One hundred twelve patients with acromegaly previously treated with surgery, radiation
therapy, and/or medical therapies participated in a 12-week, randomized, double-blind,
multi-center study comparing placebo and SOMAVERT. Following withdrawal from previous
medical therapy, the 80 patients randomized to treatment with SOMAVERT received
a subcutaneous (SC) loading dose, followed by 10, 15, or 20 mg/day SC. The three
groups that received SOMAVERT showed dose-dependent reductions in serum levels of
IGF-I, free IGF-I, IGFBP-3, and ALS compared with placebo at all post-baseline visits
(Figure 1 and Table 1).
Figure 1. Effects of SOMAVERT on Serum Markers (Mean ± Standard Error)
After 12 weeks of treatment, serum IGF-I levels were normalized in 10%, 39%, 75%,
and 82% of subjects treated with placebo, 10, 15, or 20 mg/day of SOMAVERT, respectively
(Figure 2).
Figure 2. Percent of Patients Whose IGF-I Levels Normalized at Week 12
Table 2 shows the effect of treatment with SOMAVERT on ring size (standard jeweler's
sizes converted to a numeric score ranging from 1 to 63), and on both the total
and individual scores for signs and symptoms of acromegaly. Each individual score
(for soft-tissue swelling, arthralgia, headache, perspiration and fatigue) was based
on a nine-point ordinal rating scale (0 = absent and 8 = severe and incapacitating),
and the total score was derived from the sum of the individual scores. Mean baseline
scores were as follows: ring size = 47.1; total signs and symptoms = 15.2; soft
tissue swelling = 2.5; arthralgia = 3.2; headache = 2.4; perspiration = 3.3; and
fatigue = 3.7.
Table 1. Mean Percent Change from Baseline in IGF-I at Week 12 for Intent-to-Treat
Population
Table 2. Mean Change from Baseline (SD) at Week 12 for Ring Size and Signs and Symptoms
of Acromegaly
Ring size at week 12 was smaller (improved) in the groups treated with 15 or 20
mg of SOMAVERT, compared with placebo. The mean total score for signs and symptoms
at week 12 was lower (improved) in each of the groups treated with SOMAVERT, compared
with the group treated with placebo.
Serum growth hormone (GH) concentrations, as measured by research assays using antibodies
that do not cross-react with pegvisomant (see PRECAUTIONS, Drug/Laboratory Test Interactions),
rise within two weeks of beginning treatment with SOMAVERT. The largest GH response
was seen in patients treated with doses of SOMAVERT greater than 20 mg/day. This
effect is presumably the result of diminished inhibition of GH secretion as IGF-I
levels fall. As shown in Figure 3, when patients with acromegaly were given a loading
dose of SOMAVERT followed by a fixed daily dose, this rise in GH was inversely proportional
to the fall in IGF-I and generally stabilized by week 2. Serum GH concentrations
also remained stable in patients treated with SOMAVERT for up to 18 months.
Figure 3. Percent Change in Serum GH and IGF-I Concentrations
Another cohort of 38 patients with acromegaly was treated with SOMAVERT in a long-term,
open-label, dose-titration study and received at least 12 consecutive months of
daily dosing with SOMAVERT (mean = 55 weeks). The mean (± standard deviation) IGF-I
concentration at baseline in this cohort was 917 (± 356) ng/mL after withdrawal
from previous medical therapy, falling to 268 (± 134) ng/mL at the end of treatment
with SOMAVERT. Thirty-five of the 38 patients (92%) achieved a normal (age-adjusted)
IGF-I concentration. After the first visit at which a normal IGF-I concentration
was observed, IGF-I levels remained within the normal range at 92% of all subsequent
visits over a mean duration of one year.