FDA Approves Veklury® (Remdesivir) to Treat COVID-19 in People With Mild to Severe Hepatic Impairment With no Dose Adjustment

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) approved a supplemental new drug application (sNDA) for the use of Veklury® (remdesivir) with no dose adjustments to treat COVID-19 in people with mild, moderate and severe hepatic impairment. This approval further supports the safety profile of Veklury as the first and only approved antiviral COVID-19 treatment that can be used across all stages of liver disease.

The clinical benefit of Veklury in hospitalized populations with COVID-19 is supported by randomized controlled trials, real-world evidence and meta-analyses, but the pharmacokinetics of Veklury had not previously been evaluated in patients with hepatic impairment. This latest approval is based on results from a Phase 1 study of safety and pharmacokinetics in people with hepatic impairment (GS-US-540-9014). No new safety signals were observed. Based upon these results, the label has been updated to reflect that no dose adjustment is required across all stages of liver disease. The label still recommends initial hepatic laboratory testing in all patients, before starting Veklury and during treatment as clinically appropriate, and that discontinuation be considered if alanine transaminase (ALT) levels increase to 10 times the upper limit of normal or if ALT elevation is accompanied by signs or symptoms of liver inflammation.

More than 100 million people in the U.S. are living with liver disease. Furthermore, people with liver disease represent a population that is vulnerable to COVID-19 and are at increased risk of morbidity and mortality. People with severe liver disease currently have limited treatment options for COVID-19.

“With the recent increase in levels of COVID-19 circulating in the U.S., the risk to vulnerable individuals persists, including for those with hepatic impairment,” said Frank Duff, MD, Senior Vice President, Virology Therapeutic Area Head at Gilead Sciences. “This approval demonstrates Gilead’s ongoing commitment to COVID-19, including our focus on vulnerable populations.”

“The update to the safety profile and dosing recommendations for Veklury for those living with liver disease is important to this vulnerable population who faces an increased risk of complications from COVID-19,” said Douglas Dieterich, MD, Director, Institute for Liver Medicine, Professor of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai. “While COVID-19 is no longer a public health emergency, the virus continues to present a threat to those with underlying conditions.”

This approval follows the recent FDA and European Commission decisions to extend the approved use of Veklury to treat COVID-19 in people with severe renal impairment, including those on dialysis.

Gilead’s ongoing research in the most vulnerable patient populations with high unmet need is a testament to the company’s commitment to COVID-19 and this approval further validates Veklury’s overall safety profile.

About GS-US-540-9014

Gilead conducted a Phase 1, multicenter, open-label, single-dose study to evaluate the pharmacokinetics (PK) of Veklury and its metabolites in participants with normal hepatic function and moderate or severe hepatic impairment. Participants with varying degrees of hepatic impairment and normal hepatic function were enrolled as follows: Cohort 1: 20 participants (10 moderate hepatic impairment and 10 matched normal hepatic function control participants, for a target of 8 evaluable per group) Cohort 2: 12 participants (6 severe hepatic impairment and 6 matched normal hepatic function control participants).

About Gilead’s COVID-19 Development Program

Veklury (remdesivir) is a nucleotide analog prodrug invented and developed by Gilead, building on more than a decade of the company’s research on broad-spectrum antivirals for emerging viruses. Veklury is the antiviral standard of care for the treatment of hospitalized patients with COVID-19 and is a recommended treatment for 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.

Veklury directly inhibits viral replication inside of the cell by targeting the SARS-CoV-2 viral RNA polymerase. Based on in vitro analyses, Veklury retains antiviral activity against recent Omicron subvariants of concern, including XBB, XBB.1.5 and CH.1.1. Veklury continues to be evaluated against emerging variants of interest and concern, including EG.5, EG.5.1 and BA.2.86.

Veklury is approved in more than 50 countries worldwide. To date, Veklury and generic remdesivir have been made available to more than 13 million patients around the world, including more than 8 million people in middle- and low-income countries through Gilead’s voluntary licensing program.

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 antiviral, obeldesivir, for the treatment of COVID-19. Obeldesivir is a direct-acting nucleoside inhibitor of the of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), a critical component that the virus uses to replicate. Once metabolized, obeldesivir works in the same way as Veklury to halt SARS-CoV-2 virus replication.

U.S. Indication for Veklury

Veklury^® (remdesivir 100 mg for injection) 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 and 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

Contraindication

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.

Adverse reactions

• 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 interactions

• 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.
• Treatment duration:
  • 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 hepatic laboratory, and prothrombin time testing prior to initiating Veklury and during use as clinically appropriate.
  • Renal impairment: No dose adjustment of Veklury is recommended in patients with any degree of renal impairment, including patients on dialysis. Veklury may be administered without regard to the timing of dialysis.

Pregnancy and lactation

• Pregnancy: A pregnancy registry has been established for Veklury. Available clinical trial data for Veklury in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes following second- and third-trimester exposure. There are insufficient data to evaluate the risk of Veklury exposure during the first trimester. Maternal and fetal risks are associated with untreated COVID-19 in pregnancy.
• Lactation: Veklury can pass into breast milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Veklury and any potential adverse effects on the breastfed child from Veklury or from an underlying maternal condition. 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, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

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 effectively manage the supply and distribution of Veklury; 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 investigational treatments in its COVID-19 development program, 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; the risk that physicians may not see the benefits of prescribing Veklury; 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, 2023, 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.