Celldex Therapeutics, Inc. (NASDAQ:CLDX) today announced interim
data from the Company’s ongoing Phase 1b clinical trial of
barzolvolimab in patients with moderate to severe chronic
spontaneous urticaria (CSU) refractory to antihistamines.
Barzolvolimab is a humanized monoclonal antibody that specifically
binds the receptor tyrosine kinase KIT with high specificity and
potently inhibits its activity, which is required for mast cell
function and survival. CSU is characterized by the occurrence of
hives or wheals for 6 weeks or longer without identifiable specific
triggers or causes.
Data show that multiple doses of barzolvolimab resulted in
dose-dependent decreases in itch and hives, as measured through the
urticaria activity score over 7 days (UAS7), with a mean UAS7
reduction of 66.6% in all patients in the 1.5 mg/kg dose group
(n=8) at week 12 and 75.1% in all patients in the ongoing 3.0 mg/kg
dose group (n=9) at week 8 (reflects one dose), demonstrating
meaningful symptom improvements for patients. Complete response as
measured by UAS7=0 was 57.1% for patients in the 1.5 mg/kg dose
group at week 12 and 44.4% for the patients in the 3.0 mg/kg dose
group at week 8 (reflects one dose; ongoing).
Importantly, administering multiple doses of barzolvolimab
demonstrated a favorable safety profile, supporting Phase 2
clinical development. These data were presented by Dr. Marcus
Maurer, Professor of Dermatology and Allergy at Charité –
Universitätsmedizin in Berlin, as a late-breaking
electronic poster presentation (#100097) as part of
the European Academy of Allergy and Clinical Immunology
(EAACI) Annual Congress 2022.
“We are excited by these interim multiple dose data which
demonstrate strong clinical activity, rapid onset and sustained
durability with a well-tolerated safety profile, including in
patients with prior omalizumab experience,” commented Anthony
S. Marucci, President and Chief Executive Officer of Celldex
Therapeutics. “We believe these impressive early data further
demonstrate barzolvolimab’s unique mechanism and its potential to
provide meaningful symptom relief to patients suffering from
diseases driven by mast cells. These data support the continued
development of barzolvolimab, including our recently initiated
Phase 2 chronic urticaria studies.”
“These remarkable early results confirm that chronic urticaria
is driven by mast cells and barzolvolimab has again demonstrated
its ability to bring meaningful improvements to patients suffering
from these often very severe and debilitating diseases,”
said Marcus Maurer, M.D., Professor of Dermatology and Allergy
at Charité – Universitätsmedizin in Berlin and a lead
investigator on the study. “There are extensive numbers of patients
globally with CSU who cannot be helped at all with the current
standard of care, so barzolvolimab would represent a considerable
advance in the treatment landscape for these patients and
potentially other diseases with mast cell involvement.”
Summary of Data from Ongoing Phase 1b CSU Trial of
Barzolvolimab
As of the data cut-off on May 23, 2022, 34 patients with CSU
were enrolled and treated [26 barzolvolimab (n=9 in 0.5 mg/kg; n=8
in 1.5 mg/kg; n=9 in 3.0 mg/kg) and 8 placebo]. The 0.5 mg/kg and
1.5 mg/kg cohorts had completed study participation through 24
weeks; 7 of 12 patients in the 3.0 mg/kg cohort had completed week
12; enrollment in the 4.5 mg/kg cohort was ongoing. Adverse events
through data cutoff and hematology data through week 12 were
included for all dose groups; clinical activity and tryptase data
were included through week 12 for 0.5 mg/kg and 1.5 mg/kg, and
through week 8 for 3 mg/kg (ongoing; reflecting the administration
of only one dose).
Interim Clinical Activity Results
- Barzolvolimab
results in rapid, marked and durable responses in patients with
moderate to severe CSU refractory to antihistamines, including
patients with prior omalizumab treatment.
- Mean reduction from
baseline in urticaria activity (UAS7) of 66.6% in all patients in
the 1.5 mg/kg dose group (n=8) at week 12 and 75.1% in all patients
in the 3.0 mg/kg dose group (n=9) at week 8 (reflects one dose;
ongoing), demonstrating clinically meaningful symptom improvements
for patients.
- Complete response
(UAS7=0) of 57.1% in the 1.5 mg/kg dose group at week 12 and 44.4%
at week 8 (reflects one dose; ongoing) in the 3 mg/kg dose group
which is a key therapeutic goal.
- 75% well-controlled
disease by Urticaria Control Test (UCT) in the 1.5 mg/kg dose group
at week 12 and 83.3% in the 3 mg/kg dose group at week 8 (reflects
one dose; ongoing).
- Patients with prior
omalizumab therapy had similar symptom improvement as all
patients.
- All three doses of
barzolvolimab markedly improved urticaria symptoms and disease
control, with rapid improvement in itch and hives. As predicted,
the lowest dose of 0.5 mg/kg resulted in suboptimal clinical
activity compared to the higher doses.
- Rapid onset of
responses after initial dosing and sustained durability were
observed; onset as early as 1 week after the first dose.
- Tryptase
suppression, indicative of mast cell depletion, paralleled symptom
improvement, demonstrating the impact of mast cell depletion on CSU
disease activity.
Summary of Clinical Activity Assessments at week 12 for 0.5
mg/kg and 1.5 mg/kg dose groups and week 8 for 3.0 mg/kg dose group
(ongoing, clinical activity reflects one dose):
All Patients |
0.5 mg/kgQ4Wat Week
12 |
1.5 mg/kgQ4Wat Week
12 |
3.0 mg/kgQ8Wat Week
8(ongoing) |
Placeboat Week 12/8 |
UAS7 Changes |
Mean Score Change in UAS7 From Baseline |
-11.1 |
-18.1 |
-22.7 |
-14.3 / -12.4 |
Mean % Change in UAS7 From Baseline |
-39.7% |
-66.6% |
-75.1% |
-35.9% / -31.1% |
Clinical Responses |
UAS7=0 (Complete Response) |
11.1% |
57.1% |
44.4% |
16.7% / 0% |
UAS7 ≤ 6 (Well-controlled) |
22.2% |
57.1% |
55.6% |
16.7% / 0% |
UCT ≥ 12 (Well-controlled) |
12.5% |
75.0% |
83.3% |
16.7% / 0% |
The UAS7 score is calculated as the sum over 7 days of the daily
intensity of itch (ISS7 itch severity score) and number of hives
(HSS7 hives severity score). UAS7 values range from 0 to 42, with
higher values reflecting higher disease activity. UCT has 4 items
with 5 answer options (scored with 0-4 points); recall period of 4
weeks. Low points indicate high disease activity and low disease
control. The minimum and maximum UCT scores are 0 and 16, with 16
points indicating complete disease control and ≥12 indicating well
controlled disease.
Safety Results
- Barzolvolimab was well tolerated with a favorable safety
profile; effects of multiple dose administration were consistent
with observations in single dose studies.
- Most AEs were mild
or moderate in severity and resolved while on study, with none
leading to treatment discontinuation. The most common treatment
emergent adverse events were urinary tract infections, headache,
neutropenia and back pain. UTIs, headache and backpain were all
reported as unrelated to treatment. There was one severe adverse
event of salmonella gastroenteritis which was also not related to
study therapy.
- Changes in hematologic parameters were consistent with
observations in single dose studies, with no pattern of further
decreases with multiple doses; hematologic values generally
remained within the normal range. Four patients with screening and
baseline neutrophil counts at the lower end of the normal range on
study initiation had decreases in neutrophil counts reported as
AEs. The pattern observed in the neutrophil changes for these
patients was similar to the pattern seen in patients across the
barzolvolimab program to date—generally transient, asymptomatic,
and mild.
The Phase 1b study is a randomized, double-blind,
placebo-controlled clinical trial designed to assess the safety of
multiple ascending doses of barzolvolimab in patients with moderate
to severe CSU who remain symptomatic despite treatment with
antihistamines. Secondary and exploratory objectives include
pharmacokinetic and pharmacodynamic assessments, including
measurement of tryptase and stem cell factor levels and clinical
activity outcomes (impact on urticaria symptoms, disease control,
clinical response) as well as quality of life assessments. The
study is expected to enroll approximately 40 patients with CSU
across four cohorts (8 barzolvolimab; 2 placebo). Barzolvolimab is
administered intravenously at 0.5 mg/kg mg every 4 weeks, 1.5 mg/kg
every 4 weeks, 3 mg/kg every 8 weeks, 4.5 mg/kg every 8 weeks, as
add-on treatment to H1-antihistamines, either alone or in
combination with H2-antihistamines and/or leukotriene receptor
agonists. For additional information on this trial (NCT04538794),
please visit www.clinicaltrials.gov.
Webcast and Conference CallThe Company will
host a conference call/webcast along with Dr. Marcus Maurer to
discuss the results at 6:30 p.m. ET on Thursday, June 30. The event
will be webcast live and can be accessed by going to the "Events
& Presentations" page under the "Investors & Media" section
of the Celldex Therapeutics website at www.celldex.com. The call
can also be accessed by dialing (866) 743-9666 (within the United
States) or (760) 298-5103 (outside the United States). The
conference ID is 6130457. A replay of the call will be archived on
the Company's website or can be accessed by dialing (855) 859-2056
(within the United States) or (404) 537-3406 (outside the United
States). The conference ID is 6130457.
About Chronic Spontaneous Urticaria (CSU)CSU is
characterized by the occurrence of hives or wheals for 6 weeks or
longer without identifiable specific triggers or causes. The
activation of the mast cells in the skin (release of histamines,
leukotrienes, chemokines) results in episodes of itchy hives,
swelling and inflammation of the skin that can go on for years or
even decades. Current therapies provide symptomatic relief only in
some patients.
About BarzolvolimabBarzolvolimab (also referred
to as CDX-0159) is a humanized monoclonal antibody that
specifically binds the receptor tyrosine kinase KIT with high
specificity and potently inhibits its activity. KIT is expressed in
a variety of cells, including mast cells, which mediate
inflammatory responses such as hypersensitivity and allergic
reactions. KIT signaling controls the differentiation, tissue
recruitment, survival and activity of mast cells. In certain
inflammatory diseases, such as chronic urticaria, mast cell
activation plays a central role in the onset and progression of the
disease.
About Celldex Therapeutics, Inc.Celldex is a
clinical stage biotechnology company dedicated to developing
monoclonal and bispecific antibodies that address devastating
diseases for which available treatments are inadequate. Our
pipeline includes antibody-based therapeutics which have the
ability to engage the human immune system and/or directly affect
critical pathways to improve the lives of patients with
inflammatory diseases and many forms of cancer. Visit
www.celldex.com.
Forward Looking Statement This release contains
"forward-looking statements" made pursuant to the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.
These statements are typically preceded by words such as
"believes," "expects," "anticipates," "intends," "will," "may,"
"should," or similar expressions. These forward-looking statements
reflect management's current knowledge, assumptions, judgment and
expectations regarding future performance or events. Although
management believes that the expectations reflected in such
statements are reasonable, they give no assurance that such
expectations will prove to be correct or that those goals will be
achieved, and you should be aware that actual results could differ
materially from those contained in the forward-looking statements.
Forward-looking statements are subject to a number of risks and
uncertainties, including, but not limited to, our ability to
successfully complete research and further development and
commercialization of Company drug candidates, including
barzolvolimab (also referred to as CDX-0159), in current or future
indications; the uncertainties inherent in clinical testing and
accruing patients for clinical trials; our limited experience in
bringing programs through Phase 3 clinical trials; our ability to
manage and successfully complete multiple clinical trials and the
research and development efforts for our multiple products at
varying stages of development; the effects of the outbreak of
COVID-19 on our business and results of operations; the
availability, cost, delivery and quality of clinical materials
produced by our own manufacturing facility or supplied by contract
manufacturers, who may be our sole source of supply; the timing,
cost and uncertainty of obtaining regulatory approvals; the failure
of the market for the Company's programs to continue to develop;
our ability to protect the Company's intellectual property; the
loss of any executive officers or key personnel or consultants;
competition; changes in the regulatory landscape or the imposition
of regulations that affect the Company's products; our ability to
continue to obtain capital to meet our long-term liquidity needs on
acceptable terms, or at all, including the additional capital which
will be necessary to complete the clinical trials that we have
initiated or plan to initiate; and other factors listed under "Risk
Factors" in our annual report on Form 10-K and quarterly reports on
Form 10-Q.
All forward-looking statements are expressly qualified in their
entirety by this cautionary notice. You are cautioned not to place
undue reliance on any forward-looking statements, which speak only
as of the date of this release. We have no obligation, and
expressly disclaim any obligation, to update, revise or correct any
of the forward-looking statements, whether as a result of new
information, future events or otherwise.
Company ContactSarah CavanaughSenior Vice
President, Corporate Affairs & Administration(508)
864-8337scavanaugh@celldex.com
Patrick TillSenior Director, Investor Relations & Corporate
Communications(484) 788-8560ptill@celldex.com
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