Diamyd presents detailed results of European Phase III study
Diamyd Medical AB reports detailed results from the Company's European
Phase III study of the antigen-based diabetes therapy Diamyd®, which, as
previously announced, did not meet the primary efficacy endpoint.
Today, June 28, at the “American Diabetes Association's 71st Scientific
Sessions” in San Diego, California, USA, lead investigator Dr. Johnny
Ludvigsson presents the detailed results of Diamyd Medical's European
Phase III study of the antigen-based diabetes therapy Diamyd®.
The study enrolled 334 patients, 10 to 20 years old, who were diagnosed
with type 1 diabetes within three months of entering the study. All of
the patients had some endogenous insulin production left and were GAD
antibody positive at study entry. The study included three treatment
arms in which a third of the patients received four subcutaneous
injections of Diamyd® (day 1, 30, 90 and 270), one third received two
injections of Diamyd®, and one third received placebo (non-active
substance). Patients were followed for 15 months. Diamyd® was well
tolerated, as demonstrated by a similar number of adverse events
reported in the groups treated with Diamyd® and the placebo group. The
levels of GAD antibodies increased significantly in the groups receiving
Diamyd®, but not in the placebo group.
The primary efficacy endpoint was change in C-peptide, a measure of
endogenous insulin production, between the first study visit and the
visit 15 months later. In the study, the levels of C-peptide decreased
similarly in all treatment groups and, as previously reported, the
primary efficacy endpoint was not met, although a small positive effect
was seen. Patients treated with Diamyd® had on average 16.4 percent more
remaining C-peptide at 15 months compared to those who received placebo.
The p-value of the primary endpoint was 0.10. The secondary efficacy
endpoints included mean daily dose of insulin, hemoglobin A1c (HbA1c)
and frequency of hypoglycemia. Treatment with Diamyd® did not achieve a
statistically significant effect for any secondary endpoint.
“I am naturally disappointed over the outcome of the study and surprised
that we did not see a greater overall effect given previous studies,”
said Dr. Johnny Ludvigsson, lead investigator and professor at Linköping
University. “However, we cannot reject this treatment based on the fact
that this study did not reach statistical significance. We must learn
from other therapeutic areas, like allergy and cancer, which have
advanced by combining different treatments, each of which may have
limited effect. It is also possible that the treatment is effective in
prevention of type 1 diabetes.”
Pre-specified subgroup analyses suggest that Diamyd® had an effect in
several subgroups. These analyses included divisions based on gender,
age, country, number of days since diagnosis at baseline and other
characteristics. In the subgroup of male study participants the patients
treated with Diamyd® kept 41 percent more of their C-peptide than those
who received placebo (p <0.01).
“Although subgroup analyses must be interpreted with great caution and
require confirmation in other studies, our results indicate that Diamyd®
and the active ingredient GAD65 may preserve the body's own insulin
production in certain subgroups of patients,” says Dr. Ludvigsson.
Another interesting observation was that among the patients who received
their first injection of Diamyd® during the period March-April, the
patients treated with Diamyd® kept significantly more of their C-peptide
than the corresponding placebo-treated patients (p = 0.02). In the
previous Phase II study with Diamyd®, all study participants received
their first injection of study drug during these months and since there
are seasonal variations in the immune system this may play a role for
the treatment's effect on the immune system. Another factor that could
contribute to the difference in outcomes between Phase II and Phase III
is the use of influenza vaccine during the study periods. During the
Phase III study, there was a pandemic influenza outbreak that led to
many vaccinations in the study even though, originally, it was not
planned to allow for influenza vaccination in conjunction with
injections of study drug. Among the patients who were not vaccinated
against influenza within 150 days after the first injection of Diamyd®
or placebo, the p-value was 0.07.
Given that the European Phase III study did not meet the primary
efficacy endpoint, Diamyd Medical decided not to complete the follow-up
period of the study, which therefore was closed on June 1 this year. On
June 23 the Company announced the decision to suspend dosing in a
parallel US Phase III study and to also initiate closure of that study.
For more information, please contact:
Peter Zerhouni, Acting President and CEO Diamyd Medical AB (publ.)
Phone: 46 8 661 0026
For press material, please contact:
Andreas Ericsson, Diamyd Medical AB (publ.)
press@diamyd.com (press@diamyd.com)
Phone: 46 8 661 0026
