Laboratory Changes
Elevations of serum concentrations of ALT and AST greater than ten times the ULN
were reported in two subjects (0.8%) exposed to SOMAVERT in pre-approval clinical
studies (see PRECAUTIONS, Liver Tests [LTs]).
General
Nine acromegalic patients (9.6%) withdrew from pre-marketing clinical studies because
of adverse events, including two patients with marked transaminase elevations (see
PRECAUTIONS, Liver Tests [LTs]), one patient with lipohypertrophy at the
injection sites, and one patient with substantial weight gain. The majority of reported
adverse events were of mild to moderate intensity and limited duration. Most adverse
events did not appear to be dose dependent. Table 5 shows the incidence of treatment-emergent
adverse events that were reported in at least two patients treated with SOMAVERT
and at frequencies greater than placebo during the 12-week, placebo-controlled study.
Table 5. Number of Patients (%) with Acromegaly Reporting Adverse Events in a 12-week
Placebo-controlled Study with SOMAVERT*
Immunogenicity
In pre-marketing clinical studies, approximately 17% of the patients developed low
titer, non-neutralizing anti-GH antibodies. Although the presence of these antibodies
did not appear to impact the efficacy of SOMAVERT, the long-term clinical significance
of these antibodies is not known. No assay for anti-pegvisomant antibodies is commercially
available for patients receiving SOMAVERT.
Post-Marketing Experience
Lipohypertrophy has been reported in <5% of patients following pegvisomant administration.
Asymptomatic, transient elevations in transaminases up to 15 times ULN have been
observed in <2% of patients in the post-marketing experience. These reports were
not associated with an increase in bilirubin, and there were no clinical consequences
for these patients. Transaminase elevations normalized with time, most often after
suspending treatment (SOMAVERT should be used in accordance with the information
presented in Table 4 with respect to liver test abnormalities).