COLOGNE, Germany - 12 November 2009 - 48 week data presented today by Tibotec, a division of Janssen-Cilag, demonstrates that a once daily dose of PREZISTA (darunavir), a protease inhibitor, boosted with ritonavir (r) as a monotherapy is non-inferior to the same boosted dose of darunavir taken in combination with other antiretrovirals in treatment-experienced HIV-positive adults. Patients included in the study had baseline viral loads of less than 50 copies/mL, were virologically suppressed and had no history of virologic failure while on combination therapy. The data comes from a phase IIIb, multi-centre, open-label trial called MONET (Monotherapy in Treatment-Experienced Adults).

In addition to the MONET 48-week efficacy results, Tibotec is presenting 21 other abstracts on its compounds at the European AIDS Society Conference in Cologne, Germany. These abstracts include 96-week efficacy and safety data on once daily darunavir in treatment-naive patients (ARTEMIS study). Tibotec is also presenting 96-week safety and efficacy data on its non-nucleoside reverse transcriptase inhibitor etravirine (DUET studies) as well as data on TMC278, its third antiretroviral which is in late stage clinical development (ECHO and THRIVE studies).

"Darunavir has been available as a twice daily formulation for treatment-experienced adult patients for the past year and in that short time has already made a significant contribution to treatment options," said Dr. Jose Arribas, lead MONET investigator, Hospital de La Paz, Madrid, Spain. "The studies on darunavir demonstrate the efficacy of darunavir, both as a monotherapy or in combination with other antiretrovirals for adults living with HIV."



For treatment-experienced adult patients, the current licensed dosing for darunavir is 600 mg taken with 100 mg ritonavir twice daily with food in combination with other antiretrovirals.

About the MONET study

The MONET study compares the efficacy of once daily darunavir/r 800 mg/100 mg monotherapy with once daily darunavir/r 800 mg/100 mg used in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) in 256 treatment-experienced HIV-1 adults who were virologically suppressed and had no history of virologic failure while on combination therapy. The primary objective was to demonstrate non-inferiority (with a margin of 12%) of once daily darunavir monotherapy with the same dose taken in combination with two NRTIs for confirmed virologic response defined as plasma HIV-1 RNA < 50 copies/mL. The primary objective was reached at week 48 when 86.2 percent of patients in the once daily monotherapy arm reached an undetectable viral load (<50 copies/mL), compared with 87.8 percent of patients taking darunavir/r once daily in combination with two NRTIs arm. The estimated difference in virologic response between the treatment arms was 1.6 percent (lower limit of 95% CI of -10.1 percent, confirming non-inferiority).

Patients were randomised between the two treatment arms. Patients in the darunavir/r plus two NRTIs arm could change NRTIs both at baseline and during the trial as needed. Patients had been on HAART for over 24 weeks (either NRTI based (43 percent) or PI based (57 percent)). Patient randomization was stratified based on pre-treatment at time of screening. One patient per arm had evidence of genotypic resistance to darunavir. No patients had evidence of phenotypic resistance to darunavir.



Darunavir was developed by Tibotec Pharmaceuticals and is marketed in Europe by Tibotec, a division of Janssen-Cilag.

Licensed dosing for European countries

For treatment-experienced adult patients, the licensed dosing for darunavir is 600 mg taken with 100 mg ritonavir twice daily with food. For treatment-naive adult patients, the licensed dosing for darunavir is 800 mg taken with 100 mg ritonavir once daily with food. Darunavir must be taken in combination with other antiretroviral agents. Darunavir/r is not recommended for use in patients with severe hepatic impairment.

Important Safety Information

In the registrational studies, darunavir was generally well tolerated. The majority of the adverse reactions reported in patients who initiated therapy with darunavir 600 mg co-administered with 100 mg ritonavir twice daily were mild to moderate in severity. Thirty percent of the patients experienced at least one adverse drug reaction (at least grade 2 in severity and considered by the investigator at least possibly related to darunavir co-administered with 100 mg ritonavir). The most frequently (greater than or equal to 2 percent) of those reported adverse reactions were diarrhoea (3.9 percent), hypertriglyceridaemia (3.8 percent), rash (2.8 percent), nausea (2.6 percent), hypercholesterolaemia (2.5 percent) and headache (2.0 percent). 2.6 percent of the patients discontinued treatment due to adverse reactions.



Before taking darunavir, patients should tell their doctor if they have any medical conditions, including liver problems, including hepatitis B or C, diabetes, symptoms of infections, change in body fat, haemophilia, musculoskeletal problems, or allergy to sulfa medicines and should tell their doctor if they are pregnant or planning to become pregnant, or are nursing. Darunavir should not be used in patients allergic (hypersensitive) to darunavir or ritonavir or with severe liver problems.



Due to potential drug interactions, patients should talk to their healthcare provider about all the medicines they are taking or plan to take, including prescription and non-prescription medicines, vitamins, and herbal supplements.



Darunavir does not cure HIV infection or AIDS, and does not prevent passing HIV to others.

Please see full Summary of Product Characteristics for more details.

About Tibotec Pharmaceuticals

Tibotec Pharmaceuticals, based in Cork, Ireland, is a pharmaceutical research and development company, with offices in Yardley, PA, USA and its main research and development operations in Mechelen, Belgium. Tibotec is dedicated to the discovery and development of innovative HIV/AIDS drugs and anti-infectives for diseases of high unmet medical need.

About Tibotec, a division of Janssen-Cilag

Tibotec, a division of Janssen-Cilag, brings innovative products for HIV/AIDS to patients in Europe, the Middle East and Africa focusing on patients' and healthcare providers' specific needs in this disease domain. The company is working to make available medicines to combat other viral diseases in the future.

About Janssen-Cilag

Janssen-Cilag is a leader in traditional and biological medicines for disorders such as gastroenterology, women's health, mental health and neurology as well as for pain, oncology, haematology and nephrology.



Tibotec Pharmaceuticals and Janssen-Cilag are subsidiaries of the Johnson & Johnson family of companies.

NOTES TO THE EDITOR

Tibotec Data at EACS



Darunavir

• Non-inferior efficacy shown across different efficacy endpoints in the MONET trial of darunavir/ritonavir (DRV/r) monotherapy
• Cost-efficacy analysis of the MONET trial using German antiretroviral drug prices
• Analysis of drug resistance during HIV RNA viraemia in the MONET trial of darunavir/ritonavir (DRV/r) monotherapy
• Low-level HIV RNA viraemia in the MONET trial: effects of assay variability and inter-current infection
• ARTEMIS 96-week comparison of liver tolerability of once-daily darunavir/ritonavir (DRV/r) versus lopinavir/ritonavir (LPV/r) in treatment-naïve patients
• Comparison of Gastrointestinal Adverse Events (GI AEs) of Darunavir/Ritonavir (DRV/r) and Lopinavir/Ritonavir (LPV/r) at Week 96 in ARTEMIS
• A phase II, open-label trial in treatment-naïve, HIV-1 infected subjects who received DRV/RTV as induction monotherapy
• Rates and predictors of adherence in treatment-experienced women and men in GRACE (Gender, Race And Clinical Experience)
• PK/PD analyses of darunavir in treatment-experienced women and men in GRACE (Gender, Race And Clinical Experience)
• Comparative regimen durability and discontinuation reasons among 3-class experienced patients in a US clinical cohort
• Use of twice daily darunavir as a substitution for dual boosted PIs in virologically suppressed patients: primary endpoint results of a pilot randomized clinical trial

Etravirine

• Etravirine demonstrates a favourable safety and tolerability profile vs placebo irrespective of hepatitis co-infection: week 96 analysis from the DUET trials
• Etravirine (ETR) demonstrates a favourable safety and tolerability profile: pooled 96-week results from the phase III duet trials
• Safety and pharmacokinetics (PK) of etravirine (ETR) in pregnant HIV-infected women
• Pharmacokinetic interaction between etravirine and lopinavir/ritonavir in HIV-negative volunteers
• The economic impact of national particularities in the health care system. Calculation for hospital-related costs from pooled DUET trials by German-DRGs
• Cost-effectiveness of current treatment options in treatment resistant HIV/AIDS patients in the German setting

TMC278

• TMC278 25mg QD has no effect on corrected QT interval in a study in HIV-negative volunteers
• Absorption, metabolism and excretion of TMC278, a next-generation NNRTI, after a single oral dose of 150mg in healthy male volunteers
• Absence of a teratogenic potential from a novel next-generation NNRTI, TMC278
• PK interaction study between TMC278, a next-generation NNRTI, and the contraceptives norethindrone plus ethinylestradiol

Protease Inhibitors

Darunavir is part of a group of anti-HIV treatments called protease inhibitors, which stop the replication of the HIV virus by attacking an enzyme in HIV, called protease. Nearly all the protease inhibitors used today are "boosted." This means they have their power increased by the addition of a small dose of a second protease inhibitor called ritonavir.¹



Viral Load

The amount of HIV in a patient's blood is called viral load. Reduction of viral load is the goal of all HIV treatment. A high viral load means that a patient is at increased risk of losing CD4+ cells, which help the body fight infection. Low viral loads (<50 copies/ml) are said to be undetectable; however, this does not necessarily mean that the virus has been eradicated or that the patient is no longer infectious.²



CD4+ Cell Count

CD4+ cells are white blood cells that help the body fight disease. CD4+ cell counts are used to monitor the effectiveness of HIV treatment and to help determine when to begin anti-HIV therapy. A healthy, HIV-negative adult will have a CD4+ cell count between 600 and 1200 CD4+ cells/mm of blood;3 however, for many adults living with HIV, this count is much lower. A low CD4+ cell count indicates that the immune system is weakened and the body is at increased risk of infections.³



References

1. NAM. HIV treatment [Online] 2009 Jan 5 [cited 2009 Jan 12]; Available from: www.aidsmap.com/cms1044497.asp.

2. NAM. Viral load [Online] 2009 Jan [cited 2009 Jan 12]; Available from: www.aidsmap.com/cms1044622.aspx.

3. NAM. CD4 cell counts [Online] 2009 Jan [cited 2009 Jan 12]; Available from: www.aidsmap.com/cms1044596.aspx.

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