Veklury® (remdesivir) efficacy and safety profile further demonstrated in vulnerable patient populations

– 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) –

FOSTER CITY, Calif., April 16, 2023 — 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.

Read the full press release here.

SEE ALSO:

• Infectious Disease Special Edition: Remdesivir reduces readmission risk by 16% among immunocompromised patients with COVID-19