Gilead Sciences, Inc. (Nasdaq: GILD) announced today that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Veklury® (remdesivir), an investigational antiviral for the treatment of patients with COVID-19. Veklury is currently available in the U.S. under an Emergency Use Authorization (EUA) for the treatment of hospitalized patients with severe COVID-19. The filing is the final tier of the rolling NDA submission that was initiated on April 8, 2020. TrialSite reminds readers that the company was afforded the condition to generate from $1 billion to $3 billion in revenues under the provisional FDA EUA status—an unprecedented achievement due to a confluence of factors and forces from the pandemic itself to the sponsor’s controversial move to actually change the critical endpoint measure of a Phase 3 clinical trial. Pricing has evolved into an interesting topic with the U.S. private payer shelling out nearly 50 times the amount as India payers, during pandemic conditions.
Controversial Move on Part of Sponsors
In an unprecedented move, government clinical trial investigators modified the clinical trial’s primary endpoint measure just two weeks before Anthony S. Fauci’s announcement that the drug would be a new “standard of care.” Christopher Roland of the Washington Post told the world of the critically important measure associated with the efficacy of the drug: a reduction in COVID-19 deaths would be controversially swapped out for recovery time, which turned out to be a reduction in hospitalization days from 15 down to 11. Dr. Fauci would conclude this was no “knock out drug.”
Drug Blockbuster Despite only Having EUA Status
But what wouldn’t matter. With a raging pandemic and a fresh EUA with a seal of approval from perhaps the most influential physician/researcher in the world—Dr. Fauci—a “new standard of care” for COVID-19 triggers massive demand for the product. So much so that recently TrialSite reported top analysts were forecasting revenue in the first 12 months for the EUA-status product of between $1 billion and $3 billion. Thus, Veklury enters “Blockbuster” territory. Although TrialSite agrees with Gilead that it priced this product rationally as per ICER suggested ranges, a core underlying assumption in the ICER pricing analysis for Remdesivir: that the drug actually reduce the death rate. Presently, evidence from randomized trials doesn’t support this claim. However, there is some observational data (e.g. Real World Evidence) that Remdesivir might positively impact death rates for at least some patients but this of course cannot be used for any claims for marketing authorization.
Evidence Supporting the Filing
The filing is supported by data from two randomized, open-label, multi-center Phase 3 clinical studies of Veklury conducted by Gilead and the Phase 3 randomized, placebo-controlled study of Veklury conducted by the National Institute of Allergy and Infectious Diseases (NIAID). These studies demonstrated that treatment with Veklury led to faster time to recovery compared with placebo and that a 5-day or 10-day treatment duration led to similar clinical improvement. Across studies, Veklury was generally well-tolerated in both the 5-day and 10-day treatment groups, with no new safety signals identified.
Highlighting the company’s relentless efforts during the pandemic, Chief Medical Officer Merdad Parsey, MD, PhD, commented, “Since the beginning of the pandemic, Gilead has worked with urgency to establish the efficacy and safety profile of Veklury, and we now have a robust data set supporting the evaluation of use of the drug across a range of hospitalized COVID-19 patient populations.” The Chief Medical Officer informed, “Today’s filing is an important milestone as we continue to partner with the U.S. government and healthcare authorities around the globe to address the treatment needs of patients with COVID-19.”
One Year Conditional Approval in Europe
Veklury has been approved by multiple regulatory authorities around the world, including in the European Union and Japan. Specifically, by July, in Europe the product received a one year conditional marketing authorization. With not the strongest data, the European authority offered the authorization due to the COVID-19 pandemic and the lack of any other approved treatments.
Japan’s approval came days after the early May EUA authorization by the U.S. Food and Drug Administration. In Australia, by July 10 the Australian Therapeutic Goods Administration (TGA) granted provisional approval status to remdesivir (Veklury) as a treatment option for COVID-19. Importantly, the company was awarded provisional approval for use in adults and adolescent patients with severe COVID-19 symptoms who have been hospitalized. This grant came about because it was the only drug to offer some proven efficacy for those suffering from SARS-CoV-2 infection. The Australian TGA noted, “While this is a major milestone in Australia’s struggle against the pandemic, it is important to emphasize that the product has not been shown to prevent coronavirus infection or relieve milder cases of infection.”
By July 28, 2020, Health Canada issued a conditional authorization, similar to Europe, and with conditions including 1) post-market safety monitoring reports as well as reports on all serious adverse drug reactions; 2) ongoing supply of safety and efficacy data from clinical trials and patients; and 3) additional quality data as to adherence to GmP, etc.
India Approved as DESREM®
In India, the drug would be approved by the authority there—the Drug Controller General of India (DCGI)—under a contract with generic producer Mylan. The drug was approved under the brand name DESREM® and available at 4,800 Indian Rupees or $64.29 for a course of treatment, making the price to U.S. government payers 36 times as high ($2,340 per course for U.S. government payers such as Medicare and Medicaid). Private insurers in the U.S. would pay nearly 50 times the amount charged in India ($3,120).
Gilead entered into a licensing deal with Mylan to distribute the product in up to 127 low- and middle-income countries.
Veklury (remdesivir) is an investigational nucleotide analog with broad-spectrum antiviral activity both in vitro and in vivo in animal models against multiple emerging viral pathogens. Multiple ongoing international Phase 3 clinical trials are evaluating the safety and efficacy of Veklury for the treatment of SARS-CoV-2 infection, the virus that causes COVID-19, in different patient populations, formulations, and in combination with other therapies.
Important Information about Veklury in the United States
In the United States, Veklury (remdesivir) is authorized for use under an Emergency Use Authorization (EUA) only for the treatment of patients with suspected or laboratory-confirmed SARS-CoV-2 infection and severe COVID-19. Severe disease is defined as patients with an oxygen saturation (SpO2) ≤ 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). Veklury must be administered via intravenous (IV) infusion and is supplied two ways: Veklury (remdesivir) for injection, 100 mg, lyophilized powder, or Veklury (remdesivir) injection, 100 mg/20 mL (5 mg/mL), concentrated solution.
An Investigational Drug
Veklury is an investigational drug that has not been approved by the FDA for any use, and the safety and efficacy of Veklury for the treatment of COVID-19 have not been established. This authorization is temporary and may be revoked, and does not take the place of the formal new drug application submission, review and approval process. For information about the authorized use of Veklury and mandatory requirements of the EUA in the U.S., please review the Fact Sheets and FDA Letter of Authorization available here.
There are limited clinical data available for Veklury. Serious and unexpected adverse events may occur that have not been previously reported with Veklury use. Hypersensitivity reactions, including infusion-related and anaphylactic reactions, have been observed during and following administration of Veklury. The use of Veklury is contraindicated in patients with known hypersensitivity to remdesivir. Transaminase elevations have been observed in healthy volunteers and patients with COVID-19 in clinical trials who received Veklury. Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. Monitor renal and hepatic function prior to initiating and daily during therapy with Veklury; additionally monitor serum chemistries and hematology daily during therapy. Do not initiate Veklury in patients with ALT ≥5x ULN or with an eGFR <30 mL/min. The decision to continue or discontinue Veklury therapy after development of an adverse event should be made based on the clinical risk/benefit assessment for the individual patient.
Due to a risk of reduced antiviral activity, coadministration of Veklury and chloroquine phosphate or hydroxychloroquine sulfate is not recommended.
Healthcare providers and/or their designee are responsible for mandatory FDA MedWatch reporting of all medication errors and serious adverse events or deaths occurring during Veklury treatment and considered to be potentially attributable to Veklury. These events must be reported within 7 calendar days from the onset of the event. MedWatch adverse event reports can be submitted to FDA online at www.fda.gov/medwatch or by calling 1-800-FDA-1088.