- Exploratory biomarker analyses suggest
possible cardiac disease improvements and renal response -
Caelum Biosciences and Alexion Pharmaceuticals, Inc.
(NASDAQ:ALXN) today announced new Phase 2 safety and tolerability
data for CAEL-101, a potentially first-in-class amyloid fibril
targeted therapy, in combination with standard-of-care (SoC)
therapy in patients with AL amyloidosis. The data, presented in two
e-posters at the European Hematology Association (EHA) Congress
2021, strengthen the safety and tolerability profile of CAEL-101,
further support the dose selection for the ongoing Phase 3 study,
and suggest possible cardiac and renal response. An e-poster
featuring the first data from a new arm of the study demonstrated
that CAEL-101 administered in combination with
cyclophosphamide-bortezomib-dexamethasone (CyBorD) plus daratumumab
was generally safe and well-tolerated in the first four weeks of
treatment. Data presented in a second e-poster showed longer-term
evidence that CAEL-101 in combination with CyBorD was generally
well-tolerated for a median treatment duration of 49 weeks, and
exploratory clinical biomarker data suggesting possible cardiac
disease improvements and renal response among patients with cardiac
or renal impairment at baseline, respectively.
This press release features multimedia. View
the full release here:
https://www.businesswire.com/news/home/20210611005037/en/
“AL amyloidosis is a relentless disease that is particularly
devastating when it impacts the heart, with some of these patients
facing a median survival of less than one year following diagnosis.
Current treatments for AL amyloidosis are designed to prevent or
suppress the formation of new amyloids, but they do not address the
existing amyloid buildup in the involved organs like the heart and
kidneys, which can result in continued organ damage and can
ultimately be fatal,” said Michael Spector, President and Chief
Executive Officer of Caelum. “Understanding that CAEL-101 has the
potential to be the first therapy to address the devastating organ
damage caused by AL amyloidosis, we are urgently working to advance
the ongoing CARES Phase 3 program in collaboration with
Alexion.”
Safety and Tolerability of CAEL-101 in Combination with
Cyclophosphamide-Bortezomib-Dexamethasone and Daratumumab in
Patients with AL amyloidosis (#EP1017)
As was previously announced, the Phase 2 study of CAEL‑101 in
combination with CyBorD met its primary objectives, supporting the
safety and tolerability of CAEL-101 and the selection of the 1000
mg/m2 dose for the ongoing Phase 3 study. Results presented from an
additional study arm that included 11 patients receiving CAEL-101
(1000 mg/m2 dose) in combination with CyBorD plus daratumumab
suggested that treatment with this combination was generally
well-tolerated in the first four weeks of treatment. Specifically,
adding daratumumab to the CAEL-101 and CyBorD regimen did not
result in any new safety signals, nor did it alter the
pharmacokinetic (PK) exposure to CAEL-101. The most common adverse
events (AEs) reported in the first four weeks in the additional arm
were nausea, constipation, and insomnia.
Safety and Tolerability of CAEL-101 in Patients with AL
Amyloidosis in a Phase 2 Study for a Median of 49 Weeks
(#EP1018)
Additional longer-term data presented from the Phase 2 study
demonstrated that CAEL-101 in combination with CyBorD in patients
with AL amyloidosis (N=13) was generally well tolerated up to a
median treatment duration of 49 weeks (range 12-57 weeks), with
most patients having received more than 20 infusions of CAEL-101.
The most common AEs reported were diarrhea, nausea, fatigue, rash,
and anemia. In addition, exploratory clinical biomarker evaluations
showed early signals suggesting possible cardiac and renal
response. Specifically, median percent changes for biomarkers of
cardiac disease (cTnT and NT-proBNP) were lower at each subsequent
time point measured, suggesting improvement in cardiac function
among eight patients with active cardiac disease at baseline.
Additionally, seven patients with active renal impairment at
baseline demonstrated renal response, as defined by a decrease of
at least 30 percent in proteinuria (an excess of protein in the
urine) following treatment.
“We are grateful to clinical trial participants who are
essential to advancing our work towards new treatment options for
AL amyloidosis,” said John Orloff, M.D., Executive Vice President
and Head of Research and Development at Alexion. “We remain
committed to working together with the AL amyloidosis community and
Caelum to evaluate the potential of CAEL-101 as a potentially
first-in-class treatment option for patients who are living with
this devastating disease.”
As was previously announced, the Cardiac Amyloid Reaching for
Extended Survival (CARES) Phase 3 clinical program to evaluate
CAEL-101 in combination with SoC therapy in AL amyloidosis has
begun. Enrollment is underway in two parallel Phase 3 studies – one
in patients with Mayo stage IIIa disease (ClinicalTrials.gov
Identifier: NCT04512235) and one in patients with Mayo stage IIIb
disease (ClinicalTrials.gov Identifier: NCT04504825) – and will
collectively enroll approximately 370 patients globally.
About the CAEL-101 Phase 2 Study
The Phase 2 multicenter, open-label, dose-selection study
(ClinicalTrials.gov Identifier: NCT04304144) is designed to
evaluate the safety and tolerability of CAEL-101 in combination
with standard of care (SoC) therapy for patients with AL
amyloidosis and determine the recommended dose for Phase 3 studies.
The study is divided into two parts: Part A examined CAEL-101 in
combination with cyclophosphamide-bortezomib-dexamethasone (CyBorD)
and employed a 3+3 dose escalation design (cohort 1 – 500 mg/m2;
cohort 2 – 750 mg/m2 ; cohort 3 1000 mg/m2); Part A patients were
subsequently up titrated to 1000mg/m2, once this was identified as
the Phase 3 dose. Part B is examining CAEL-101 at the 1000 mg/m2
dose in combination with CyBorD plus daratumumab. Patients from
Parts A and B receive CAEL-101 therapy weekly for the four-week
observation period followed by CAEL-101 doses every other week
thereafter, all while continuing to receive SoC therapy. Patients
continue to receive CAEL-101 per protocol until the end of the
study or discontinuation.
About CAEL-101
CAEL-101 is a first-in-class monoclonal antibody (mAb) designed
to improve organ function by reducing or eliminating amyloid
deposits in the tissues and organs of patients with AL amyloidosis.
The antibody is designed to bind to misfolded light chain proteins
and amyloid and shows binding to both kappa and lambda subtypes. In
a Phase 1a/1b study, CAEL-101 demonstrated improved organ function,
including cardiac and renal function, in 27 patients with relapsed
and refractory AL amyloidosis who had previously not had an organ
response to standard of care therapy. CAEL-101 has received Orphan
Drug Designation from both the U.S. Food and Drug Administration
and European Medicine Agency as a potential therapy for patients
with AL amyloidosis.
About AL Amyloidosis
AL amyloidosis is a rare systemic disorder caused by an
abnormality of plasma cells in the bone marrow. Misfolded
immunoglobulin light chains produced by plasma cells aggregate and
form fibrils that deposit in tissues and organs. This deposition
can cause widespread and progressive organ damage and high
mortality rates, with death most frequently occurring as a result
of cardiac failure. Current standard of care includes plasma cell
directed chemotherapy and autologous stem cell transplant, but
these therapies do not address the organ dysfunction caused by
amyloid deposition, and up to 80 percent of patients are ineligible
for transplant.
AL amyloidosis is a rare disease but is the most common form of
systemic amyloidosis. There are approximately 22,000 patients
across the United States, France, Germany, Italy, Spain and the
United Kingdom. AL amyloidosis has a one-year mortality rate of 47
percent, 76 percent of which is caused by cardiac amyloidosis.
About Caelum Biosciences
Caelum Biosciences, Inc. (“Caelum”) is a clinical-stage
biotechnology company developing treatments for rare and
life-threatening diseases. Caelum’s lead asset, CAEL-101, is a
novel antibody for the treatment of patients with amyloid light
chain (“AL”) amyloidosis. In 2019, Caelum entered a collaboration
agreement with Alexion under which Alexion acquired a minority
equity interest in Caelum and an exclusive option to acquire the
remaining equity in the company. Caelum was founded by Fortress
Biotech, Inc. (NASDAQ: FBIO). For more information, visit
www.caelumbio.com.
About Alexion
Alexion is a global biopharmaceutical company focused on serving
patients and families affected by rare diseases and devastating
conditions through the discovery, development and commercialization
of life-changing medicines. As a leader in rare diseases for more
than 25 years, Alexion has developed and commercializes two
approved complement inhibitors to treat patients with paroxysmal
nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic
syndrome (aHUS), as well as the first and only approved complement
inhibitor to treat anti-acetylcholine receptor (AchR)
antibody-positive generalized myasthenia gravis (gMG) and
neuromyelitis optica spectrum disorder (NMOSD). Alexion also has
two highly innovative enzyme replacement therapies for patients
with life-threatening and ultra-rare metabolic disorders,
hypophosphatasia (HPP) and lysosomal acid lipase deficiency (LAL-D)
as well as the first and only approved Factor Xa inhibitor reversal
agent. In addition, the company is developing several
mid-to-late-stage therapies, including a copper-binding agent for
Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for
rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D
inhibitor as well as several early-stage therapies, including one
for light chain (AL) amyloidosis, a second oral Factor D inhibitor
and a third complement inhibitor. Alexion focuses its research
efforts on novel molecules and targets in the complement cascade
and its development efforts on hematology, nephrology, neurology,
metabolic disorders, cardiology, ophthalmology and acute care.
Headquartered in Boston, Massachusetts, Alexion has offices around
the globe and serves patients in more than 50 countries. This press
release and further information about Alexion can be found at:
www.alexion.com.
[ALXN-P]
Forward-Looking Statement
This press release contains forward-looking statements that
involve risks and uncertainties relating to future events and the
future performance of Alexion (and Caelum) and their products,
including statements related to: CAEL-101 is a potential
first-in-class amyloid fibril targeted therapy; CAEL-101 clinical
studies suggest possible positive cardiac and renal response; the
anticipated or possible benefits of CAEL-101 for patients
(including exploratory clinical biomarker data suggesting possible
cardiac disease improvements and renal response among patients with
cardiac or renal impairment at baseline); CAEL-101 has the
potential to be the first therapy to address the devastating organ
damage caused by AL amyloidosis; exploratory clinical biomarker
evaluations showed early signals suggesting possible cardiac and
renal response; Alexion remains committed to working together with
the AL amyloidosis community and Caelum to evaluate the potential
of CAEL-101 as a potentially first-in-class treatment option for
patients who are living with this devastating disease; CAEL-101 is
designed to improve organ function by reducing or eliminating
amyloid deposits in the tissues and organs of patients with AL
amyloidosis; CAEL-101 is designed to bind to misfolded light chain
protein and amyloid and shows binding to both kappa and lambda
subtypes; and characteristics of clinical trials for CAEL-101
including the number and type of patients expected to be enrolled
in clinical trials. Forward-looking statements are subject to
factors that may cause Alexion's or Caelum’s results and plans to
differ materially from those expected by these forward looking
statements, including for example: CAEL-101 may not generate the
expected benefits to patients that are anticipated (including
safety and efficacy benefits that were reported in earlier clinical
trials); anticipated regulatory approvals may be delayed or
declined; results of clinical trials may not be sufficient to
satisfy regulatory authorities to approve CAEL-101 as a treatment
for AL amyloidosis or other indication (or they may request
additional trials or additional information); results in clinical
trials may not be indicative of results from later stage or larger
clinical trials (or in broader patient populations once the product
is approved for use by regulatory agencies); the possibility that
results of clinical trials are not predictive of safety and
efficacy and potency of CAEL-101 (or failure to adequately operate
or manage clinical trials) which could cause us or Caelum to
discontinue sales of the product (or halt trials, delay or prevent
submission of regulatory approval filings or result in denial of
approval of product candidates); the severity of the impact of the
COVID-19 pandemic on the businesses, including on commercial and
clinical trial and clinical development programs; unexpected delays
in clinical trials; unexpected concerns regarding product
candidates that may arise from additional data or analysis obtained
during clinical trials or obtained once used by patients following
product approval; future product improvements may not be realized
due to expense or feasibility or other factors; delays (expected or
unexpected) in the time it takes regulatory agencies to review and
make determinations on applications for the marketing approval of
products; inability to timely submit (or failure to submit) future
applications for regulatory approval for products and product
candidates; inability to timely initiate (or failure to initiate)
and complete future clinical trials due to safety issues, IRB
decisions, CMC-related issues, expense or unfavorable results from
earlier trials (among other reasons); Alexion dependence on sales
from complement inhibitors; future competition from biosimilars and
novel products; decisions of regulatory authorities regarding the
adequacy of the research, marketing approval or material
limitations on the marketing of products; delays or the inability
to launch product candidates due to regulatory restrictions,
anticipated expense or other matters; interruptions or failures in
the manufacture and supply of products and product candidates;
failure to satisfactorily address matters raised by regulatory
agencies regarding products and product candidates; uncertainty of
long-term success in developing, licensing or acquiring other
product candidates or additional indications for existing products;
the adequacy of pharmacovigilance and drug safety reporting
processes; failure to protect and enforce our data, intellectual
property and proprietary rights and the risks and uncertainties
relating to intellectual property claims, lawsuits and challenges
against us (including intellectual property lawsuits relating to
ULTOMIRIS brought by third parties); the risk that third party
payors (including governmental agencies) will not reimburse or
continue to reimburse for the use of our products at acceptable
rates or at all; failure to realize the benefits and potential of
investments, collaborations, licenses and acquisitions; the
possibility that expected tax benefits will not be realized;
potential declines in sovereign credit ratings or sovereign
defaults in countries where products are sold; delay of collection
or reduction in reimbursement due to adverse economic conditions or
changes in government and private insurer regulations and
approaches to reimbursement; adverse impacts on our supply chain,
clinical trials, manufacturing operations, financial results,
liquidity, hospitals, pharmacies and health care systems from
natural disasters and global pandemics, including the coronavirus;
uncertainties surrounding legal proceedings, company investigations
and government investigations; the risk that estimates regarding
the number of patients with AL amyloidosis and other indications we
are pursuing are inaccurate; the impact of the proposed transaction
between Alexion and AstraZeneca plc; the risks of changing foreign
exchange rates; risks relating to the potential effects of the
Company's restructurings; and a variety of other risks set forth
from time to time in Alexion's filings with the SEC, including but
not limited to the risks discussed in Alexion's Quarterly Report on
Form 10-Q for the quarter ended March 31, 2021 and in our other
filings with the SEC. Alexion and Caelum disclaim any obligation to
update any of these forward-looking statements to reflect events or
circumstances after the date hereof, except when a duty arises
under law.
Forward-Looking Statement Regarding Acquisition of Alexion by
AstraZeneca
This communication contains forward-looking statements within
the meaning of Section 27A of the Securities Act of 1933, as
amended, and Section 21E of the Securities Exchange Act of 1934, as
amended. Forward-looking statements are generally identified by the
use of forward-looking terminology such as “anticipate,” “believe,”
“continue,” “could,” “estimate,” “expect,” “explore,” “evaluate,”
“intend,” “may,” “might,” “plan,” “potential,” “predict,”
“project,” “seek,” “should,” or “will,” or the negative thereof or
other variations thereon or comparable terminology. These
forward-looking statements are only predictions and involve known
and unknown risks and uncertainties, many of which are beyond
Alexion’s and AstraZeneca plc’s “AstraZeneca”) control. Statements
in this communication regarding Alexion, AstraZeneca and the
combined company that are forward-looking, including anticipated
benefits of the proposed transaction, the impact of the proposed
transaction on Alexion’s and AstraZeneca’s businesses and future
financial and operating results, the amount and timing of synergies
from the proposed transaction, the terms and scope of the expected
financing for the proposed transaction, the aggregate amount of
indebtedness of the combined company following the closing of the
proposed transaction, are based on management’s estimates,
assumptions and projections, and are subject to significant
uncertainties and other factors, many of which are beyond Alexion’s
and AstraZeneca’s control. These factors include, among other
things, market factors, competitive product development and
approvals, pricing controls and pressures (including changes in
rules and practices of managed care groups and institutional and
governmental purchasers), economic conditions such as interest rate
and currency exchange rate fluctuations, judicial decisions, claims
and concerns that may arise regarding the safety and efficacy of
in-line products and product candidates, changes to wholesaler
inventory levels, variability in data provided by third parties,
changes in, and interpretation of, governmental regulations and
legislation affecting domestic or foreign operations, including tax
obligations, changes to business or tax planning strategies,
difficulties and delays in product development, manufacturing or
sales including any potential future recalls, patent positions and
the ultimate outcome of any litigation matter. Additional
information concerning these risks, uncertainties and assumptions
can be found in Alexion’s and AstraZeneca’s respective filings with
the SEC, including the risk factors discussed in Alexion’s most
recent Annual Report on Form 10-K, as updated by its Quarterly
Reports on Form 10-Q, in AstraZeneca’s most recent Annual Report on
Form 20-F and in each company’s future filings with the SEC.
Important risk factors could cause actual future results and other
future events to differ materially from those currently estimated
by management, including, but not limited to, the risks that: a
condition to the closing the proposed acquisition may not be
satisfied; a regulatory approval that may be required for the
proposed acquisition is delayed, is not obtained or is obtained
subject to conditions that are not anticipated; AstraZeneca is
unable to achieve the synergies and value creation contemplated by
the proposed acquisition; AstraZeneca is unable to promptly and
effectively integrate Alexion’s businesses; management’s time and
attention is diverted on transaction related issues; disruption
from the transaction makes it more difficult to maintain business,
contractual and operational relationships; the credit ratings of
the combined company declines following the proposed acquisition;
legal proceedings are instituted against Alexion, AstraZeneca or
the combined company; Alexion, AstraZeneca or the combined company
is unable to retain key personnel; and the announcement or the
consummation of the proposed acquisition has a negative effect on
the market price of the capital stock of Alexion or AstraZeneca or
on Alexion’s or AstraZeneca’s operating results. No assurances can
be given that any of the events anticipated by the forward-looking
statements will transpire or occur, or if any of them do occur,
what impact they will have on the results of operations, financial
condition or cash flows of Alexion or AstraZeneca. Should any risks
and uncertainties develop into actual events, these developments
could have a material adverse effect on the proposed transaction
and/or Alexion or AstraZeneca, AstraZeneca’s ability to
successfully complete the proposed transaction and/or realize the
expected benefits from the proposed transaction. You are cautioned
not to rely on Alexion’s and AstraZeneca’s forward-looking
statements. These forward-looking statements are and will be based
upon management’s then-current views and assumptions regarding
future events and operating performance, and are applicable only as
of the dates of such statements. Neither Alexion nor AstraZeneca
assumes any duty to update or revise forward-looking statements,
whether as a result of new information, future events or otherwise,
as of any future date.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20210611005037/en/
Caelum Contacts: Company Michael Spector,
President & Chief Executive Officer mspector@caelumbio.com
Jaclyn Jaffe and Bill Begien Investor Relations (781) 652-4500
info@caelumbio.com
Media Tony Plohoros 6 Degrees (908) 591-2839
tplohoros@6degreespr.com
Alexion Contacts: Media Lisa Taylor, 857-338-9025
Senior Director, Corporate Communications
Investors Chris Stevo, 857-338-9309 Head of Investor
Relations
Alexion Pharmaceuticals (NASDAQ:ALXN)
Gráfico Histórico do Ativo
De Out 2024 até Nov 2024
Alexion Pharmaceuticals (NASDAQ:ALXN)
Gráfico Histórico do Ativo
De Nov 2023 até Nov 2024
