– Data from 75 patients with
transfusion-dependent beta thalassemia or severe sickle cell
disease with follow-up of up to 37.2 months continue to demonstrate
that exa-cel has the potential to be a one-time functional cure
–
– Safety profile generally consistent with
myeloablative conditioning and autologous stem cell transplant
–
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and CRISPR
Therapeutics (Nasdaq: CRSP) announce presentation of new data on
exa-cel, formerly known as CTX001™, from CLIMB-111, CLIMB-121 and
CLIMB-131 highlighting the potentially transformative profile of
this investigational therapy for people with transfusion-dependent
beta thalassemia (TDT) or severe sickle cell disease (SCD) and
provided additional program updates.
New Data for exa-cel from CLIMB Clinical Studies The data
presented at the European Hematology Association (EHA) Congress are
from 75 patients (44 with TDT and 31 with SCD) with follow-up
ranging from 1.2 to 37.2 months after exa-cel dosing.
Of the 44 patients with TDT, 26 had beta-zero/beta-zero or other
beta-zero-like severe genotypes. Forty-two of 44 patients with TDT
were transfusion-free with follow-up ranging from 1.2 to 37.2
months after exa-cel infusion. Two patients who were not yet
transfusion-free had 75% and 89% reductions in transfusion volume.
TDT patients had substantial mean increases in fetal hemoglobin
(HbF) and corresponding increases in mean total hemoglobin (Hb)
with mean total Hb levels increasing to >11 g/dL by Month 3 and
maintained thereafter.
All 31 patients with severe SCD characterized by recurrent
vaso-occlusive crises (VOCs) (mean of 3.9 VOCs per year over the
prior two years) were free of VOCs after exa-cel infusion through
duration of follow-up, with follow-up ranging from 2.0 to 32.3
months. SCD patients had mean HbF (as a proportion of total Hb) of
approximately 40% by Month 4 and maintained thereafter.
The safety was generally consistent with myeloablative
conditioning with busulfan and autologous stem cell transplant. All
patients engrafted neutrophils and platelets after exa-cel
infusion. Among the 44 patients with TDT, two patients had serious
adverse events (SAEs) considered related to exa-cel. As previously
reported, one patient had three SAEs considered related to exa-cel,
hemophagocytic lymphohistiocytosis (HLH), acute respiratory
distress syndrome and headache, and one SAE of idiopathic pneumonia
syndrome that was considered related to both exa-cel and busulfan.
All four SAEs occurred in the context of HLH and have resolved. One
patient had SAEs of delayed neutrophil engraftment and
thrombocytopenia, both of which were considered related to exa-cel
and busulfan, and both SAEs have resolved. Among the 31 patients
with SCD, there were no SAEs considered related to exa-cel.
Additional details were presented during the EHA media briefing
and can be found in the published abstract and presentation.
Late-breaking abstract #LB2367 entitled “Efficacy and Safety of
a Single Dose of CTX001 For Transfusion-Dependent Βeta-Thalassemia
and Severe Sickle Cell Disease,” will be an oral presentation on
Sunday, June 12 at 09:45-11:15 CEST.
“These robust data from 75 patients, of which 33 have one year
or more of follow-up after exa-cel infusion, further demonstrate
the potential of this investigational therapy as a one-time
functional cure for patients with transfusion-dependent beta
thalassemia or severe sickle cell disease,” said Carmen Bozic,
M.D., Executive Vice President, Global Medicines Development and
Medical Affairs, and Chief Medical Officer at Vertex.
“By reactivating a naturally occurring developmental process,
exa-cel restores fetal hemoglobin production and thereby can
ameliorate the course of these diseases,” said Haydar Frangoul,
M.D., Medical Director of Pediatric Hematology and Oncology at
Sarah Cannon Research Institute, HCA Healthcare’s The Children’s
Hospital at TriStar Centennial Medical Center. “The remarkable
results based on this approach give me great optimism and
confidence in the potential of this treatment for patients.”
“I have seen first-hand the impact that this investigational
therapy has had on patients in these clinical trials and continue
to be impressed by the totality of the data,” said Franco
Locatelli, M.D., Ph.D., Professor of Pediatrics at the Sapienza
University of Rome, Director of the Department of Pediatric
Hematology and Oncology at Bambino Gesù Children’s Hospital. “Given
the urgency for highly effective and curative therapies for
patients with hemoglobinopathies, I am excited to be part of the
team working towards the goal of addressing this unmet need.”
Exa-cel Study Updates Following ongoing discussions with
regulators, the clinical trial protocols for CLIMB-111 and
CLIMB-121 were amended to incorporate feedback on the primary
endpoints for regulatory submission. Specifically, the primary
endpoint in CLIMB-111 for TDT has been amended from proportion of
subjects achieving transfusion reduction after exa-cel infusion to
proportion of subjects maintaining weighted average Hb ≥9 g/dL
without red blood cell (RBC) transfusions for at least 12
consecutive months after exa-cel infusion.
The primary endpoint in CLIMB-121 for SCD has been updated from
proportion of subjects with HbF ≥20% after exa-cel infusion, to
proportion of subjects who have not experienced any severe VOCs for
at least 12 consecutive months after exa-cel infusion.
Both clinical trials are now in Phase 3 and are fully enrolled.
All patients will have the opportunity to join CLIMB-131, a
long-term follow-up study, after completing participation in the
initial studies.
Additional Pediatric Studies In line with the company’s
strategy of developing therapies for patients of all ages, two
additional Phase 3 studies of exa-cel have begun. Earlier this
year, the Independent Data Monitoring Committee (DMC) met to review
the data in adults and adolescents and endorsed expanding into
younger pediatric patients. CLIMB-141 and CLIMB-151 are Phase 3
open-label trials designed to assess the safety and efficacy of a
single dose of exa-cel in patients ages 2 to 11 years with TDT or
SCD, respectively. The trials are now open for enrollment and
currently enrolling patients ages 5 to 11 years and will plan to
extend to patients 2 to less than 5 years of age at a later date.
Each trial will enroll approximately 12 patients. Patients will be
followed for approximately two years after infusion. Each patient
will be asked to participate in CLIMB-131, a long-term follow-up
trial.
Vertex also presented three additional abstracts on the
burden of disease in sickle cell disease and beta thalassemia at
the EHA Congress.
- Abstract #P1704 entitled “Projected Lifetime Economic Burden of
Severe Sickle Cell Disease in the United States,” presented via
poster on Friday, June 10 at 16:30-17:45 CEST.
- Abstract #P1703 entitled “Economic Burden of
Transfusion-Dependent Beta-Thalassemia in the United States,”
presented via poster on Friday, June 10 at 16:30-17:45 CEST.
- Abstract #P1482 entitled “Patients With Severe Sickle Cell
Disease on Standard-of-Care Treatment Are Very Unlikely to Become
VOC-Free for One Year: A Cohort Study of Medicaid Enrollees,”
presented via poster on Friday, June 10 at 16:30-17:45 CEST.
About exagamglogene autotemcel (exa-cel) Exa‑cel,
formerly known as CTX001, is an investigational, autologous, ex
vivo CRISPR/Cas9 gene‑edited therapy that is being evaluated for
patients with TDT or SCD characterized by recurrent VOCs, in which
a patient’s own hematopoietic stem cells are edited to produce high
levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells.
HbF is the form of the oxygen‑carrying hemoglobin that is naturally
present during fetal development, which then switches to the adult
form of hemoglobin after birth. The elevation of HbF by exa‑cel has
the potential to alleviate transfusion requirements for patients
with TDT and reduce painful and debilitating sickle crises for
patients with SCD. Earlier results from these ongoing trials were
published in The New England Journal of Medicine in January of
2021.
Based on progress in this program to date, exa‑cel has been
granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track,
Orphan Drug, and Rare Pediatric Disease designations from the U.S.
Food and Drug Administration (FDA) for both TDT and SCD. Exa-cel
has also been granted Orphan Drug Designation from the European
Commission, as well as Priority Medicines (PRIME) designation from
the European Medicines Agency (EMA), for both TDT and SCD.
Among gene‑editing approaches being evaluated for TDT and SCD,
exa‑cel is the furthest advanced in clinical development.
About CLIMB‑111 and CLIMB‑121 The ongoing Phase 1/2/3
open‑label trials, CLIMB‑111 and CLIMB‑121, are designed to assess
the safety and efficacy of a single dose of exa‑cel in patients
ages 12 to 35 years with TDT or with SCD, characterized by
recurrent VOCs, respectively. The trials are now closed for
enrollment. Patients will be followed for approximately two years
after exa‑cel infusion. Each patient will be asked to participate
in CLIMB‑131, a long‑term follow‑up trial.
About CLIMB-131 This is a long‑term, open‑label trial to
evaluate the safety and efficacy of exa‑cel in patients who
received exa‑cel in CLIMB‑111, CLIMB‑121, CLIMB‑141 or CLIMB‑151.
The trial is designed to follow participants for up to 15 years
after exa‑cel infusion.
About CLIMB‑141 and CLIMB‑151 The ongoing Phase 3
open-label trials, CLIMB‑141 and CLIMB‑151, are designed to assess
the safety and efficacy of a single dose of exa‑cel in patients
ages 2 to 11 years with TDT or with SCD, characterized by recurrent
VOCs, respectively. The trials are now open for enrollment and
currently enrolling patients ages 5 to 11 years of age and will
plan to extend to patients 2 to less than 5 years of age at a later
date. Each trial will enroll approximately 12 patients. Patients
will be followed for approximately two years after infusion. Each
patient will be asked to participate in CLIMB-131, a long‑term
follow‑up trial.
About the Gene‑Editing Process in These Trials Patients
who enroll in these trials will have their own hematopoietic stem
and progenitor cells collected from peripheral blood. The patient’s
cells will be edited using the CRISPR/Cas9 technology. The edited
cells, exa‑cel, will then be infused back into the patient as part
of an autologous hematopoietic stem cell transplant (HSCT), a
process which involves a patient being treated with myeloablative
busulfan conditioning. Patients undergoing HSCT may also encounter
side effects (ranging from mild to severe) that are unrelated to
the administration of exa‑cel. Patients will initially be monitored
to determine when the edited cells begin to produce mature blood
cells, a process known as engraftment. After engraftment, patients
will continue to be monitored to track the impact of exa‑cel on
multiple measures of disease and for safety.
About the Vertex‑CRISPR Collaboration Vertex and CRISPR
Therapeutics entered into a strategic research collaboration in
2015 focused on the use of CRISPR/Cas9 to discover and develop
potential new treatments aimed at the underlying genetic causes of
human disease. Exa‑cel represents the first potential treatment to
emerge from the joint research program. Under an amended
collaboration agreement, Vertex now leads global development,
manufacturing and commercialization of exa‑cel and splits program
costs and profits worldwide 60/40 with CRISPR Therapeutics.
About Vertex Vertex is a global biotechnology company
that invests in scientific innovation to create transformative
medicines for people with serious diseases. The company has
multiple approved medicines that treat the underlying cause of
cystic fibrosis (CF) — a rare, life-threatening genetic disease —
and has several ongoing clinical and research programs in CF.
Beyond CF, Vertex has a robust pipeline of investigational small
molecule, cell and genetic therapies in other serious diseases
where it has deep insight into causal human biology, including
sickle cell disease, beta thalassemia, APOL1‑mediated kidney
disease, pain, type 1 diabetes, alpha‑1 antitrypsin deficiency and
Duchenne muscular dystrophy.
Founded in 1989 in Cambridge, Mass., Vertex's global
headquarters is now located in Boston's Innovation District and its
international headquarters is in London. Additionally, the company
has research and development sites and commercial offices in North
America, Europe, Australia and Latin America. Vertex is
consistently recognized as one of the industry's top places to
work, including 12 consecutive years on Science magazine's Top
Employers list and one of the 2021 Seramount (formerly Working
Mother Media) 100 Best Companies. For company updates and to learn
more about Vertex's history of innovation, visit www.vrtx.com or
follow us on Facebook, Twitter, LinkedIn, YouTube and
Instagram.
(VRTX-GEN)
Vertex Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as defined
in the Private Securities Litigation Reform Act of 1995, as
amended, including, without limitation, (i) statements by Dr.
Carmen Bozic, Dr. Haydar Frangoul, and Dr. Franco Locatelli in this
press release, (ii) our plans and expectations to present clinical
data from the ongoing exa-cel clinical trials during the EHA
Congress, (iii) the progress of the ongoing exa-cel clinical
trials, including expectations regarding the abstracts that will be
made available on the virtual platform including anticipated
projections and estimates related to the various economic impacts
of SCD and TDT, (iv) the potential benefits, efficacy, and safety
of exa-cel, including the potentially transformative nature of the
therapy and the potential of the treatment for patients, (v) our
plans and expectations for our clinical trials and pipeline
products, and (vi) the status of our clinical trials of our product
candidates under development by us and our collaborators, including
activities at the clinical trial sites, patient enrollment, and
expectations regarding clinical trial follow-up. While Vertex
believes the forward-looking statements contained in this press
release are accurate, these forward-looking statements represent
the company's beliefs only as of the date of this press release and
there are a number of risks and uncertainties that could cause
actual events or results to differ materially from those expressed
or implied by such forward-looking statements. Those risks and
uncertainties include, among other things, that data from a limited
number of patients may not be indicative of final clinical trial
results, that data from the company's development programs,
including its programs with its collaborators, may not support
registration or further development of its compounds due to safety
and/or efficacy, or other reasons, that internal or external
factors could delay, divert, or change our plans and objectives
with respect to our research and development programs, that future
competitive or other market factors may adversely affect the
commercial potential for exa-cel, and other risks listed under the
heading “Risk Factors” in Vertex's most recent annual report and
subsequent quarterly reports filed with the Securities and Exchange
Commission (SEC) and available through the company's website at
www.vrtx.com and on the SEC’s website at www.sec.gov. You should
not place undue reliance on these statements or the scientific data
presented. Vertex disclaims any obligation to update the
information contained in this press release as new information
becomes available.
(CRSP-GEN)
About CRISPR Therapeutics CRISPR Therapeutics is a
leading gene editing company focused on developing transformative
gene-based medicines for serious diseases using its proprietary
CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing
technology that allows for precise, directed changes to genomic
DNA. CRISPR Therapeutics has established a portfolio of therapeutic
programs across a broad range of disease areas including
hemoglobinopathies, oncology, regenerative medicine and rare
diseases. To accelerate and expand its efforts, CRISPR Therapeutics
has established strategic collaborations with leading companies
including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR
Therapeutics AG is headquartered in Zug, Switzerland, with its
wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and
R&D operations based in Cambridge, Massachusetts, and business
offices in San Francisco, California and London, United Kingdom.
For more information, please visit www.crisprtx.com.
CRISPR THERAPEUTICS® word mark and design logo and CTX001™ are
trademarks and registered trademarks of CRISPR Therapeutics AG. All
other trademarks and registered trademarks are the property of
their respective owners.
CRISPR Therapeutics Forward-Looking Statement This press
release may contain a number of “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, as well as statements made by Dr. Carmen Bozic,
Dr. Haydar Frangoul, and Dr. Franco Locatelli in this press
release, as well as statements regarding CRISPR Therapeutics’
expectations about any or all of the following: i) the safety,
efficacy and clinical progress of the ongoing exa-cel clinical
trials, including expectations regarding the abstracts that will be
made available on the virtual platform and our plans and
expectations to present and the clinical data that are being
presented during the EHA Congress, as well as the potentially
transformative nature of exa-cel and the potential of the treatment
for patients; and (ii) the therapeutic value, development, and
commercial potential of CRISPR/Cas9 gene editing technologies and
therapies. Without limiting the foregoing, the words “believes,”
“anticipates,” “plans,” “expects” and similar expressions are
intended to identify forward-looking statements. You are cautioned
that forward-looking statements are inherently uncertain. Although
CRISPR Therapeutics believes that such statements are based on
reasonable assumptions within the bounds of its knowledge of its
business and operations, existing and prospective investors are
cautioned that forward-looking statements are inherently uncertain,
are neither promises nor guarantees and not to place undue reliance
on such statements, which speak only as of the date they are made.
Actual performance and results may differ materially from those
projected or suggested in the forward-looking statements due to
various risks and uncertainties. These risks and uncertainties
include, among others: the potential for initial and preliminary
data from any clinical trial and initial data from a limited number
of patients (as is the case with exa-cel at this time) not to be
indicative of final or future trial results; the potential that the
exa-cel clinical trial results may not be favorable or may not
support registration or further development; that future
competitive or other market factors may adversely affect the
commercial potential for exa-cel; CRISPR Therapeutics may not
realize the potential benefits of its collaboration with Vertex;
potential impacts due to the coronavirus pandemic, such as to the
timing and progress of clinical trials; uncertainties regarding the
intellectual property protection for CRISPR Therapeutics’
technology and intellectual property belonging to third parties;
and those risks and uncertainties described under the heading “Risk
Factors” in CRISPR Therapeutics’ most recent annual report on Form
10-K, quarterly report on Form 10-Q, and in any other subsequent
filings made by CRISPR Therapeutics with the U.S. Securities and
Exchange Commission, which are available on the SEC's website at
www.sec.gov. CRISPR Therapeutics disclaims any obligation or
undertaking to update or revise any forward-looking statements
contained in this press release, other than to the extent required
by law.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20220611005003/en/
Vertex Pharmaceuticals Incorporated Investors:
Michael Partridge, +1 617-341-6108 Or Manisha Pai, +1 617-961-1899
Or Miroslava Minkova, +1 617-341-6135
Media: mediainfo@vrtx.com or U.S.: +1 617-341-6992 or
Heather Nichols: +1 617-839-3607 or International: +44 20 3204
5275
CRISPR Therapeutics Investors: Susan Kim, +1
617-307-7503 susan.kim@crisprtx.com
Media: Rachel Eides, +1-617-315-4493.
rachel.eides@crisprtx.com
Vertex Pharmaceuticals (NASDAQ:VRTX)
Historical Stock Chart
From Apr 2024 to May 2024
Vertex Pharmaceuticals (NASDAQ:VRTX)
Historical Stock Chart
From May 2023 to May 2024