Triumeq (abacavir, dolutegravir and lamivudine) Product Backgrounder for US Media

Transcription

1 Triumeq (abacavir, dlutegravir and lamivudine) Prduct Backgrunder fr US Media What is Triumeq and wh is Triumeq fr? Triumeq (abacavir 600mg, dlutegravir 50mg and lamivudine 300mg) is the first dlutegravir-based fixed-dse cmbinatin, ffering many peple living with HIV the ptin f a single-pill regimen that cmbines the integrase strand transfer inhibitr (INSTI) dlutegravir, with the nucleside reverse transcriptase inhibitrs (NRTIs) abacavir and lamivudine. 1 Triumeq alne is nt recmmended fr use in patients with current r past histry f resistance t any cmpnents f Triumeq. Triumeq alne is nt recmmended in patients with resistance-assciated integrase substitutins r clinically suspected INSTI resistance because the dse f dlutegravir in Triumeq is insufficient in these ppulatins. Befre initiating treatment with abacavir-cntaining prducts, screening fr the presence f a genetic marker, the HLA-B*5701 allele, shuld be perfrmed in any HIV-infected patient, irrespective f racial rigin. Prducts cntaining abacavir shuld nt be used in patients knwn t carry the HLA-B*5701 allele. 1 Triumeq is cntraindicated in patients with a previus hypersensitivity reactin (HSR) t abacavir, dlutegravir r lamivudine. Hwever, HSR have been bserved mre cmmnly with abacavir, sme f which have been serius and in rare cases fatal. Clinically it is nt pssible t determine whether a HSR with Triumeq is caused by abacavir, dlutegravir r lamivudine. 1 Triumeq is a pill that can be taken with r withut fd and may be taken at any time f day. 1 Please refer t the US Prescribing Infrmatin fr full prduct infrmatin. 1 Hw des Triumeq wrk? Triumeq cntains the INSTI dlutegravir and the NRTIs abacavir and lamivudine. 1 Tw essential steps in the HIV life cycle are replicatin when the virus turns its RNA cpy int DNA and integratin the mment when viral DNA becmes part f the hst cell s DNA. 2,3 These prcesses require tw enzymes called reverse transcriptase and integrase. NRTIs and integrase inhibitrs interfere with the actin f the tw enzymes t prevent the virus frm replicating and further infecting cells. 2,3 What rle des Triumeq play in the treatment f HIV? Triumeq prvides many peple living with HIV the ptin f a single-pill regimen cntaining dlutegravir. Despite the widespread availability f drugs that target HIV,

2 bth in the US and the EU, nly between 52% and 58% f peple living with HIV are satisfied with the tlerability f their current regimen, signifying the cntinued need fr new treatment ptins fr peple living with HIV. 4,5 ViiV Healthcare is cmmitted t delivering advances in care and new treatment ptins t physicians and peple living with HIV. Althugh single-pill regimens have been available t peple living with HIV fr sme time, Triumeq is the first single-pill regimen cntaining dlutegravir. Which clinical trials supprted the apprval f Triumeq? The FDA apprval is based primarily upn data frm tw clinical trials: the Phase III study (SINGLE) f treatment-naïve adults, cnducted with dlutegravir and abacavir/lamivudine as separate pills 6,7 a biequivalence study f the fixed-dse cmbinatin f abacavir, dlutegravir and lamivudine when taken as a single pill cmpared t the administratin f dlutegravir and abacavir/lamivudine as separate pills. 8 In the SINGLE study, a nn-inferirity trial with a pre-specified superirity analysis, mre patients were undetectable (HIV-1 RNA <50 cpies/ml) in the dlutegravir and abacavir/lamivudine arm (the separate cmpnents f Triumeq) than in the Atripla (efavirenz, emtricitabine and tenfvir) arm, the mst cmmnly used single-pill regimen. The difference was statistically significant and met the pre-specified test fr superirity. The difference was driven by a higher rate f discntinuatin due t adverse events in the Atripla arm. 6,7 At 96 weeks, 80% f participants n the dlutegravir-based regimen were virlgically suppressed cmpared t 72% f participants n Atripla. Grade 2-4 treatment emergent adverse reactins ccurring in 2% r mre participants taking the dlutegravir-based regimen were insmnia (3%), headache (2%) and fatigue (2%). 7 The biequivalence study evaluated Triumeq (abacavir, dlutegravir and lamivudine) when taken as a single pill cmpared t the administratin f dlutegravir and abacavir/lamivudine as separate pills. The study was perfrmed accrding t the usual methds fr this type f study. 8 Biequivalence was demnstrated between the Triumeq single pill and the separate c-administered tablet frmulatins f dlutegravir and abacavir/lamivudine. 8 Additinally, the effect f fd n the plasma pharmackinetics f the single pill cmpnents, abacavir, dlutegravir and lamivudine, was similar t fd effects bserved with dlutegravir plus abacavir/lamivudine, indicating that the Triumeq single pill may be taken with r withut fd. 8

3 Imprtant Safety Infrmatin (ISI) fr Triumeq (abacavir, dlutegravir and lamivudine) tablets The fllwing ISI is based n the Highlights sectin f the Prescribing Infrmatin fr Triumeq. Please cnsult the full Prescribing Infrmatin fr all the labeled safety infrmatin fr Triumeq. BOXED WARNING: RISK OF HYPERSENSITIVITY REACTIONS, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY AND EXACERBATIONS OF HEPATITIS B See full Prescribing Infrmatin fr cmplete bxed warning. Serius and smetimes fatal hypersensitivity reactins have been assciated with abacavircntaining prducts. Hypersensitivity t abacavir is a multi-rgan clinical syndrme. Patients wh carry the HLA-B*5701 allele are at high risk fr experiencing a hypersensitivity reactin t abacavir. Discntinue Triumeq as sn as hypersensitivity reactin is suspected. Regardless f HLA- B*5701 status, permanently discntinue Triumeq if hypersensitivity cannt be ruled ut, even when ther diagnses are pssible. Fllwing a hypersensitivity reactin t abacavir, NEVER restart Triumeq r any ther abacavir-cntaining prduct. Lactic acidsis and severe hepatmegaly with steatsis, including fatal cases, have been reprted with the use f nucleside analgues. Severe acute exacerbatins f hepatitis B have been reprted in patients wh are cinfected with Hepatitis B Virus (HBV) and Human Immundeficiency Virus (HIV-1) and have discntinued lamivudine, a cmpnent f Triumeq. Mnitr hepatic functin clsely in these patients and, if apprpriate, initiate anti-hepatitis B treatment. CONTRAINDICATIONS Presence f HLA-B*5701 allele. Previus hypersensitivity reactin t abacavir, dlutegravir r lamivudine. C-administratin with dfetilide. Mderate r severe hepatic impairment. WARNINGS AND PRECAUTIONS Patients with underlying hepatitis B r C may be at increased risk fr wrsening r develpment f transaminase elevatins with use f Triumeq. Apprpriate labratry testing prir t initiating therapy and mnitring fr hepattxicity during therapy with Triumeq is recmmended in patients with underlying hepatic disease such as hepatitis B r C.

4 Hepatic decmpensatin, sme fatal, has ccurred in HIV-1/Hepatitis C Virus (HCV) cinfected patients receiving cmbinatin antiretrviral therapy and interfern alfa with r withut ribavirin. Discntinue Triumeq as medically apprpriate and cnsider dse reductin r discntinuatin f interfern alfa, ribavirin r bth. Immune recnstitutin syndrme and redistributin/accumulatin f bdy fat have been reprted in patients treated with cmbinatin antiretrviral therapy. Administratin f Triumeq is nt recmmended in patients receiving ther prducts cntaining abacavir r lamivudine. ADVERSE REACTIONS The mst cmmnly reprted ( 2%) adverse reactins f at least mderate intensity in treatmentnaïve adult subjects receiving Triumeq were insmnia (3%), headache (2%) and fatigue (2%). DRUG INTERACTIONS C-administratin f Triumeq with ther drugs can alter the cncentratin f ther drugs, and ther drugs may alter the cncentratins f Triumeq. The ptential drug-drug interactins must be cnsidered prir t and during therapy. USE IN SPECIFIC POPULATIONS Pregnancy: Triumeq shuld be used during pregnancy nly if the ptential benefit justifies the ptential risk. Nursing mthers: Breastfeeding is nt recmmended due t the ptential fr HIV transmissin. Triumeq is nt recmmended in patients with creatinine clearance f less than 50 ml per min. If a dse reductin f abacavir, a cmpnent f Triumeq, is required fr patients with mild hepatic impairment, then the individual cmpnents shuld be used. Cntact Infrmatin ViiV Glbal Media enquiries: Sébastien Desprez ViiV US Media enquiries: Marc Meachem GSK Glbal Media enquiries: David Daley Melinda Stubbee GSK Analyst/Investr enquiries: Ziba Shamsi +44 (0) Kirsty Cllins (SRI & CG) +44 (0)

5 Tm Curry Gary Davies +44 (0) James Ddwell +44 (0) Jeff McLaughlin Lucy Singah +44 (0) Triumeq US label. 2 Centers fr Disease Cntrl and Preventin. HIV Basics. Accessed July 28, NHS Chices, HIV and AIDS Overview. Accessed July 28, The AIDS Treatment fr Life Internatinal Survey (ALT2010). a%20final.pdf. Accessed July 28, IAPAC Mnthly. Vlume 12, Number 5. Accessed July 28, Walmsley SL, Antela A, Clumeck N et al; fr the SINGLE Investigatrs. Dlutegravir plus Abacavir Lamivudine fr the Treatment f HIV-1 Infectin. N Engl J Med. 2013; 369(19): Walmsley S, Berenguer J, Khung-Jsses M, et al. Dlutegravir regimen statistically superir t efavirenz/tenfvir/emtricitabine: 96-week results frm the SINGLE study (ING114467). Pster presented at: 21st Cnference n Retrviruses and Opprtunistic Infectins; March 3-6, 2014; Bstn, MA. Pster Weller S, Chen S, Brland J et al. Biequivalence f a Dlutegravir, Abacavir and Lamivudine Fixed-Dse Cmbinatin Tablet and the Effect f Fd. JAIDS May di: /qai f_a_dlutegravir,_abacavir_and aspx. Atripla is a registered trademark f Bristl-Meyers Squibb and Gilead Sciences LLC.