half of patients hospitalized with COVID-19 in the United States are treated with Veklury. It can help reduce disease progression across a spectrum of disease severity and enable patients to recover faster, freeing up limited hospital resources and saving healthcare systems money.
Veklury was approved by the FDA in October 2020, 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. In January 2022, the FDA approved a supplemental NDA to expand the indication to non-hospitalized adult and adolescent patients who are at high risk of progression to severe COVID-19, including hospitalization or death. This allows for Veklury to be administered in qualified outpatient settings that can administer daily intravenous (IV) infusions over three consecutive days. Veklury also has an Emergency Use Authorization (EUA) for non-hospitalized pediatric patients weighing at least 3.5 kg who are younger than 12 years of age or weighing less than 40 kg who are at high risk of disease progression, in addition to those with COVID-19 requiring hospitalization. Veklury is contraindicated in patients who are allergic to Veklury or any of its components; please see below for additional Important Safety Information for Veklury.
Veklury continues to demonstrate durable activity against SARS-CoV2 as it evolves. Veklury is a nucleotide analog that directly inhibits viral replication inside of the cell by targeting the SARS-CoV-2 viral RNA polymerase. In vitro laboratory testing in multiple independent studies shows that Veklury continues to demonstrate durable activity against SARS-CoV2 as it evolves, including the Omicron variant and its subvariants BA.1 and BA.2. As new SARS-CoV-2 variants of concern emerge around the world, Gilead continuously evaluates the effectiveness of Veklury against viral variants.
Veklury is approved or authorized for temporary use in approximately 50 countries worldwide. To date, Veklury and generic remdesivir have been made available to more than 11 million patients around the world, including more than 7 million people in 127 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.
U.S. Indication for Veklury
Veklury ® (remdesivir 100 mg for injection) is indicated for the treatment of COVID-19 in adults and pediatric patients (12 years of age and older and weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, who are:
- Hospitalized, or
- Not hospitalized and have mild-to-moderate COVID-19 and are at high risk for progression to severe COVID-19, including hospitalization or death.
Veklury should only be administered in settings in which health care providers have immediate access to medications to treat a severe infusion or hypersensitivity reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary. Veklury must be administered by intravenous infusion. Veklury is contraindicated in patients who are allergic to Veklury or any of its components. 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 occurred within one hour. Monitor patients during infusion and observe for at least one 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 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
- 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. Veklury should be initiated as soon as possible after diagnosis of symptomatic COVID-19.
- Treatment duration:
- For hospitalized patients requiring invasive mechanical ventilation and/or ECMO, the recommended total treatment duration is 10 days.
- For hospitalized patients not requiring 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 for up to 5 additional days for a total treatment duration of up to 10 days.
- For non-hospitalized patients diagnosed with mild-to-moderate COVID-19 who are at high risk for progression to severe COVID-19, including hospitalization or death, the recommended total treatment duration is 3 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
- Dose preparation and administration: See full Prescribing Information.
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 the possibility of unfavorable results from ongoing or additional studies involving Veklury (remdesivir). 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, 2021, 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 involves 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.
Jacquie Ross, Investors
Nicole Rodriguez, Media