New Data Show Oral Valcyte(R) (valganciclovir) as Effective as iv Ganciclovir for Treatment of CMV Disease in Transplant Patients

Basel, Switzerland (ots/PRNewswire) - Results of the landmark
VICTOR study presented today at the American Transplant Congress,
San Francisco, USA, have shown that Valcyte (oral valganciclovir) is
as effective and as well tolerated as intravenous ganciclovir, the
current gold-standard for the treatment of cytomegalovirus (CMV)
infection in solid organ transplant patients(1),(2). This is good
news for both physicians and patients as it means that effective
anti-CMV medication can now be administered orally: a more
convenient and economic option when compared to the intravenous
alternative.

Professor Anders Hartmann, Professor of Nephrology, University of
Oslo, Norway, and the study's principal investigator said: "The
results of the VICTOR study will enable clinicians to modernise their
CMV management practices with confidence. These important data show
that oral valganciclovir has clinical equivalence to the current
gold-standard treatment, intravenous ganciclovir, but with the added
obvious patient benefits that are present in every oral formulation.

"Compared to intravenous ganciclovir, oral valganciclovir
treatment is more convenient for patients, as it can be
self-administered at home. This means that many hospitalised
transplant patients with CMV disease can be discharged sooner,
resulting in reduced physician workloads, and much-needed episodal
cost-savings."

CMV is the single most common viral infection in organ transplant
Recipients(3), and is also very common among the general population.
It is estimated that 50-80% of all adults have been infected with the
virus(4).

CMV infection usually develops during the first few months after
transplantation and may cause complications in the lungs, kidneys,
nervous system, stomach, liver, brain, and eyes(3),(5).

The randomised, interventional study involved 321 solid organ
transplant recipients with virologic and clinical evidence of CMV
disease after transplantation. One-hundred-and-sixty-four patients
received a 21-day course of oral valganciclovir (VGCV; 900 mg/day
b.d.), and one-hundred-and-fifty-seven patients received intravenous
ganciclovir (GCV; 5 mg/kg/day b.d.). Following that, all patients
received a 28-day maintenance course of valganciclovir (900 mg/day
q.d.).

Clinical resolution of CMV disease was similar at all time points.
At Day 21, clinical success (as assessed by the investigator) was
achieved in 83.6% of patients in the VGCV treatment group and 84.0%
in the GCV arm. At Day 49, success rates were 96.6% for VGCV versus
93.0% for GCV. Viral clearance did not differ between treatment
groups at Day 21 (VGCV: 45.1% vs GCV: 48.4%) or at Day 49 (82.7% vs
87.3%).

Both treatments were well tolerated, compliance rates were
similar, and there was no difference in the adverse event profile,
including leukopenia. The investigators concluded that these findings
would have major implications for the management of CMV disease, for
patients, physicians, and health-care providers(1),(2).

About valganciclovir (Valcyte(R))

Valcyte, the oral pro-drug of ganciclovir, is indicated for the
prevention of CMV disease in kidney, kidney-pancreas, and heart
transplant patients at high risk. Valcyte is not approved for use in
liver transplantation. The efficacy and safety of Valcyte in other
solid organ transplants, such as lung transplant, have not been
established.

The clinical toxicity of Valcyte, which is metabolised to
ganciclovir, includes granulocytopenia, anaemia and thrombocytopenia.
In animal studies, ganciclovir was carcinogenic, teratogenic and
caused aspermatogenesis. Valcyte tablets should not be administered
if the absolute neutrophil count is less than 500 cells/microlitre,
the platelet count is less than 25,000/microlitre, or the haemoglobin
count is less than 8 g/dL. Severe leukopenia, neutropenia, anaemia,
thrombocytopenia, pancytopenia, bone marrow depression, and aplastic
anaemia have been observed in patients treated with Valcyte tablets
(and ganciclovir). Other adverse events reported with a frequency of
greater than or equal to 5% included diarrhoea, tremors, fever,
nausea, headache, vomiting, insomnia, and allograft rejection.

About Roche

Headquartered in Basel, Switzerland, Roche is one of the world's
leading research-focused healthcare groups in the fields of
pharmaceuticals and diagnostics. As the world's biggest biotech
company and an innovator of products and services for the early
detection, prevention, diagnosis and treatment of diseases, the Group
contributes on a broad range of fronts to improving people's health
and quality of life. Roche is the world leader in in-vitro
diagnostics and drugs for cancer and transplantation, a market leader
in virology and active in other major therapeutic areas such as
autoimmune diseases, inflammation, metabolism and central nervous
system. In 2006 sales by the Pharmaceuticals Division totalled 33.3
billion Swiss francs, and the Diagnostics Division posted sales of
8.7 billion Swiss francs. Roche employs roughly 75,000 worldwide and
has R&D agreements and strategic alliances with numerous partners,
including majority ownership interests in Genentech and Chugai.
Additional information about the Roche Group is available on the
Internet at www.roche.com.

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Additional information:

About the VICTOR study

The VICTOR study was a comparative, randomised, phase IV,
intervention study involving 321 solid organ transplant recipients
with virologic and clinical evidence of CMV disease after
transplantation.

The primary study objective was to compare the efficacy and safety
of oral valganciclovir (VGCV; 900 mg/day b.d.; n=164) with
intravenous ganciclovir (GCV; 5 mg/kg/day b.d.; n=157). The study's
primary endpoint was non-inferiority in the eradication of CMV
viremia at day 21.

The study population consisted of kidney (n=73.8%), heart
(n=5.6%), liver (n=7.2%) and other/combined (n=13.4%) transplant
recipients. There was clinical diagnosis of tissue invasive disease
in 46% of patients. Patients received their allocated study drug for
21 days. All patients then received valganciclovir maintenance
therapy (900 mg/day q.d.) for a further 28 days. CMV viral loads were
determined centrally at Days 0, 3, 7, 10, 14, 17, 21, 28, 35, 42 and
49.

During the first 21 days, the study drug was discontinued in 11
(6.7%) of the patients in the VGCV group versus 7 (4.5%) in the GCV
group (p=NS). Viral clearance did not differ between treatment groups
at Day 21 (VGCV: 45.1% versus GCV: 48.4%) and at Day 49 (82.7% versus
87.3%). Median viral load half-life was 11.5 days in the VGCV arm and
10.4 days in the GCV arm (p=NS). Median Kaplan Meier estimates of
time to viral eradication were similar in both treatment arms (21
days for VGCV versus 19 days for GCV). Clinical resolution of CMV
disease was similar at all time points. At Day 21, clinical success,
as assessed by the investigators, was achieved in 83.6% of patients
in the VGCV treatment group and 84.0% in the GCV arm; at Day 49,
these rates were 96.6% and 93.0% respectively. The most important
factor influencing time to eradication was the initial viral load.

Both treatments were well tolerated, compliance was similar, and
there was no difference in the adverse event profile, including
leukopenia. The investigators concluded that for SOT recipients with
CMV disease, oral VGCV has comparable safety and efficacy to IV GCV,
and that each treatment provides equivalent viral clearance kinetics.

They added that these findings would have major implications for
the management of CMV disease, for patients, physicians and
health-care providers.

Full results of the VICTOR study will be published at a later
date.

About cytomegalovirus (CMV) infection and disease

CMV, otherwise known as cytomegalovirus, is a virus that infects
people of all ages. It is similar in structure to the viruses that
cause herpes and chickenpox(6).

CMV infection is very common among the general population. It is
estimated that 50-80% of all adults have been infected with the
virus(4). CMV is also the single most common viral infection in organ
transplant recipients(3).

CMV is usually spread through transmission of body fluids,
including urine, saliva, breast milk, blood, tears, semen, and
vaginal fluids. Typically, a person becomes infected with CMV when
they come in frequent, regular contact with these infected body
fluids(6). The most common way for transplant recipients to contract
CMV infection is when their donor has been infected with the virus.

Most cases of CMV infection remain undiagnosed, because the
infected person usually has few or no symptoms. However, symptomatic
CMV disease develops when a person's immune system cannot control
their CMV infection. In the vast majority of cases, the immune system
renders the virus harmless. However, CMV can be particularly serious
in people who have received organ transplants and whose immune
systems are weakened (i.e. through the use of immunosuppressive
medications)(5).

CMV infection usually develops during the first few months after
transplantation and may cause complications in the lungs, nervous
system, stomach, liver, brain, and eyes(3),(5).

CMV is strongly associated with the following diseases:(3),(4)

- hepatitis

- pancreatitis

- stomach ulcers

- gastrointestinal infection

- pneumonia.

It can also increase the risk of organ rejection(3).

Organ recipients who are already infected, or who receive an
infected organ, can prevent the progression to CMV disease by using
antiviral drugs such as ganciclovir and valganciclovir(6). Normally,
this anti-CMV medication is given during the first few months after
transplantation, as this is when the risk of contracting CMV disease
is greatest. However, anti-CMV medication may be prescribed later
than six months post-transplantation if doses of immunosuppressive
medications are increased following a rejection episode.

References:

1. Hartmann A. Oral valganciclovir is as effective and safe as IV
ganciclovir for the treatment of cytomegalovirus disease in solid
organ transplant recipients. Data presented at the American
Transplant Congress, San Francisco, US, 5-9 May 2007. Abstract number
950336.

2. Humar A. Oral valganciclovir and intravenous ganciclovir have
comparable cytomegalovirus (CMV) viral clearance kinetics in the
treatment of CMV disease. Data presented at the American Transplant
Congress, San Francisco, US, 5-9 May 2007. Abstract number 950110.

3. Medscape. Infection in the Transplant Recipient: CMV. Accessed
on 30 April 2006. at: http://www.medscape.com/viewarticle/451788_7

4. PatientPlus. Cytomegalovirus (CMV). Accessed on 30 April 2006
at: http://www.patient.co.uk/showdoc/40000377/

5. KidsHealth. Infections: Cytomegalovirus. Accessed on 30 April
2006 at: http://kidshealth.org/parent/infections/bacterial_viral/cyto
megalovirus.html

6. Centers for Disease Control and Prevention. Frequently Asked
Questions About CMV. Accessed on 30 April 2006 at:
http://www.cdc.gov/cmv/faqs.htm

ots Originaltext: Roche Pharmaceuticals
Im Internet recherchierbar: http://www.presseportal.de

Contact:
Media relations contacts: Julia Pipe, International Communications
Manager, Roche Transplant, Mobile tel: +41-79-263-9715, Office tel:
+41-61-687-4376, E-mail: julia.pipe@roche.com; Steve Dawber,
Freelance Medical Journalist, Mobile tel: +44-7966-197-701, Office
tel: +44-1925-211-909, E-mail: steve.dawber@btinternet.com