- Phase 2 study met primary endpoint and all
secondary endpoints -
- Phase 2 data demonstrated that a once-daily
triple combination of VX-121/ tezacaftor/VX-561 has potential for
enhanced clinical benefit compared to TRIKAFTA®
(elexacaftor/tezacaftor/ivacaftor and ivacaftor) -
- Initiation of Phase 3 program expected in the
second half of 2021 -
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced the company will initiate a Phase 3 development program
for the new once-daily investigational triple combination of
VX-121/tezacaftor/VX-561 (deutivacaftor) in the second half of
2021. The combination of VX-121/tezacaftor/VX-561 was first
identified as having potential for increased efficacy based on its
ability to drive higher levels of chloride transport compared to
TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) in human
bronchial epithelial cells in vitro. The combination of
VX-121/tezacaftor/VX-561 was evaluated in a Phase 2 study in people
with cystic fibrosis (CF) ages 18 and older with one F508del
mutation and one minimal function mutation (F/MF) and in people
with CF ages 18 and older with two F508del mutations (F/F). The
regimen was generally well-tolerated, and the study met the primary
efficacy endpoint of absolute change from baseline in ppFEV1 and
all secondary efficacy endpoints including absolute change from
baseline in sweat chloride concentration in both patient
populations. Taken together, these data suggest the triple
combination holds the potential to restore cystic fibrosis
transmembrane conductance regulator (CFTR) function in people with
CF to even higher levels than seen with other Vertex CFTR
modulators and thereby provide enhanced clinical benefit.
“TRIKAFTA has demonstrated high levels of efficacy in people
with CF who have at least one F508del mutation. However, we remain
committed to continuing our efforts to maximize the benefit and
convenience we can deliver for these patients,” said Carmen Bozic,
M.D., Executive Vice President, Global Medicines Development and
Medical Affairs, and Chief Medical Officer at Vertex. “With this
once-daily, next-in-class, triple combination regimen, our goal is
to develop a more effective treatment regimen with the potential to
restore CFTR function in people with CF to even higher levels than
currently achievable.”
Phase 2 Study Results:
Results from Phase 2 study of
VX-121/ tezacaftor/VX-561 in adults with one F508del and one
minimal function mutation (F/MF). Results shown are mean absolute
within-group change from baseline through Day 29*
ppFEV1
(Percentage
Points)
Sweat Chloride
(mmol/L)
F/MF Treatment Group
Placebo n=10
+1.9
(p=0.5214)
+2.3
(p=0.6198)
VX-121 (5 mg qd)/tezacaftor (100
mg qd)/VX-561 (150 mg qd) Triple Combination Regimen n=9
+4.6
(p=0.1253)
-42.8
(p<0.0001)
VX-121 (10 mg qd)/ tezacaftor
(100 mg qd)/VX-561 (150 mg qd) Triple Combination Regimen n=19
+14.2
(p<0.0001)
-45.8
(p<0.0001)
VX-121 (20 mg qd)/ tezacaftor
(100 mg qd)/ VX-561 (150 mg qd) Triple Combination Regimen n=20
+9.8
(p<0.0001)
-49.5
(p<0.0001)
Results from Phase 2 study of
VX-121/ tezacaftor/VX-561 in adults with two F508del mutations
(F/F). Results shown are mean absolute within-group change from
baseline (after 4-week run-in on tezacaftor/ivacaftor) through Day
29*
ppFEV1
(Percentage
Points)
Sweat Chloride
(mmol/L)
F/F Treatment Group
Tezacaftor (100 mg qd)/ivacaftor
(150 mg q12h) (active control) n=10
-0.1
(p=0.9635)
-2.6
(p=0.3633)
VX-121 (20 mg qd)/ tezacaftor
(100 mg qd)/VX-561 (150 mg qd) Triple Combination Regimen n=18
+15.9
(p<0.0001)
-45.5
(p<0.0001)
*The primary efficacy analysis is the mean
absolute within-group change from baseline in ppFEV1 through Day 29
for any VX-121/tezacaftor/VX-561 dose group.
VX-561 was also evaluated in a dose-ranging monotherapy study.
Complete data from the Phase 2 clinical study of
VX-121/tezacaftor/VX-561 and the VX-561 Phase 2 monotherapy study
will be presented at a later date.
About the Phase 3 Program
The Phase 3 program consists of two randomized, double-blind,
active-controlled 48-week trials, which will evaluate the safety
and efficacy of VX-121 (20 mg)/tezacaftor (100 mg)/VX-561 (250 mg)
in comparison to TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and
ivacaftor). The first study will enroll approximately 350 people
with CF ages 12 years and older with one F508del mutation and one
minimal function mutation (F/MF). The second study will enroll
approximately 450 people with CF ages 12 years and older with two
F508del mutations (F/F) or one F508del mutation and a second
mutation responsive to CFTR modulators. The primary endpoint in
both studies is the absolute change from baseline in ppFEV1, which
will be analyzed for non-inferiority to TRIKAFTA. Both studies will
also assess absolute change from baseline in ppFEV1 and sweat
chloride for superiority to TRIKAFTA®.
About VX-121/Tezacaftor/VX-561
In people with certain types of mutations in the CFTR gene, the
CFTR protein is not processed and cannot move through the cell
normally. This results in little to no protein at the cell surface.
VX-121 and tezacaftor are designed to increase the amount of mature
protein at the cell surface by targeting the processing and
trafficking defect of the CFTR protein. VX-561 (deutivacaftor) is
an investigational potentiator designed to keep CFTR proteins at
the cell surface open longer to improve the flow of salt and water
across the cell membrane, which helps hydrate and clear mucus from
the airways. The VX-121/tezacaftor/VX-561 program was granted Fast
Track and Orphan Drug Designations from the U.S. Food and Drug
Administration for the treatment of cystic fibrosis.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR TRIKAFTA®
(elexacaftor/tezacaftor/ivacaftor and ivacaftor) TABLETS
What is TRIKAFTA?
TRIKAFTA is a prescription medicine used for the treatment of
cystic fibrosis (CF) in patients aged 6 years and older who have at
least one copy of the F508del mutation in the cystic fibrosis
transmembrane conductance regulator (CFTR) gene or another mutation
that is responsive to treatment with TRIKAFTA. Patients should talk
to their doctor to learn if they have an indicated CF gene
mutation. It is not known if TRIKAFTA is safe and effective in
children under 6 years of age.
Patients should not take TRIKAFTA if they take certain
medicines or herbal supplements, such as: antibiotics such as
rifampin or rifabutin; seizure medicines such as phenobarbital,
carbamazepine, or phenytoin; or St. John’s wort.
Before taking TRIKAFTA, patients should tell their doctor
about all of their medical conditions, including if they: have
kidney problems; have or have had liver problems; are pregnant or
plan to become pregnant because it is not known if TRIKAFTA will
harm an unborn baby; or are breastfeeding or planning to breastfeed
because it is not known if TRIKAFTA passes into breast milk.
TRIKAFTA may affect the way other medicines work, and other
medicines may affect how TRIKAFTA works. Therefore, the dose of
TRIKAFTA may need to be adjusted when taken with certain medicines.
Patients should especially tell their doctor if they take:
antifungal medicines including ketoconazole, itraconazole,
posaconazole, voriconazole, or fluconazole; antibiotics including
telithromycin, clarithromycin, or erythromycin.
TRIKAFTA may cause dizziness in some people who take it.
Patients should not drive a car, operate machinery, or do anything
that requires alertness until they know how TRIKAFTA affects
them.
Patients should avoid food or drink that contains
grapefruit while they are taking TRIKAFTA.
TRIKAFTA can cause serious side effects, including:
High liver enzymes in the blood, which is a common side
effect in people treated with TRIKAFTA. These can be serious and
may be a sign of liver injury. The patient's doctor will do blood
tests to check their liver before they start TRIKAFTA, every 3
months during the first year of taking TRIKAFTA, and every year
while taking TRIKAFTA. Patients should call their doctor right away
if they have any of the following symptoms of liver problems: pain
or discomfort in the upper right stomach (abdominal) area;
yellowing of the skin or the white part of the eyes; loss of
appetite; nausea or vomiting; dark, amber-colored urine.
Abnormality of the eye lens (cataract) has happened in
some children and adolescents treated with TRIKAFTA. If the patient
is a child or adolescent, their doctor should perform eye
examinations before and during treatment with TRIKAFTA to look for
cataracts.
The most common side effects of TRIKAFTA include
headache, upper respiratory tract infection (common cold) including
stuffy and runny nose, stomach (abdominal) pain, diarrhea, rash,
increase in liver enzymes, increase in a certain blood enzyme
called creatine phosphokinase, flu (influenza), inflamed sinuses,
and increase in blood bilirubin.
These are not all the possible side effects of TRIKAFTA.
Please click the product link to see the full Prescribing
Information for TRIKAFTA.
About Cystic Fibrosis
Cystic Fibrosis (CF) is a rare, life-shortening genetic disease
affecting more than 80,000 people globally. CF is a progressive,
multi-system disease that affects the lungs, liver, GI tract,
sinuses, sweat glands, pancreas and reproductive tract. CF is
caused by a defective and/or missing CFTR protein resulting from
certain mutations in the CFTR gene. Children must inherit two
defective CFTR genes — one from each parent — to have CF. While
there are many different types of CFTR mutations that can cause the
disease, the vast majority of all people with CF have at least one
F508del mutation. These mutations, which can be determined by a
genetic test, or genotyping test, lead to CF by creating
non-working and/or too few CFTR proteins at the cell surface. The
defective function and/or absence of CFTR protein results in poor
flow of salt and water into and out of the cells in a number of
organs. In the lungs, this leads to the buildup of abnormally
thick, sticky mucus that can cause chronic lung infections and
progressive lung damage in many patients that eventually leads to
death. The median age of death is in the early 30s.
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 medicines in other
serious diseases where it has deep insight into causal human
biology, including pain, alpha-1 antitrypsin deficiency and
APOL1-mediated kidney diseases. In addition, Vertex has a rapidly
expanding pipeline of cell and genetic therapies for diseases such
as sickle cell disease, beta thalassemia, Duchenne muscular
dystrophy and type 1 diabetes mellitus.
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 11 consecutive years on Science magazine's Top
Employers list and a best place to work for LGBTQ equality by the
Human Rights Campaign. 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.
Special Note Regarding Forward-Looking Statements
This press release contains forward-looking statements as
defined in the Private Securities Litigation Reform Act of 1995,
including, without limitation, statements made by Dr. Carmen Bozic
in this press release and statements regarding our expectations and
plans for the Phase 3 development program for the new once-daily
triple combination of VX-121/tezacaftor/VX-561, including the
timing of program initiation and patient enrollment, our
expectations for the benefits and potential of the new triple
combination, including our beliefs for the enhanced clinical
benefit compared to TRIKAFTA®, and our expectations that data from
the Phase 2 studies will be presented at a later date. 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 the Phase 3 development program evaluating the new
triple combination may not be initiated or completed on the
anticipated timeline, or at all, that data from the company's
development programs may not support registration or further
development of its compounds due to safety, efficacy, or other
reasons, and other risks listed under the heading “Risk Factors” in
Vertex's most recent annual report and subsequent filings filed
with the Securities and Exchange Commission at www.sec.gov and
available through the company's website at www.vrtx.com. 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.
(VRTX-GEN)
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Vertex Pharmaceuticals Incorporated Investors:
Michael Partridge, +1 617-341-6108 or Brenda Eustace, +1
617-341-6187 or Manisha Pai, +1 617-429-6891
Media: mediainfo@vrtx.com or U.S.: +1 617-341-6992 or
Heather Nichols: +1 617-839-3607 or International: +44 20 3204
5275
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