Pharmaceuticals, Inc. (Nasdaq: ALXN) today announced positive data
from the 26-week extension of the AEGIS study, an open-label
registration study examining Soliris®
(eculizumab) for the treatment of Japanese patients with paroxysmal
nocturnal hemoglobinuria (PNH). The study showed that after 38 weeks
of Soliris treatment, all patients with chronic kidney disease (CKD), a
clinical consequence of chronic hemolysis, either stabilized or
improved. Other studies have shown that kidney disease accounts for 18
percent of deaths among Japanese patients with PNH. In the studied
patients, Soliris therapy was also associated with a sustained reduction
in hemolysis, which resulted in a further improvement in levels of
fatigue, as well as a maintained improvement in anemia and a reduction
in transfusion requirements.
The data were presented today at the 51st
Annual Meeting of the American Society of Hematology (ASH) in a
poster titled “Chronic
Renal Insufficiency in Japanese Patients with Paroxysmal Nocturnal
Hemoglobinuria (PNH): Improvement with Eculizumab Treatment in the
Long-Term Follow-up of the AEGIS Study.”
"Chronic kidney disease is one of the most common and life-threatening
complications of hemolysis among Japanese patients with PNH. In this
extension study, clinical improvements in kidney function with
eculizumab therapy were particularly evident in patients with early
stage kidney disease, which underscores the importance of early
intervention with eculizumab," said Yuzuru Kanakura, M.D., Ph.D.,
Professor of Hematology and Oncology at Osaka University Hospital in
Suita, Japan, and lead author of the study. “We are pleased that
eculizumab continues to show a sustained reduction in hemolysis,
beneficial effects on kidney function, and a significant improvement in
quality of life.”
Initial efficacy and safety data from the 12-week AEGIS study were
presented at the ASH meeting in 2008. This 26-week extension study,
which is still ongoing, further evaluated Soliris in Japanese patients
with PNH and allowed for a comparison with the results from the Phase
III, multinational trials conducted in the United States and Europe.
“The long-term data from the AEGIS study continue to be consistent with
those observed in the SHEPHERD and TRIUMPH Phase III clinical trials,
which also showed significant reductions in hemolysis, anemia,
transfusion dependence, and fatigue among patients with PNH in the U.S.
and Europe who were treated with Soliris,” said Leonard Bell, M.D.,
Chief Executive Officer of Alexion. “We anticipate that regulatory
authorities in Japan may make a decision on our application for
marketing authorization next year, and we are preparing to make Soliris
available to physicians and patients in Japan in late 2010.”
Clinical Data from the AEGIS Extension Study
Twenty-seven Japanese patients entered the extension of the AEGIS study.
Patients received 600 mg of Soliris every 7 days (+/- 2
days) for 4 weeks; 900 mg one week later; then 900 mg every 14 days (+/-
2 days) for a total of 38 weeks of therapy.
Results showed that there was a sustained reduction in intravascular
hemolysis, as measured by lactate dehydrogenase (LDH), through the 38
weeks of treatment. LDH decreased 87% from a median of 1,814 U/L at
baseline to a median of 232 U/L at 38 weeks of treatment (p<0.001).
A significant improvement in chronic kidney disease (CKD) stage was also
seen in Japanese patients on long-term Soliris treatment. Two-thirds
(19/29) of patients enrolled in the AEGIS study demonstrated evidence of
CKD at baseline prior to eculizumab. At week 38, 33% (9/27) of patients
showed improvement in CKD while 67% (18/27) showed no change from
baseline and no patients (0%) worsened (p<0.05). Further, 53% (9/17) of
patients with CKD at baseline demonstrated improvement. Among the 9
patients who showed improvement, 8 had stage 1-2 CKD at baseline and one
had stage 3-5 at baseline.
Soliris treatment continued to appear to be safe and well-tolerated in
treated patients during the initial 26-weeks of the extension study.
Four patients experienced 9 serious adverse events (SAEs); one patient
experienced 4 SAEs that were reported as probably or possibly related to
the drug. Most adverse events (AEs) were mild in severity. The most
frequent AEs were nasopharyngitis (52%), headache (19%), blood alkaline
phosphatase increases (19%) and anemia (11%). No thrombotic events or
meningococcal infections were reported during Soliris treatment.