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DHHS Updates Antiretroviral Treatment Guidelines for Adults and Children

The U.S. Department of Health and Human Services (DHHS) has released updated versions of its antiretroviral treatment guidelines for adults and adolescents, and for children with HIV. The new adult guidelines include revised recommendations for first-line antiretroviral therapy (ART) as well as management of treatment-experienced patients. The revised pediatric guidelines include a discussion of very early treatment for HIV-infected infants.

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Gilead Requests Approval of Tenofovir Alafenamide Dual Combination Pill

Gilead Sciences has requested U.S. Food and Drug Administration approval of a combination pill containing emtricitabine plus tenofovir alafenamide (TAF), a new formulation that is easier on the kidneys and bones, according to a company press release. If approved, the new coformulation could take the place of Truvada for HIV treatment, though its effectiveness for pre-exposure prophylaxis, or PrEP, is not yet known.

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Tenofovir disoproxil fumarate or TDF (Viread, also in Truvada, Atripla, and other Gilead single-tablet regimens) is one of the most widely used antiretroviral drugs. TAF is a pro-drug that delivers the active agent to HIV-infected cells more efficiently than TDF. TAF produces adequate intracellular drug levels with lower doses, which means lower concentrations in the blood plasma and less drug exposure for organs and tissues.

As reported at the recent 2015 Conference on Retroviruses and Opportunistic infections, Phase 3 studies have shownthat a single-tablet regimen containing TAF, emtricitabine, elvitegravir, and cobicistat was equally effective at suppressing HIV but hadless detrimental effects on the kidneys and bones than the existing Stribild coformulation containing TDF.

Below is an edited excerpt from a Gilead press release describing the TAF/emtricitabine new drug application. The company has also requested approval of the 4-drug single-tablet regimen described above, and stand-alone TAF is being developed as a treatment for hepatitis B.

Gilead Submits New Drug Application to U.S. Food and Drug Administration for Fixed-dose Combination of Emtricitabine/Tenofovir Alafenamide for HIV Treatment

Potential New Backbone for Future HIV Therapy Combinations

Foster City, Calif. -- April 7, 2015 -- 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 two doses of an investigational fixed-dose combination of emtricitabine and tenofovir alafenamide (200/10 mg and 200/25 mg) (F/TAF) for the treatment of HIV-1 infection in adults and pediatric patients age 12 years and older, in combination with other HIV antiretroviral agents.

TAF is a novel nucleotide reverse transcriptase inhibitor(NRTI) that has demonstrated high antiviral efficacy at a dose less than one-tenth that of Gilead’s Viread (tenofovir disoproxil fumarate, TDF), as well as improved renal and bone laboratory parameters as compared to TDF in clinical trials.

"Gilead has a long history of innovating HIV treatments, and with F/TAF we have the potential to further optimize therapies for HIV patients who face a lifetime of antiretroviral treatment," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. "With its high antiviral efficacy and favorable safety profile, F/TAF may offer an improved backbone for a new generation of HIV regimens."

Today’s filing is Gilead’s second F/TAF-based NDA submitted to the FDA for review.  In November 2014, Gilead filed an NDA for an investigational once-daily single tablet regimen containing elvitegravir 150 mg, cobicistat 150 mg, emtricitabine 200 mg, and TAF 10 mg (E/C/F/TAF). Under the Prescription Drug User Fee Act, the FDA has set a target action date of November 5, 2015. Additionally, a Marketing Authorization Application in the European Union for E/C/F/TAF was fully validated on December 23, 2014.

The F/TAF NDA is supported by data from Phase 3 clinical studies evaluating the safety and efficacy of E/C/F/TAF for the treatment of HIV-1 infection among treatment-naive adults, in which the F/TAF-based regimen (administered as E/C/F/TAF) resulted in non-inferior efficacy and improved renal and bone laboratory parameters as compared to F/TDF-based therapy (administered as E/C/F/TDF or Stribild).The NDA is also supported by data from additional Phase 3 studies evaluating the F/TAF-based regimen (administered as E/C/F/TAF) among treatment-naive adolescents, virologically suppressed adults who switched regimens, and adults with mild-to-moderate renal impairment. Lastly,bioequivalence studies demonstrated that the formulation of the fixed-dose combinations of F/TAF achieved the samedruglevelsin the blood as in E/C/F/TAF.

The recommended dose of F/TAF is 200/25 mg; if it is used in combination with a protease inhibitor that is administered with either ritonavir or cobicistat, the recommended dose is 200/10 mg.

Additional F/TAF-based regimens for HIV treatment are currently in development. In December 2014, Gilead announced the expansion of its existing agreements with Janssen Sciences Ireland UC for the development and commercialization of two new investigational once-daily single tablet regimens containing F/TAF. One combines F/TAF with Janssen’s rilpivirine. The other regimen contains F/TAF, cobicistat and Janssen’s darunavir.

Gilead plans to submit a regulatory application for F/TAF in the European Union in the second quarter of 2015.

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

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need.  The company’s mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

4/8/15

Source

Gilead Sciences. Gilead Submits New Drug Application to U.S. Food and Drug Administration for Fixed-dose Combination of Emtricitabine/Tenofovir Alafenamide for HIV Treatment. Press release. April 7, 2014.

CROI 2015: Does Emtricitabine Work Better than Lamivudine in Combination ART?

People with HIV who started an antiretroviral regimen containing emtricitabine (FTC; Emtriva) and NNRTIs were about half as likely to experience virological treatment failure as those who used the similar drug lamivudine (3TC; Epivir), according to an analysis of more than 6000 participants in the Dutch ATHENA cohort presented at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. No significant differences between emtricitabine and lamivudine were seen with boosted protease inhibitor regimens.

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Trial of CCR5-Deleted Stem Cell Gene Therapy for HIV Gets FDA Go-Ahead

The U.S. Food and Drug Administration (FDA) has given approval to proceed with a clinical trial of a gene therapy method that cuts the gene for the CCR5 coreceptor out of stem cells, making them resistant to HIV entry, the California Institute for Regenerative Medicine (CIRM) recently announced.

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CROI 2015: Researchers Discuss HIV Cure Strategies

Researchers at the recent 2015 Conference on Retroviruses and Opportunistic Infections in Seattle discussed a variety of approaches to achieve a functional cure, or prolonged remission of HIV. Most experts expect that a combination of multiple approaches will be needed.

Early Antiretroviral Treatment Reduces, but Does Not Eliminate HIV Reservoir

Experimental Agents Reverse HIV Latency, Help Immune System Fight Infected Cells

We May Need to Combine Many Approaches to Achieve a Cure for HIV

3/20/15

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CROI 2015: Experimental Agents Reverse HIV Latency, Help Immune System Fight Infected Cells

Researchers at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle presented data on several experimental agents that may play a role in achieving a "functional cure" for HIV, or prolonged remission without disease progression. These include drugs that reactivate the latent HIV reservoir, interfere with expression of viral DNA, and help the immune system target HIV-infected cells.

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CROI 2015: Early Antiretroviral Treatment Reduces, but Does Not Eliminate HIV Reservoir

Starting antiretroviral therapy (ART) very soon after infection may limit the size of the HIV reservoir and delay viral rebound after treatment interruption, according to several presentations at the recent 2015 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle. Other research showed that various biomarkers may predict who will experience HIV rebound after stopping ART.

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