Severely anemic patients with PNH on treatment
with Soliris™ can become transfusion-free with improved
hemoglobin when switched to APL-2 monotherapy
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, will provide clinical updates today on its
two ongoing Phase Ib PNH studies during an R&D Day in New York
between 2.00 pm and 5.00 pm.
Apellis is developing APL-2 for the treatment of PNH, a rare,
acquired, potentially life-threatening disease characterized by
complement-mediated thrombosis and hemolytic anemia. The
Company believes that by targeting C3, APL-2 can improve
hematological parameters in patients with PNH on treatment with C5
inhibitors such as eculizumab (Soliris™). Specifically, the
Company believes that APL-2 has the potential to significantly
improve hemoglobin (Hb) levels in eculizumab-treated patients
suffering from anemia. In a recent study, up to 70% of
patients treated with eculizumab, the only currently approved
therapy for PNH, were anemic, with hemoglobin levels below 12.0
g/dL.1 Apellis’ clinical PNH program is designed to allow
patients with PNH to switch from eculizumab to APL-2 monotherapy
after one month of co-treatment with the goal of improving
hematological parameters, particularly hemoglobin.
Apellis has two ongoing Phase Ib proof-of-concept clinical
trials evaluating APL-2 in PNH: PHAROAH and PADDOCK. The
PHAROAH trial is evaluating whether APL-2 can provide benefits to
patients on treatment with eculizumab who are severely anemic and
transfusion-dependent. Patients have been treated with APL-2
in addition to eculizumab and several patients have been switched
to APL-2 monotherapy after at least a year of co-treatment.
The PADDOCK trial is evaluating the safety and efficacy of APL-2 in
patients with PNH not previously treated with eculizumab.
PHAROAH Trial UpdateThe 32 week data for the
trial were released last December at the International PNH Interest
Group meeting, with six patients enrolled to receive co-treatment
of eculizumab and APL-2 at 270 mg/day. The four patients who
remained in the study (as of week 32) have remained in the study
for an average of 92 weeks. Key findings include:
- No transfusions needed: The average Hb for the four patients
before starting combined dosing with APL-2 was 8.9 g/dL.
These patients received an average of 6.0 transfusions on
eculizumab in the 52 weeks before co-treatment with APL-2.
Since commencing co-treatment with APL-2, including and since
the weaning from eculizumab, there have been no transfusions in any
of the four patients.
- Successful reduction in dosing of eculizumab: At baseline,
three of the four patients were on higher than label dose (900 mg
every 2 weeks) of eculizumab. During the evaluation period,
the treating physicians reduced dosing with eculizumab to label
dose in all four patients without hematological impact.
- Successful weaning from eculizumab: Three of the four patients
have thus far been weaned from eculizumab and treated with APL-2
monotherapy for 7, 23 and 30 weeks. Following weaning, all
three patients remained hematologically stable with no transfusions
and stable average hemoglobin of 11.8 g/dL at most recent measure
(normal Hb >12.0 g/dL). This represents an average
hemoglobin increase of 2.3 g/dL from the baseline established with
eculizumab monotherapy. All three patients have also
maintained lactate dehydrogenase (LDH) in the normal range, with an
average last measure of 0.76x upper limit of normal (ULN).
The fourth patient, with a BMI of 46, was hematologically
stable when the dose of eculizumab was reduced from twice label to
normal label dose but showed elevated LDH levels when eculizumab
was discontinued completely, leading to a restart with
eculizumab. Since biomarkers suggested under-dosing, the dose
of APL-2 will be increased before attempting to wean from
eculizumab treatment again. At last measure, on APL-2 and
label eculizumab dose, this patient had a hemoglobin of 11.3 g/dL
vs. a baseline of 7.0 g/dL when the patient received twice the
label dose of eculizumab and required 9 transfusions in the prior
52 weeks. This change in Hb represents an increase of 4.3
g/dL compared to baseline as well as zero transfusions in the 87
weeks on co-treatment with APL-2.
“It was initially very encouraging to see
the significant improvement in
these significantly anemic patients when APL-2 was added
to Soliris™,” said Anita Hill, Lead Consultant for the
National PNH Service at the Leeds Teaching Hospitals,
U.K. “To see APL-2 maintain the same
hematological benefits when dosing with Soliris™ was reduced
in all and weaned entirely in three of four patients is
impressive.”
PADDOCK Trial UpdateIn April 2018, the Company
reported that APL-2 increased Hb levels and reduced LDH in eight
patients not previously treated with eculizumab after daily
subcutaneous administration with 270 mg/day of APL-2 for at least
28 days. Five additional patients have been enrolled and are
evaluable for at least 28 days. At baseline, the average
hemoglobin level for the 13 patients was 8.4 g/dL and average LDH
level was 9.5x ULN. As of June 19th, 2018, eight patients
have been on APL-2 for over 8 weeks and 4 have reached 16 weeks of
treatment. Key findings include:
- Improved hemoglobin and other anemia markers: In the last
reading, the average Hb from each patient on APL-2 was 11.9 g/dL,
an increase of 3.5 g/dL over baseline. Average bilirubin and
reticulocytes, which are markers for anemia, were in the normal
range. Two total transfusions were given in the study, one at
day two in one patient and one at day 14 in a non-compliant
patient; it is believed that neither patient had yet reached
sufficient exposure to APL-2 for hematological benefit.
- Improved LDH: The average LDH level at week 4 was 0.8x ULN and
has remained within the normal range beyond week 4.
“The data generated by APL-2 in treatment-naïve patients with
PNH are impressive compared to our experience with
Soliris™,” said Dr. Peter Hillmen, Professor of Experimental
Hematology, University of Leeds, Leeds, UK. “The early
experience of APL-2 demonstrates that inhibiting C3
controls extravascular as well as intravascular
hemolysis unlike inhibition of C5 where continued
extravascular hemolysis is frequently problematic.”
“We are especially pleased to see APL-2 monotherapy helping a
range of patients, including those who are severely anemic and
continue to suffer while being treated with high doses of
eculizumab,” said Dr. Cedric Francois, M.D., Ph.D., co-founder and
CEO of Apellis. “We are encouraged by these data that support our
belief that many rare and autoimmune conditions can be treated
through C3 inhibition, and we look forward to having Dr. Hillmen
and Dr. Hill present the detailed results at our R&D Day
today.”
To date, subcutaneous APL-2 has generally been well-tolerated
with cumulative systemic exposure of over 12 patient years of
treatment on APL-2. No significant infections or
thromboembolic events have been observed.
The live webcast and slide presentation for the R&D Day may
be accessed by visiting the “Events and Presentations” page of the
“Investors and Media” section of the Company’s website at
http://www.apellis.com. Replay of the webcast will be
available for 90 days following the event.
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 PADDOCK trial PADDOCK is an
ongoing open-label Phase Ib safety and efficacy study of 270 mg of
APL-2 administered daily by subcutaneous injection to patients with
PNH who have never received eculizumab. The PADDOCK study was
initiated in December 2015 and is being conducted at multiple
clinical sites outside of the United States.
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). Apellis is currently
evaluating APL-2 in two Phase Ib clinical trials for systemic
administration in paroxysmal nocturnal hemoglobinuria (the PHAROAH
trial and the PADDOCK trial). Apellis is also testing APL-2
for systemic administration in a Phase II clinical trial in
autoimmune hemolytic anemia (AIHA) and a Phase II clinical trial in
complement dependent nephropathies, as well as a Phase Ib/II
clinical trial evaluating intravitreal APL-2 in wet age-related
macular degeneration. Phase III studies are planned in
intravitreal APL-2 for geographic atrophy (GA) and PNH.
Future clinical studies of APL-2 are anticipated in 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 April 30, 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 Kane
akane@w2ogroup.com 212.301.7218 (office) 929.400.2691 (mobile)
1 McKinley CE, Richards SJ, Munir T, et al. Extravascular
Hemolysis Due to C3-Loading in Patients with PNH Treated with
Eculizumab: Defining the Clinical Syndrome. Blood (ASH Annual
Meeting Abstracts) 2017;130(S1):3471.
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