Cork, Ireland (ots/PRNewswire)
Results from a Phase 3 head-to-head study showed that a
significantly greater percent (77 percent) of treatment-experienced
HIV-1 infected adults(i) taking Prezista(R) (darunavir)/ritonavir,
with an optimised background regimen (OBR) of antiretroviral agents,
reached a viral load of less than 400 copies/mL at week 48, compared
to 68 percent of patients taking the widely prescribed medication
lopinavir/ritonavir, with OBR, in a per-protocol analysis (95 percent
confidence interval 2-16). In addition, significantly more patients
receiving darunavir/r in this study reached an undetectable viral
load (<50 copies/mL) compared to patients taking lopinavir/r (71
percent vs. 60 percent).
The 48-week efficacy and safety results, published in the 7 July
2007 issue of The Lancet, will also be presented at the 4th
International AIDS Society Conference on HIV Pathogenesis, Treatment
and Prevention (IAS 2007) in Sydney, Australia on 24 July 2007.
The study met both the primary and secondary objective of
non-inferiority and superiority. The primary objective was to
demonstrate non-inferiority in virologic response with
darunavir/ritonavir versus lopinavir/ritonavir, both combined with an
individualised OBR, at week 48. If non-inferiority was established,
the secondary objective was to demonstrate superiority in virologic
response with darunavir/ritonavir versus lopinavir/ritonavir at week
48. Virologic response was defined as a confirmed plasma viral load
of <400 copies/mL.
"The POWER studies have shown us that darunavir is an option for
highly treatment experienced patients, and the results of TITAN
demonstrate that darunavir is also a treatment option for patients
with early virological failure, which is representative of patients
commonly encountered in clinical practice," said Jose Valdez Madruga,
M.D., Centro de Referencia e Treinamento DST/AIDS, Mariana-Sao Paulo,
Prezista, co-administered with low dose ritonavir (r), is
indicated in combination with other antiretroviral medicinal products
for the treatment of human immunodeficiency virus (HIV-1) infection
in highly pre-treated adult patients who failed more than one regimen
containing a protease inhibitor (PI). Prezista is currently approved
in several areas including the United States, Canada, and the
European Union, among others, and applications for approval also have
been submitted or are planned for submission in many other countries.
About the TITAN study
TITAN (TMC114/r In Treatment-experienced patients Naive to
lopinavir) is an ongoing, randomised, controlled, open-label Phase 3
trial in which 595 treatment-experienced patients were treated.
Participants enrolled in the study were lopinavir/r-naive, HIV-1
infected adults with a viral load of >1000 HIV-1 RNA copies/mL and
had previously failed highly active antiretroviral therapy (HAART)
after at least 12 weeks of treatment, or were currently on structured
treatment interruption. Patients with previous or current use of
lopinavir, darunavir, tipranavir, and/or enfuviritide were excluded,
as were those currently receiving treatment with investigational
antiretroviral drugs. Of the 595 patients, 31 percent were protease
inhibitor-naive and the majority were susceptible to four or more
Patients were randomised to receive darunavir/r (600 mg/100 mg)
twice daily or lopinavir/r (400 mg/100 mg) twice daily, plus OBR.
Investigator-selected OBR for each participant was chosen based on
resistance testing and prior treatment history and included a
combination of nucleoside reverse transcriptase inhibitors with or
without non-nucleoside reverse transcriptase inhibitors.
TITAN 48-week study results
Among patients randomised to the darunavir/r arm (total n=298) vs.
the lopinavir/r arm (total n=297), the 48-week per-protocol analysis
showed for the primary endpoint that 77 percent of patients in the
darunavir/r arm vs. 68 percent of patients in the lopinavir/r arm
reached a viral load of <400 copies/mL (95 percent CI 2-16).
Pre-planned secondary endpoint findings include:
-- 71 percent of patients in the darunavir/r arm reached an undetectable
viral load (<50 copies/mL) vs. 60 percent of patients in the
lopinavir/r arm, a statistically significant difference (p=0.005)
-- 77 percent of patients in the darunavir/r arm achieved at least a 1
log10 reduction in HIV RNA vs. 69 percent in the lopinavir/r arm, a
statistically significant difference (p=0.028)
-- The median increase from baseline in CD4 cell count was similar
between the darunavir/r and lopinavir/r arms (88 cells per cubic
millimeters vs. 81 cells per cubic millimeters)
Development of resistance also was studied. Findings include:
-- 10 percent of patients in the darunavir/r arm experienced virological
failure vs. 22 percent of patients in the lopinavir/r arm
-- Among patients experiencing virologic failure who had baseline and
endpoint genotype data, 21 percent of patients in the darunavir/r arm
developed primary PI resistance mutations vs. 36 percent of patients
in the lopinavir/r arm, and 14 percent of patients in the darunavir/r
arm developed primary NRTI resistance mutations vs. 27 percent of
patients in the lopinavir/r arm
The majority of adverse events in both arms were mild to moderate
in severity, with a low incidence of discontinuation. In the
darunavir/r arm, the most frequently reported adverse events (greater
or equal to 10 percent of subjects) regardless of severity were
diarrhoea (32 percent), nausea (18 percent), nasopharyngitis (12
percent), headache (11 percent), and upper respiratory tract
infection (10 percent). In the lopinavir/r arm, the most frequently
reported adverse events were diarrhoea (42 percent), nausea (21
percent) and nasopharyngitis (11 percent). Grade 2-4 diarrhoea
occurred in 8 percent of patients taking darunavir/r compared with 15
percent of patients taking lopinavir/r. Skin rash (all grades
regardless of causality) occurred in 16 percent of patients receiving
darunavir/r compared with 7 percent of patients receiving
lopinavir/r. Most rashes were mild and did not lead to
discontinuation. 0.7 percent of patients in the darunavir/r group
discontinued due to rash, compared to none in the lopinavir/r group.
Discontinuations due to adverse events were 7 percent in the
darunavir/r arm vs. 7 percent in the lopinavir/r arm.
Important Safety Information
Darunavir does not cure HIV infection or AIDS, and does not
prevent passing HIV to others.
In the registrational studies, darunavir was generally well
tolerated versus the investigator selected PIs. The majority of the
adverse reactions reported during treatment with darunavir
co-administered with 100 mg ritonavir twice daily were mild to
moderate in severity. The most frequently reported moderate to severe
adverse reactions of at least grade 2 severity were diarrhoea (2.6%),
vomiting (2.2%) and hypertriglyceridaemia (2.0%). The most commonly
reported adverse reactions of any grade were nausea (7.2%), diarrhoea
(6.6%) and headache (3.3%). Skin rash can also appear but this is
usually mild to moderate. One percent of patients discontinued
treatment due to adverse events.
People who are allergic to darunavir or any of its ingredients, or
ritonavir should not take darunavir. Before taking darunavir,
patients should tell their doctor if they have any medical
conditions, including diabetes, liver problems, haemophilia, or
allergy to sulfa medicines and should tell their doctor if they are
pregnant or planning to become pregnant, or are breastfeeding.
Darunavir should not be used in patients with severe liver problems.
There were some relevant drug-drug interactions with other
medications commonly used in HIV patient populations, such as other
antiretroviral medications and lipid lowering agents. 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.
Please see full Prescribing Information for more details.
Darunavir was developed by Tibotec Pharmaceuticals Ltd. and is
marketed in the European Union and other countries by Tibotec, a
division of Janssen-Cilag. In the U.S., darunavir is marketed by
Tibotec Therapeutics, a division of Ortho Biotech Products, L.P. In
Canada, darunavir is marketed by Tibotec, a division of Janssen-Ortho
About Tibotec Pharmaceuticals Ltd.
Tibotec Pharmaceuticals Ltd., based in Cork, Ireland, is a
pharmaceutical research and development company. The Company's main
research and development facilities are in Mechelen, Belgium with
offices in Yardley, PA. Tibotec is dedicated to the discovery and
development of innovative HIV/AIDS drugs and anti-infectives for
diseases of high unmet medical need.
Tibotec Pharmaceuticals is developing a Global Access Program to
facilitate access to its antiretrovirals for patients living with
HIV/AIDS in developing countries. The Global Access Program for
darunavir includes access pricing, registration, medical education
for appropriate use and voluntary licensing.
Tibotec, a division of Janssen-Cilag, will bring innovative
products for HIV/AIDS to patients in Europe, the Middle East and
Africa This new division was created within the Janssen-Cilag
companies in October 2005 to focus on patients' and health care
providers' specific needs in this disease domain. The company will
also commercialise medicine to combat other viral diseases in the
Janssen-Cilag is a leader in traditional and biological medicines
for disorders such as in gastroenterology, women's health, mental
health and neurology as well as for pain, oncology, haematology and
Contact: Hans Vanavermaete
(i) The TITAN Study included mild, moderate and highly
treatment-experienced patients, which is outside the current licensed
indication for PREZISTA in highly treatment-experienced patients.
ots Originaltext: Tibotec
Im Internet recherchierbar: http://www.presseportal.ch
Hans Vanavermaete, Mobile, +32-(0)-478-447-278, or Office,
+32-(0)-15-461-017, for Tibotec