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Studies
Confirm Effectiveness of Serostim (Growth Hormone) for AIDS Wasting
and Demonstrate Potential Benefits for Lipodystrophy
Serono
SA announced positive results of two major clinical trials of Serostim
[somatropin (rDNA origin) for injection] for the treatment of AIDS-related
metabolic complications at the XIV International AIDS Conference
in Barcelona, Spain. Results of both trials will be presented as
late breaker sessions at the Barcelona meeting.
AIDS Wasting
AIDS
wasting is a chronically debilitating
and potentially life-threatening condition. It is a metabolic
disorder that causes the body to use vital muscle and organ tissue,
which is critical for survival, for energy instead of primarily
using the body’s stored fat.
People with AIDS wasting usually experience a loss
of 5-10% or more of lean body mass.
The result can lead to increased risk for opportunistic infections
and illness, and extreme fatigue and can profoundly diminish a person’s
quality of life.
HIV-Related
Lipodystrophy
HIV-associated
lipodystrophy is characterized by a variety of metabolic disturbances
and body shape abnormalities that may present individually or in
combination. These abnormalities include elevated cholesterol levels,
insulin resistance, abnormal fat depletion and/or abnormal fat accumulation.
Patients with HARS, a subset of HIV-associated lipodystrophy, experience
abnormal, pathological accumulation of adipose tissue, which may
be present with or without fat depletion and/or metabolic abnormalities.
Serostim
for the Treatment of Adipose Redistribution Syndrome (STARS)
Study
The Serostim
for the Treatment of Adipose Redistribution Syndrome study
(STARS), a Phase II/III, double-blind, placebo-controlled study,
designed to evaluate Serostim as a potential therapy
for HIV-Associated Adipose Redistribution Syndrome (HARS), demonstrated
positive results in reducing adipose tissue maldistribution. HARS,
a subset of a condition called HIV-related lipodystrophy syndrome,
consists of abnormal fat distribution and altered metabolism.
Serono is working
with the US Food and Drug Administration (FDA) to finalize plans
for the continued development of this program. Serostim is currently
not approved for the treatment of HARS.
“The results
of the STARS study indicate that Serostim has a potential
role in the treatment of body composition issues associated with
lipodystrophy, which is an important finding for a condition that
has a significant impact on HIV positive patients in the US who
experience some form of fat maldistribution or lipodystrophy,” said
lead investigator, Donald Kotler, MD, St. Luke’s Roosevelt Hospital,
New York. “The STARS trial is a critical step to learning more
about the condition and potential therapies.”
The STARS trial
involved 239 patients at trial sites located throughout the US.
The primary objective of the STARS study was to determine whether
Serostim treatment reduces adipose tissue maldistribution
more effectively than placebo. The co-primary endpoints were a
reduction in visceral adipose tissue (VAT) as assessed by CT [1] scan and the ratio
of trunk to limb fat as assessed by DXA
[2] technology. Secondary endpoints included Serostim’s
effect on lean body mass and quality of life/body image self
assessment. Patients were randomized into three treatment groups,
which included Serostim 4 mg daily, SerostimŇ
4 mg on alternate days and placebo.
The first co-primary
endpoint shows that the decrease in VAT from baseline to week 12
was highly significant in the Serostim 4 mg daily group
(p<0.001) as compared to placebo. The mean reduction in the
area of VAT across the mid-abdomen in males receiving Serostim
4mg daily was 31.0cm2 (9.2% of the baseline mean
value) and 34.2cm2 (13.5% of the baseline mean value)
for females. The Serostim 4 mg on alternate days group
did not reach statistical significance as compared to placebo for
this endpoint. The second co-primary endpoint demonstrates that
the trunk to limb fat ratio was significantly reduced in both the
Serostim 4 mg daily (p<0.001) and Serostim 4 mg on
alternate day (p<0.001) groups compared to the placebo group.
The results
of the secondary endpoints were also positive. Compared to the placebo
group, results indicate a significant change in lean body mass from
baseline to week 12 for those receiving Serostim 4 mg
daily (p<0.001) and 4 mg on alternate days (p<0.001) groups,
with the mean increase ranging from 3.0 kg in women and 3.5 kg in
men, and 2.1 kg in women and 2.8 kg in men, respectively.
Serum total
cholesterol declined by 12.5 mg/dl in the Serostim 4 mg daily group
and by 7.5 mg/dl in the Serostim 4 mg on alternate days
group. Both of these declines were significantly greater than the
change seen in the placebo group. In addition, the change from
baseline Quality of Life summary score was more favorable on Serostim
4 mg daily (p<0.01) and on Serostim 4 mg on
alternate days (p<0.05) as compared to placebo. Adverse reactions
reported during this clinical trial were consistent with those expected
within the current approved indication for Serostim.
Serostim
AIDS Wasting Confirmatory Trial
The Serostim
AIDS wasting study, a Phase IV, confirmatory, randomized, double-blind,
dose-ranging study, confirmed the clinical efficacy of Serostim
in the treatment of AIDS wasting by achieving its primary and secondary
endpoints. Following discussions with the FDA, data from this trial
will be submitted to the agency.
“This study
confirmed that Serostim, in a dose dependent manner, was able to
restore lean body mass to patients with AIDS wasting,” said trial
investigator, Graeme Moyle, MD, Chelsea and Westminster Hospital,
London, UK. “This restoration was accompanied by direct clinical
benefits, such as improved physical performance and Quality of Life.”
The Serostim
AIDS wasting confirmatory trial included more than 700 patients
at US, EU and other international trial sites. Following the accelerated
approval of Serostim by the FDA, Serono conducted a Phase IV study
to confirm the safety and efficacy of Serostim. Trial enrollees
were randomized into three treatment groups to receive Serostim
6 mg daily, Serostim 6 mg on alternate days or placebo for a 12-week
treatment period.
The primary
endpoint of the study was to confirm the clinical efficacy of Serostim
compared with placebo, based on exercise function change as assessed
by cycle ergometer work output from baseline to week 12. The results
of the primary endpoint were positive and demonstrated a highly
significant increase of work output of 9.9% in the group treated
with Serostim 6 mg daily and a decrease of 1% in the placebo group.
The secondary
endpoint was the change in lean body mass as measured by bioimpedance
spectroscopy (BIS) from baseline to week 12. Findings demonstrate
a dose-response relationship. The quantity of lean tissue gained
in the group treated with Serostim 6mg daily (median gain in lean
body mass 5.2 kg) and in the group treated with Serostim 6 mg on
alternate days (median gain in lean body mass 3.3 kg) was significantly
greater compared to the placebo group (median gain in lean body
mass 0.6 kg) (p<0.0001 for both Serostim doses).
Furthermore,
patients receiving Serostim 6 mg daily had a significantly greater
effect in terms of median gain in lean body mass than those patients
receiving Serostim 6 mg on alternate days. Adverse reactions reported
during this clinical trial were consistent with those expected within
the current approved indication for Serostim.
The study used
two Quality of Life scales to assess patients’ response to treatment
with Serostim for AIDS wasting. Results were generally favorable.
When asked the question ‘Do you think this treatment has been of
benefit to you?,’ Serostim treated patients responded significantly
more favorably than those treated with placebo. In addition, patients
receiving Serostim 6 mg daily responded significantly more favorably
than those treated with Serostim 6 mg every other day.
“The positive
findings from the Serostim trials provide excellent news for the
HIV community and for people living with AIDS,” said Stevo Knezevic,
Senior Executive Vice President, Clinical Development at Serono.
“The findings of these two trials enhance our understanding of HIV-related
metabolic complications and will help us develop improved therapies.”
Serostim
Serostim is
the only growth hormone approved by the U.S. Food and Drug Administration
(FDA) for the treatment of AIDS wasting or cachexia. Serostim received
FDA accelerated approval in 1996 based upon the analysis of changes
in body weight and lean body mass in surrogate endpoints in clinical
studies up to 12 weeks in duration. Serostim is now on the market
in 12 countries.
Serostim,
when taken as prescribed in 6mg doses over 12 weeks, is generally
well tolerated. The most common adverse reactions to Serostim are
increased tissue turgor (generally swelling of hands and feet) and
musculoskeletal discomfort (pain, swelling or stiffness). Generally
mild to moderate in severity, these symptoms usually resolve spontaneously
with continued treatment or are effectively managed with analgesic
therapy or after reducing the weekly dose. Serostim must be used
in conjunction with antiretroviral therapy. Elevations in mean
blood glucose levels can also occur. Patients with other risk factors
for glucose intolerance should be monitored closely. Full prescribing information for Serostim is available at
www.aidswasting.com
07/10/02
Sources
Serono Satellite Symposium. “Long-Term Challenges of
HAART: the Patient’s Concerns.” July 6, 2002. Barcelona, Spain.
Serono
announces significant results from two clinical trials of Serostim
at the XIV International AIDS Conference. Press Release.
July 10, 2002.
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