Apellis Pharmaceuticals Announces that All Four Severely Anemic Soliris™-Treated Patients with Paroxysmal Nocturnal Hemoglo...
September 04 2018 - 7:30AM
PHAROAH Trial Results to-Date Show APL-2
Monotherapy Eliminated Transfusion Dependency and Improved Markers
of Anemia in PNH Patients on Soliris™
Apellis Pharmaceuticals, Inc. (Nasdaq:APLS), a clinical-stage
biopharmaceutical company focused on the development of novel
therapeutic compounds to treat disease through the inhibition of
the complement system, today announced an update on its US-based
Phase 1b PHAROAH trial for patients with paroxysmal nocturnal
hemoglobinuria (PNH). The ongoing PHAROAH trial is evaluating
treatment with APL-2, a novel inhibitor of complement factor C3, in
patients on treatment with eculizumab (Soliris™) who are severely
anemic and transfusion-dependent.
Patients enrolled in the PHAROAH trial were
initially co-treated with APL-2 and eculizumab, with the potential
for discontinuation of eculizumab at the discretion of the treating
physician. Two of the six patients were removed from treatment with
APL-2 due to pregnancy and BMI-associated comorbidities. Four of
the six patients continued in the study for more than 32 weeks. In
these four patients, co-treatment with APL-2 resulted in an
improvement of hemoglobin levels and other markers for anemia and
none of the four patients required a transfusion during the
co-treatment period with eculizumab, which ranged from 17 to 20
months. Earlier this year Apellis announced that three of the four
patients discontinued treatment with eculizumab and were continuing
to receive APL-2. The fourth patient has now discontinued treatment
with eculizumab and is continuing to receive APL-2. All four
patients have improved hemoglobin and reticulocytes as compared to
the baseline established with eculizumab monotherapy and have
achieved lactate dehydrogenase (LDH) levels below the upper limit
of normal (ULN).
|
|
Eculizumab Monotherapyi |
APL-2 + Eculizumabii |
APL-2 Monotherapyiii |
Hemoglobin (g/dL)* |
8.9 |
11.9 |
11.4 |
Annual Transfusions (avg.) |
6.0 |
0 |
0 |
LDH (ULN)* |
1.0x |
0.8x |
0.9x |
Reticulocytes (ULN)* |
2.7x |
1.2x |
0.8x |
Patient Years (Total) |
NA |
5.9 Years |
1.9 Years |
Multiple of Eculizumab Label Dose (900mgx2wk.) |
1.6x |
1.0x |
- |
*Average
last available reading for all four patients on each dosing
regimen(i) last reading during eculizumab monotherapy prior to
co-treatment with APL-2(ii) last reading during co-treatment and
prior to APL-2 monotherapy(iii) last reading while on APL-2
monotherapy |
|
“By eliminating transfusion dependency and improving markers of
anemia in patients in the study, APL-2 has given these patients a
meaningful clinical benefit over eculizumab monotherapy,” said Dr.
Cedric Francois, M.D., Ph.D., co-founder and CEO of Apellis. “This
is precisely the benefit that we are aiming to confirm in our
ongoing PEGASUS Phase 3 head-to-head trial against eculizumab.”
In addition to the PHAROAH trial and the ongoing Phase 3
head-to-head trial against eculizumab, APL-2 is also being
evaluated in the PADDOCK Phase 1b trial in treatment naïve
patients. Apellis previously reported that the patients in the
PADDOCK trial experienced a mean 3.5 g/dL improvement in hemoglobin
and an average reduction in LDH to within the normal range after
daily subcutaneous administration of APL-2 for at least 28
days.
To date, subcutaneous APL-2 has been well-tolerated with
cumulative systemic exposure of over 18 patient years of treatment
on APL-2. No significant infections or thromboembolic events have
been observed.
About Paroxysmal Nocturnal
HemoglobinuriaParoxysmal 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 the PHAROAH Trial PHAROAH is an ongoing
open label safety and efficacy study of 270 mg of APL-2
administered daily by subcutaneous injection as a complementary
therapy to patients with PNH who continue to be anemic (Hb <10
g/dL at screening or have a history of at least one transfusion in
the previous year) despite treatment with eculizumab. The PHAROAH
study was initiated in November 2014 and is being conducted at
multiple clinical sites in the United States.
About the PEGASUS Phase 3 TrialPEGASUS is a
70-patient, randomized, head-to-head study comparing APL-2
monotherapy to eculizumab monotherapy in patients currently on
treatment with eculizumab who have a hemoglobin level <10.5
g/dL, regardless of eculizumab dose or transfusion history.
Patients will be co-treated for 4 weeks with twice weekly
subcutaneous infusions of 1080 mg of APL-2 alongside their existing
eculizumab regimen and then randomized 1:1 to either APL-2
monotherapy or eculizumab monotherapy and monitored for 56
weeks. The primary endpoint will be change in hemoglobin from
baseline to Week 16. Secondary endpoints include change from
baseline to Week 16 in absolute reticulocyte count, LDH levels and
FACIT-fatigue score. The number of packed red blood cell
units transfused from Week 4 to 16 will also be compared.
About APL-2 APL-2 is designed to inhibit
the complement cascade centrally at C3 and may have the potential
to treat a wide range of complement-mediated diseases more
effectively than is possible with partial inhibitors of complement.
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). In addition to the PHAROAH
trial, Apellis is currently evaluating APL-2 in a head-to-head
Phase 3 clinical trial for systemic administration comparing APL-2
to Soliris in PNH patients with hemoglobin levels less than
10.5g/dL (the PEGASUS trial) and a Phase 1b clinical trial for
systemic administration in treatment naïve PNH patients (the
PADDOCK trial). Apellis is also testing APL-2 for systemic
administration in a Phase 2 clinical trial in autoimmune hemolytic
anemia (AIHA) and a Phase 2 clinical trial in complement dependent
nephropathies, as well as a Phase 1b/2 clinical trial evaluating
intravitreal APL-2 in wet age-related macular degeneration.
Phase 3 studies are planned for APL-2 via intravitreal
administration for geographic atrophy (GA). Future clinical
studies of APL-2 are anticipated in PNH and other diseases in which
complement is implicated.
About Apellis Apellis Pharmaceuticals,
Inc. is a clinical-stage biopharmaceutical company focused on
the development of novel therapeutic compounds for the treatment of
a broad range of life-threatening or debilitating autoimmune
diseases based upon complement immunotherapy through the inhibition
of the complement system at the level of C3. Apellis is the first
company to advance chronic therapy with a C3 inhibitor into
clinical trials. For additional information about Apellis and
APL-2, please visit http://www.apellis.com.
Forward-Looking Statements
Statements in this press release about future expectations,
plans and prospects, as well as any other statements regarding
matters that are not historical facts, may constitute
“forward-looking statements” within the meaning of The Private
Securities Litigation Reform Act of 1995. These statements include,
but are not limited to, statements relating to the implications of
preliminary clinical data. The words “anticipate,” “believe,”
“continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,”
“potential,” “predict,” “project,” “should,” “target,” “will,”
“would” and similar expressions are intended to identify
forward-looking statements, although not all forward-looking
statements contain these identifying words. Actual results may
differ materially from those indicated by such forward-looking
statements as a result of various important factors, including:
whether preliminary or interim results from a clinical trial such
as the results reported in this release will be predictive of the
final results of the trial; whether results obtained in preclinical
studies and clinical trials will be indicative of results that will
be generated in future clinical trials; whether APL-2 will
successfully advance through the clinical trial process on a timely
basis, or at all; whether the results of such clinical trials will
warrant regulatory submissions and whether APL-2 will receive
approval from the United States Food and Drug
Administration or equivalent foreign regulatory agencies for
GA, PNH or any other indication; whether, if Apellis’ products
receive approval, they will be successfully distributed and
marketed; and other factors discussed in the “Risk Factors” section
of Apellis’ Quarterly Report on Form 10-Q filed with
the Securities and Exchange Commission on July 31,
2018 and the risks described in other filings that Apellis may make
with the Securities and Exchange Commission. Any
forward-looking statements contained in this press release speak
only as of the date hereof, and Apellis specifically
disclaims any obligation to update any forward-looking statement,
whether as a result of new information, future events or
otherwise.
Media Contact: Tully
Nicholas tnicholas@denterlein.com 617.482.0042 (office)
860.490.0218 (mobile)
Investor Contact: Alex
Kaneakane@w2ogroup.com212.301.7218 (office) 929.400.2691
(mobile)
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