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Gilead Sciences, Inc.

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John C. Martin, PhD, Chairman and CEO, commented on the regulatory status of the single-tablet regimen of Elvitegravir, Cobicistat, Emtricitabine and TAF abbreviated E/C/F/TAF in the USand EU. He stated, "In HIV, regulatory submissions for our first TAF contained product, the single-tablet regimen of Elvitegravir, Cobicistat, Emtricitabine and TAF abbreviated E/C/F/TAF have been submitted in the EU, and the U.S. The application was validated in the EU and in the U.S. it will undergo standard review with an anticipated FDA action date of November 5th."
Source: Q4 2014 earnings conference call, 2/03/15.

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Gilead Submits New Drug Application to U.S. Food and Drug Administration for Tenofovir Alafenamide (TAF)-Based Single Tablet Regimen for HIV
– High Rates of Viral Suppression and Improved Renal and Bone Safety Demonstrated in Phase 3 Studies –

– First of Several TAF-Based Single Tablet Regimens Being Evaluated by Gilead –

FOSTER CITY, Calif.--(BUSINESS WIRE)--Nov. 6, 2014-- Gilead Sciences, Inc. (NASDAQ: GILD) today announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for an investigational, once-daily single tablet regimen containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg and tenofovir alafenamide (TAF) 10 mg (E/C/F/TAF) for the treatment of HIV-1 infection in adults. The data submitted in the NDA support the use of the regimen among adult and adolescent treatment-naïve HIV individuals, virologically suppressed patients who switch regimens and those with renal impairment. If approved, E/C/F/TAF would be Gilead’s first single tablet regimen to contain TAF.

TAF is an investigational, novel prodrug of tenofovir, the active agent in Gilead’s Viread® (tenofovir disoproxil fumarate). TAF is a more targeted form of tenofovir than Viread that has demonstrated high antiviral efficacy at a dose that is 10 times lower, as well as an improved renal and bone safety profile.

“This TAF-based regimen has the potential to provide a range of HIV patients with a highly effective and well-tolerated new treatment option with a favorable safety profile,” said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. “Gilead remains focused on advancing next-generation therapies that have the potential to improve HIV treatment over the long-term and TAF will be the cornerstone of future Gilead single tablet regimens.”

The NDA for E/C/F/TAF is supported by 48-week data from two pivotal Phase 3 studies (Studies 104 and 111) in which the regimen met its primary objective of non-inferiority compared to Gilead’s Stribild® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) among treatment-naïve patients. In the studies, E/C/F/TAF demonstrated improved renal and bone safety compared to Stribild. The NDA is also supported by data from additional Phase 3 studies evaluating the TAF-based regimen among virologically suppressed patients who switched to E/C/F/TAF and among patients with renal impairment. In addition, the filing is supported by Chemistry, Manufacturing and Controls (CMC) information on the individual components and the co-formulated single tablet regimen.

Gilead plans to submit a regulatory application for E/C/F/TAF in the European Union by the end of 2014.

TAF and TAF-based regimens are investigational products and have not been determined safe or efficacious.
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Source: press release, 11/06/14. http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=...

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Compound/DeviceSpecialtyIndicationCompound ClassTarget
Elvitegravir/Cobicistat/Emtricitabine/TAF combination (E/C/F/TAF)Infectious DiseaseHuman Immunodeficiency Virus (HIV)Combination therapy (antiretroviral)Various HIV

Mechanism of action: Elvitegravir (GS-9137), a SM-inhibitor, interferes with the transfer of the viral genome into the host genome via inhibition of the integrase enzyme. Cobicistat (GS-9350)is a pharmacokinetic enhancer, is a potent mechanism-based inhibitor of cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body. Tenofovir alafenamide (TAF) (GS-7340), a SM, nucleotide analogue reverse transcriptase inhibitor (nRTI). Emtricitabine is a small molecules that inhibit the transcription of viral RNA into DNA by acting as a nucleotide analogue reverse transcriptase inhibitor (nRTI). Tenofovir alafenamide inhibits the transcription of viral RNA into DNA. It is a novel prodrug of tenofovir.

Phase of Development: Filed

Event Type: Regulatory FDA: PDUFA DATE

Dates: 2015-11-05

Results:

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U.S. Food and Drug Administration Approves Gilead’s Single Tablet Regimen Genvoya® (Elvitegravir, Cobicistat, Emtricitabine and Tenofovir Alafenamide) for Treatment of HIV-1 Infection
– Gilead’s First TAF-based Regimen Demonstrates High Efficacy with Improved Renal and Bone Parameters Compared to TDF-based Regimens –

FOSTER CITY, Calif.--(BUSINESS WIRE)--Nov. 5, 2015-- Gilead Sciences, Inc. (NASDAQ:GILD) announced today that the U.S. Food and Drug Administration (FDA) has approved Genvoya® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg or E/C/F/TAF) for the treatment of HIV-1 infection. Genvoya is the first TAF-based regimen to receive FDA approval.

Genvoya is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older who have no antiretroviral treatment history or to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA levels less than 50 copies per mL) on a stable antiretroviral regimen for at least six months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Genvoya. No dosage adjustment of Genvoya is required in patients with estimated creatinine clearance greater than or equal to 30 mL per minute.

Genvoya has a boxed warning in its product label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis, and post treatment acute exacerbation of hepatitis B. Further important safety information, adverse drug reactions and drug interactions are listed below.

Photos and multimedia gallery available at www.GileadHIVMedia.com.

TAF is a novel targeted prodrug of tenofovir that has demonstrated high antiviral efficacy similar to and at a dose less than one-tenth that of Gilead’s Viread® (tenofovir disoproxil fumarate, TDF), as well as improvement in surrogate laboratory markers of renal and bone safety as compared to TDF in clinical trials in combination with other antiretroviral agents. Data show that because TAF enters cells, including HIV-infected cells, more efficiently than TDF, it can be given at a lower dose and there is 91 percent less tenofovir in the bloodstream.

“As the HIV patient population ages there is an increased risk for development of age- and treatment-related comorbidities, including low bone mineral density and renal impairment. This is due to the combination of HIV infection, antiretroviral treatments and the natural aging process,” said David Wohl, MD, Associate Professor of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill and lead author of the Genvoya efficacy analysis. “Given its demonstrated efficacy and safety profile, Genvoya represents an important new treatment option for a range of patients who are either new to therapy or who choose to switch treatments.”

Genvoya was studied in a Phase 3 HIV clinical program in more than 3,500 patients across 21 countries, including treatment-naïve, virologically suppressed, renally impaired and adolescent patients. The approval is supported by 48-week data from two Phase 3 double-blind studies (Studies 104 and 111) among 1,733 treatment-naïve patients in which the regimen met its primary objective of non-inferiority compared to Stribild® (elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg or E/C/F/TDF). In the combined analysis of the studies, 92.4 percent of Genvoya patients and 90.4 percent of Stribild patients had HIV-1 RNA levels less than 50 copies/mL at Week 48. Tests of certain renal and bone laboratory parameters also favored Genvoya over Stribild.

Additionally, the approval is supported by a Phase 3 study (Study 109) evaluating Genvoya among virologically suppressed patients who switched from TDF-based regimens. The study enrolled 1,436 subjects and 1,196 had reached the 48-week time point at the time of filing. Among those patients, Genvoya was found to be statistically non-inferior to the TDF-based regimens based on the percentages of patients with HIV-1 RNA levels less than 50 copies/mL at Week 48. Patients receiving Genvoya also demonstrated improvements in certain bone and renal laboratory parameters compared to those treated with the TDF-based regimens. Finally, data from Phase 3 studies evaluating Genvoya among adolescents and patients with mild-to-moderate renal impairment supported the approval.

“While exceptional progress has been made in the field of HIV, there is still a need for new treatment options that may help improve the health of people as they grow older with the disease,” said John C. Martin, PhD, Chairman and Chief Executive Officer, Gilead Sciences. “For more than 25 years, Gilead has been committed to changing the trajectory of HIV management and we are now pleased to introduce Genvoya, the first in a portfolio of TAF-based products that have the potential to advance the long-term treatment of HIV.”

Two other TAF-based regimens are currently under evaluation by the FDA. The first is an investigational, fixed-dose combination of emtricitabine 200 mg and tenofovir alafenamide 25 or 10 mg (F/TAF) for use in combination with other antiretroviral agents. The second is an investigational, once-daily single tablet regimen that combines emtricitabine 200 mg, tenofovir alafenamide 25 mg and rilpivirine 25 mg (R/F/TAF). Emtricitabine and tenofovir alafenamide are from Gilead and rilpivirine is from Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson.

F/TAF and R/F/TAF are investigational products and have not been determined to be safe or efficacious.

Genvoya does not cure HIV infection or AIDS.
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Source: press release, 11/05/15. http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=...

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