LOUISVILLE, Ky., June 29, 2017 /PRNewswire/ -- Apellis
Pharmaceuticals, Inc. today provided an update on clinical outcomes
in its two ongoing Phase 1b clinical trials with APL-2, a
complement C3 inhibitor, in the treatment of patients with
paroxysmal nocturnal hemoglobinuria (PNH). PNH is a rare, acquired,
potentially life-threatening disease characterized by
complement-mediated hemolytic anemia. Apellis is developing APL-2
as a next generation monotherapy, with the goal of resolving anemia
and transfusion dependency in PNH patients on standard of care.
APL-2 is being developed for newly diagnosed PNH patients as
well as for patients who suffer from anemia while receiving
standard of care intravenous infusions of eculizumab. Eculizumab is
a complement C5 inhibitor that improves anemia in patients with
PNH, but leaves up to 75% of PNH patients anemic and 35-40%
transfusion-dependent.
APL-2 is being evaluated in two Phase 1b clinical trials.
PADDOCK is an open label safety and efficacy study of 270mg of
APL-2 administered daily by subcutaneous injection to PNH patients
(n=3) who have never received eculizumab. In PADDOCK, in the first
month, all three patients treated with APL-2 monotherapy
experienced rapid corrections in lactate dehydrogenase (LDH), a key
marker of hemolytic activity in PNH, from an average of 1,615 U/L
to an average of 275 U/L (1.1x upper limit of normal), a decline of
83%.
PHAROAH is an open label safety and efficacy study of 270mg of
APL-2 administered daily by subcutaneous injection as a
complementary therapy to suboptimal responders to eculizumab (n=6),
defined as hemoglobin levels (Hb) of less than 10 g/dL at screening
or a history of at least one transfusion in the previous year. In
the first month, average Hb levels in the six patients increased
from 8.8 g/dL to 11.9 g/dL, an increase of 36%. During this
period, patients also experienced rapid corrections in LDH from an
average of 280 U/L (1.3x upper limit of normal) to an average of
163 U/L (0.8x upper limit of normal), a decline of 42%. After six
months, the average Hb level was 11.4 g/dL, and the average
LDH level continued to be normal at 184 U/L (0.9x upper limit of
normal). During that same period, the average transfusion rate
dropped from 3.4/month on eculizumab monotherapy to 0.3/month when
APL-2 was added to eculizumab. Notably, five of six patients on
baseline were receiving higher than normal dosing with eculizumab
in the form of 1,200 mg every two weeks or 900 mg every week, as
opposed to the normal 900 mg every two weeks.
There have been no significant drug-related safety concerns and
overall APL-2 was well tolerated in both PADDOCK and PHAROAH during
the six months of dosing. None of the patients experienced episodes
of breakthrough hemolysis, which can occur in patients treated with
C5 inhibitors. Both open label studies are ongoing and are designed
to support cross-over from eculizumab to APL-2 after a brief period
of add-on dosing. Later in 2017, the Company plans to switch from
daily to twice per week dosing.
Cedric Francois, M.D., Ph.D.,
chief executive officer of Apellis, said: "We are very encouraged
by the robust hemoglobin improvements and LDH corrections observed
in PNH patients treated with APL-2, which we are developing as a
monotherapy alternative to eculizumab and other C5 inhibitors. We
believe that C3-inhibitor APL-2 can be the next generation PNH
treatment offering patients a powerful solution to meaningfully
improve their quality of life."
Dr. Peter Hillmen, Professor of
Experimental Haematology, University of Leeds, Leeds,
UK, added: "The initial results from the APL-2 studies are
encouraging in terms of both safety and effectiveness. The unique
mode of action of APL-2 promises to improve the treatment for
patients with PNH who have a sub-optimal response to
eculizumab."
Phase 3 initiation is planned for Q4/2017.
About Paroxysmal Nocturnal Hemoglobinuria
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired,
potentially life-threatening disease characterized by
complement-mediated hemolysis with or without hemoglobinuria, an
increased susceptibility to thrombotic episodes and/or some degree
of bone marrow dysfunction. A significant subset of patients
treated with the current standard of care still suffer from
debilitating anemia and transfusion dependence.
About APL-2
APL-2 is a synthetic cyclic peptide conjugated to a polyethylene
glycol (PEG) polymer that binds specifically to C3 and C3b,
effectively blocking all three pathways of complement activation
(classical, lectin, and alternative) with a particularly high
potency against the alternative pathway. This comprehensive
inhibition of complement-mediated pathology may have the potential
to control symptoms and modify underlying disease in patients
suffering from PNH.
About Apellis
Apellis is a clinical-stage biopharmaceutical company focused on
the development of a platform of novel therapeutic compounds for
the treatment of a broad range of autoimmune diseases based upon
complement immunotherapy. Uncontrolled complement activation can
lead to a wide range of life-threatening or debilitating disorders.
Apellis is the first company to advance chronic therapy with a C3
inhibitor into clinical trials. Apellis is currently evaluating its
lead product candidates in Phase 1 clinical trials in paroxysmal
nocturnal hemoglobinuria (PNH) and in a Phase 2 clinical trial in
geographic atrophy, the advanced form of dry age-related macular
degeneration (AMD). For additional information about Apellis,
please visit www.apellis.com.