FDA Approves PREZISTA®/ritonavir Once-Daily Dosing for HIV-1 Treatment-Experienced Adults With No Darunavir Resistance-Associated Mutations

December 13, 2010

TITUSVILLE, N.J., Dec. 13, 2010 /PRNewswire/ — Tibotec Therapeutics, a division of Centocor Ortho Biotech Products, L.P., announced today that the U.S. Food and Drug Administration (FDA) has approved a revision to the dosing recommendation to include once-daily dosing of PREZISTA® (darunavir) tablets in combination with ritonavir for the treatment of human immunodeficiency virus (HIV-1) in treatment-experienced adult patients with no darunavir resistance-associated mutations (DRV RAMs).(1)

The revised dosing recommendation extends the same dosing already approved for treatment-naive patients – PREZISTA, co-administered with ritonavir (in combination with other antiretroviral agents and with food, once-daily (800/100 mg) – to treatment-experienced patients with no DRV RAMs. The previously approved dosing recommendation for PREZISTA/ritonavir in treatment-experienced patients (patients who have taken HIV medications in the past) was PREZISTA/ritonavir 600/100 mg twice daily.

For antiretroviral treatment-experienced patients, genotypic testing is recommended. However, when genotypic testing is not feasible, PREZISTA/ritonavir 600/100 mg twice daily dosing is recommended.

The approval of this revision is based on 48-week data from the ODIN (Once-daily Darunavir In treatment-experieNced patients) study. ODIN evaluated the efficacy and safety of PREZISTA/ritonavir once daily vs. PREZISTA/ritonavir twice daily for the treatment of HIV-1 in treatment-experienced adult patients with no DRV RAMs (i.e., V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V, or L89V).

“With this once-daily dosing recommendation, boosted PREZISTA is now a viable option for more treatment-experienced patients,” said Glenn Mattes, president, Tibotec Therapeutics. “This approval reflects Tibotec’s ongoing commitment to optimizing dosing strategies for HIV patients.”

Data from the Phase 3b ODIN study were presented earlier this year at CROI 2010, the 17th Conference on Retroviruses and Opportunistic Infections, in San Francisco. The study achieved its primary objective of demonstrating non-inferiority of PREZISTA/ritonavir once daily compared with twice daily.

PREZISTA Indication: Adults

PREZISTA, co-administered with ritonavir and with other antiretroviral agents, is indicated for the treatment of HIV-1 infection.

This indication is based on analyses of plasma HIV-1 RNA levels and CD4+ cell counts from two controlled, Phase 3 trials of 48 weeks duration in antiretroviral treatment-naïve and treatment-experienced patients, and two controlled, Phase 2 trials of 96 weeks duration in clinically advanced, treatment-experienced adult patients.

    In treatment-experienced adult patients, the following points should be
     considered when initiating therapy with PREZISTA/ritonavir:
    -- Treatment history and, when available, genotypic or phenotypic
        testing, should guide the use of PREZISTA/ritonavir.
    -- The use of other active agents with PREZISTA/ritonavir is associated with a
        greater likelihood of treatment response.

About the ODIN Study

ODIN is a Phase 3b, randomized, open-label study that compared the efficacy, safety, and tolerability of PREZISTA/ritonavir 800/100 mg once daily versus PREZISTA/ritonavir 600/100 mg twice daily at week 48 in 590 treatment-experienced HIV-1-infected adult patients with no DRV RAMs (V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, L89V). Patients had HIV-1 RNA greater than 1,000 copies/mL and CD4 count greater than 50 cells/mm(3), and received a stable antiretroviral therapy regimen for greater than or equal to 12 weeks at screening. Patients received either once-daily (n=294) or twice-daily (n=296) PREZISTA/ritonavir plus optimized background regimen. The primary objective of the study was to demonstrate non-inferiority of PREZISTA/ritonavir 800/100 mg once daily versus PREZISTA/ritonavir 600/100 mg twice daily in confirmed virologic response (HIV-1 RNA less than 50 copies/mL [intent-to-treat/time-to-loss of virologic response; ITT-TLOVR]) at Week 48.

Important Safety Information

PREZISTA does not cure HIV-1 infection or AIDS, and does not prevent passing HIV-1 to others.

    Drug Interactions
    -- Coadministration of PREZISTA/ritonavir is
     contraindicated with drugs that are highly dependent on CYP3A
     for clearance and for which elevated plasma concentrations
     are associated with serious and/or life-threatening events
     (e.g., alfuzosin, dihydroergotamine, ergonovine, ergotamine,
     methylergonovine, cisapride, pimozide, oral midazolam,
     triazolam, lovastatin, or simvastatin)
    --Coadministration of PREZISTA/ritonavir is also
     contraindicated with rifampin and products containing St.
     John's wort (Hypericum perforatum) because this may cause
     significant decrease in plasma concentration of darunavir,
     resulting in loss of therapeutic effect and development of
    --Coadministration is not recommended with indinavir,
     lopinavir/ritonavir, saquinavir, and pravastatin
    --Caution should be used when prescribing agents such as
     sildenafil, vardenafil, tadalafil, or other substrates,
     inhibitors, or inducers of CYP3A in patients receiving
    -- This list of potential drug interactions is not complete.

    Warnings & Precautions
    --PREZISTA must be coadministered with ritonavir and food to
     achieve the desired antiviral effect. Failure to administer
     PREZISTA with ritonavir and food may result in a loss of
     efficacy of darunavir. Please refer to ritonavir prescribing
     information for additional information on precautionary
    -- Drug-induced hepatitis (e.g., acute hepatitis, cytolytic
     hepatitis) has been reported with PREZISTA/ritonavir. During
     the clinical development program (N=3063), hepatitis has been
     reported in 0.5% of patients receiving combination therapy
     with PREZISTA/ritonavir. Patients with preexisting liver
     dysfunction, including chronic active hepatitis B or C, have
     an increased risk for liver function abnormalities, including
     severe hepatic adverse events

           Post-marketing cases of liver injury, including some
            fatalities, have been reported. A causal relationship with
            PREZISTA/ritonavir therapy has not been established

           Appropriate laboratory testing should be conducted prior to
            initiating therapy with PREZISTA/ritonavir and patients
            should be monitored during treatment. Increased AST/ALT
            monitoring should be considered in patients with underlying
            chronic hepatitis, cirrhosis, or in patients who have
            pretreatment elevations of transaminases, especially during
            the first several months of PREZISTA/ritonavir treatment.
            Evidence of new or worsening liver dysfunction (including
            clinically significant elevation of liver enzymes and/or
            symptoms such as fatigue, anorexia, nausea, jaundice, dark
            urine, liver tenderness, hepatomegaly) in patients on
            PREZISTA/ritonavir should prompt consideration of
            interruption or discontinuation of treatment

    -- Severe Skin Reactions:  Severe skin reactions (0.4%),
     accompanied by fever and/or elevations of transaminases in
     some cases, Stevens-Johnson Syndrome (<0.1%), and toxic
     epidermal necrolysis (post-marketing experience) have been
     reported in patients receiving PREZISTA/ritonavir.
     Discontinue PREZISTA/ritonavir immediately if signs or
     symptoms of severe skin reactions develop (including, but not
     limited to, severe rash or rash accompanied with fever,
     general malaise, fatigue, muscle or join aches, blisters,
     oral lesions, conjunctivitis, hepatitis and/or eosinophilia)

    In clinical trials (N=3063), rash (all grades, generally mild
     to moderate, regardless of causality) occurred in 10.3% of
     patients receiving PREZISTA/ritonavir. Discontinuation due
     to rash was 0.5%
    --Sulfa Allergy: PREZISTA should be used with caution in
     patients with known sulfonamide allergy
    -- Diabetes Mellitus/Hyperglycemia and Hemophilia: New-
     onset or exacerbations of preexisting diabetes mellitus,
     hyperglycemia, and increased bleeding in hemophiliacs have
     been reported in patients receiving protease inhibitors.
     Initiation or dose adjustments of insulin or oral
     hypoglycemic agents may be required. A causal relationship
     between protease inhibitors and these events has not been
    -- Fat Redistribution: Redistribution and/or accumulation
     of body fat have been observed in patients receiving ARV
     therapy. The causal relationship, mechanism, and long-term
     consequences of these events have not been established
    --Immune reconstitution syndrome has been reported in
     patients treated with ARV therapy
    -- Resistance/Cross Resistance: The potential for HIV-1
     cross-resistance among protease inhibitors has not been
     fully explored in PREZISTA/ritonavir-treated patients

    Use in Specific Populations
    --Hepatic Impairment: PREZISTA/ritonavir is not recommended
     for use in patients with severe hepatic impairment. There are
     no pharmacokinetic or safety data available in patients with
     severe hepatic impairment
    -- Pregnancy: PREZISTA should be used during pregnancy only
     if the potential benefit justifies the potential risk. No
     adequate and well-controlled studies have been conducted in
     pregnant women

    Adverse Reactions
    -- In treatment-naïve adult patients, the most common
     adverse drug reactions (greater than or equal to 5%) reported
     of at least moderate intensity (greater than or equal to
     Grade 2) in the PREZISTA/ritonavir arm through 96 weeks were
     diarrhea (8%), headache (6%), abdominal pain (5%), and rash
    -- In treatment-experienced adult patients, the most common
     adverse drug reactions (greater than or equal to 5%) reported
     of at least moderate intensity (greater than or equal to
     Grade 2) in the PREZISTA/ritonavir arm through 96 weeks were
     diarrhea (14%), nausea (7%), rash (7%), abdominal pain (6%),
     and vomiting (5%)

This is not a complete list of all adverse drug reactions reported with the use of PREZISTA/ritonavir.

Please see accompanying full Prescribing Information for more details. Full prescribing information is also available at www.PREZISTA.com.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

About Tibotec Pharmaceuticals

Tibotec Pharmaceuticals, based in Cork, Ireland, is a pharmaceutical research and development company. The Company’s main research and development facilities are in Beerse, Belgium, with offices in Titusville, NJ, USA. Tibotec is dedicated to the discovery and development of innovative HIV-1/AIDS drugs and anti-infectives for diseases of high unmet medical need.

About Tibotec Therapeutics

Tibotec Therapeutics, a division of Centocor Ortho Biotech Products, L.P., headquartered in Titusville, NJ, is dedicated to delivering innovative virology therapeutics that help healthcare professionals address serious unmet needs in people living with HIV-1.

(1) Resistance-associated mutations are also referred to as resistance-associated substitutions.

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SOURCE Tibotec Therapeutics

Source: newswire

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