Accueil / Communiqués / Two Phase 3 Studies of the Triple Combination of VX-445, Tezacaftor and Ivacaftor Met Primary Endpoint of Improvement in Lung Function (ppFEV1) in People with Cystic Fibrosis

Two Phase 3 Studies of the Triple Combination of VX-445, Tezacaftor and Ivacaftor Met Primary Endpoint of Improvement in Lung Function (ppFEV1) in People with Cystic Fibrosis

Wednesday, March 6th 2019 at 1:00pm UTC

-Mean absolute improvement in ppFEV1 of 13.8
percentage points from baseline at week 4 in people with one F508del
mutation and one minimal function mutation (F/MF) compared to placebo
(p<0.0001)-

-Mean absolute improvement in ppFEV1 of 10.0
percentage points from baseline at week 4 when VX-445 was added in
people with two F508del mutations (F/F) already receiving tezacaftor and
ivacaftor compared to control group of placebo added to tezacaftor and
ivacaftor (p<0.0001)-

-Safety and efficacy profile reported today supports potential
submission of a New Drug Application for the VX-445 triple combination
regimen-

-Vertex plans to seek global regulatory approvals for either VX-659
or VX-445 triple combination regimen in both F/F and F/MF patient
populations concurrently based on final 24-week data for both regimens
expected in the second quarter of 2019-

-U.S. NDA and EU MAA planned for the third and fourth quarters of
2019, respectively-

BOSTON–(BUSINESS WIRE)– Vertex
Pharmaceuticals Incorporated
(Nasdaq: VRTX) today announced that
treatment with the triple combination of the next-generation corrector
VX-445, tezacaftor and ivacaftor resulted in statistically significant
improvements in lung function (percent predicted forced expiratory
volume in one second, or ppFEV1) in two Phase 3 studies in
people with cystic fibrosis (CF). Data from a pre-specified interim
analysis of the Phase 3 study in people with one F508del mutation
and one minimal function mutation showed a mean absolute improvement in
ppFEV1 of 13.8 percentage points from baseline at week 4 of
treatment compared to placebo (p<0.0001). In the Phase 3 study in people
with two F508del mutations, the addition of VX-445 in patients
already receiving tezacaftor and ivacaftor resulted in a mean absolute
improvement in ppFEV1 of 10.0 percentage points from baseline
at week 4 of treatment compared to the control group in whom placebo was
added to tezacaftor and ivacaftor (p<0.0001). The VX-445 triple
combination regimen was generally well tolerated, and the safety and
efficacy profile from the results released today supports the potential
submission of a New Drug Application (NDA) for the VX-445 triple
combination regimen.

The Phase 3 data announced today for the VX-445 triple combination
regimen follow Phase 3 data announced in late 2018 for the triple
combination of VX-659, tezacaftor and ivacaftor that also showed a
safety and efficacy profile supportive of a potential NDA submission.
Given the similarity of the data for the 4-week primary efficacy
endpoint for the VX-659 and VX-445 regimens and the near-term
availability of the final 24-week data for both regimens in the second
quarter of 2019, Vertex plans to utilize these final 24-week data to
choose the best regimen to submit for regulatory approvals globally.
Because these submissions will include the final 24-week data, Vertex
will seek approval for patients ages 12 and older with one F508del
mutation and one minimal function mutation and for patients with two F508del
mutations concurrently. Vertex plans to submit an NDA to the U.S. FDA in
the third quarter of 2019 and a Marketing Authorization Application
(MAA) in Europe in the fourth quarter of 2019 for either the VX-659 or
VX-445 triple combination regimen. The company also plans to disclose
more detailed data from the Phase 3 studies of the selected triple
combination regimen, including 24-week data from the study in patients
with one F508del mutation and one minimal function mutation, in
the second quarter of 2019.

“Both the VX-659 and VX-445 triple combination regimens showed highly
consistent and significant improvements in lung function across our
Phase 3 programs, underscoring the important clinical benefit that a
triple combination regimen may provide to patients with two F508del
mutations and to those with one F508del and one minimal function
mutation,” said Reshma Kewalramani, M.D., Executive Vice President,
Global Medicines Development and Medical Affairs and Chief Medical
Officer at Vertex. “We look forward to submitting global regulatory
applications for one of these triple combination regimens for both
patient populations later this year.”

About the VX-445 Phase 3 Study in People with One F508del
Mutation and One Minimal Function Mutation

The data announced today for people ages 12 and older with one F508del
mutation and one minimal function mutation are from an ongoing,
randomized, double-blind, placebo-controlled Phase 3 study evaluating
the triple combination of VX-445, tezacaftor and ivacaftor compared to
triple placebo for 24 weeks. The study randomized 405 patients, and 403
patients received at least one dose of either the VX-445 triple
combination regimen or triple placebo. In the U.S., the primary endpoint
of the study is the mean absolute change in ppFEV1 from
baseline at week 4 of triple combination treatment compared to triple
placebo. The data announced today are from a pre-specified interim
analysis that evaluated the primary endpoint at week 4. 402 patients had
completed the week 4 visit of the study at the time of the interim
analysis. The safety and efficacy profile in the interim analysis
supports the potential submission of an NDA for the VX-445 triple
combination regimen for patients with one F508del mutation and
one minimal function mutation.

Topline Data:

Treatment with the triple combination of VX-445, tezacaftor and
ivacaftor resulted in a mean absolute improvement in ppFEV1 of
13.8 percentage points from baseline at week 4 compared to triple
placebo (p<0.0001), which was the primary endpoint of the study. The
mean absolute within-group improvement in ppFEV1 for those
who received the VX-445 triple combination regimen was 13.6 percentage
points from baseline at week 4. The mean absolute within-group change in
ppFEV1 for those who received triple placebo was -0.2
percentage points from baseline at week 4.

The VX-445 triple combination regimen was generally well tolerated in
this study. The safety profile reflects all available safety data for
all patients at the time of the interim analysis, including 246 patients
who had reached the week 12 visit (123 patients who were randomized to
the VX-445 triple combination regimen and 123 patients randomized to
triple placebo) and 65 patients who had completed the 24-week treatment
period (29 patients randomized to receive the VX-445 triple combination
regimen and 36 patients randomized to receive triple placebo).

This study is ongoing to evaluate the VX-445 triple combination regimen
for a total of 24 weeks and will generate additional safety and efficacy
data and data for key secondary endpoints, including the number of
pulmonary exacerbations, change in sweat chloride, change in
patient-reported outcomes as measured by the respiratory domain score of
the Cystic Fibrosis Questionnaire-Revised (CFQ-R) and change in body
mass index, among others.

Open-Label Extension Study:

All patients who complete treatment in the 24-week study, regardless of
treatment assignment, are given the opportunity to enroll in a rollover
study where all patients receive the VX-445 triple combination regimen.
All patients who had completed the study at the time of the interim
analysis elected to enter the open-label extension study.

About the VX-445 Phase 3 Study in People with Two F508del
Mutations

The data announced today for people with two F508del mutations
are from a randomized, double-blind, controlled Phase 3 study that
evaluated four weeks of treatment with the triple combination of VX-445,
tezacaftor, and ivacaftor compared to placebo, tezacaftor and ivacaftor.
The study randomized 108 patients ages 12 years or older who have two
F508del mutations. All patients received tezacaftor in combination with
ivacaftor during a 4-week run-in prior to randomization, and 107 of the
108 patients who were randomized received at least 1 dose of either the
triple combination of VX-659, tezacaftor and ivacaftor or placebo,
tezacaftor and ivacaftor. The primary endpoint of the study was the mean
absolute change in ppFEV1 from baseline (end of the 4-week
tezacaftor/ivacaftor run-in) at week 4 of triple combination of VX-445,
tezacaftor and ivacaftor compared to placebo in combination with
tezacaftor and ivacaftor. The data announced today reflect topline data
from the primary efficacy and safety analysis conducted once all (n=107)
patients completed the study. The safety and efficacy profile in this
study supports the potential submission of an NDA for the VX-445 triple
combination regimen for patients with two F508del mutations.

Topline Data:

Data from this study showed a mean absolute improvement in ppFEV1 of
10.0 percentage points from baseline at week 4 when VX-445 was added in
patients who were already receiving tezacaftor in combination with
ivacaftor compared to those in whom placebo was added to tezacaftor and
ivacaftor (p<0.0001), which was the primary endpoint of the study. The
mean absolute within-group improvement in ppFEV1 from
baseline for those who received VX-445 in triple combination with
tezacaftor and ivacaftor was 10.4 percentage points at week 4. The mean
absolute within-group change in ppFEV1 from baseline for
those who received placebo, tezacaftor and ivacaftor was 0.4 percentage
points at week 4.

The VX-445 triple combination regimen was generally well tolerated in
this study. All of the 107 patients who received either the triple
combination of VX-445, tezacaftor and ivacaftor or placebo, tezacaftor
and ivacaftor completed the 4-week triple combination treatment period.

Open-Label Extension Study:

Similar to the study in people with one F508del mutation and one
minimal function mutation, all patients who completed treatment,
regardless of treatment assignment, were given the opportunity to enroll
in a rollover study where all patients received the VX-445 triple
combination regimen. All 107 of the patients who completed the study
elected to enter the open-label extension study.

About CF

CF is a rare, life-shortening genetic disease affecting approximately
75,000 people in North America, Europe and Australia. CF is caused by a
defective or missing CFTR protein resulting from mutations in the CFTR
gene. Children must inherit two defective CFTR genes — one from
each parent — to have CF. There are approximately 2,000 known mutations
in the CFTR gene. Some of these mutations, which can be
determined by a genetic test, or genotyping test, lead to CF by creating
non-working or too few CFTR proteins at the cell surface. The defective
function 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 mid-to-late 20s.

About Vertex

Vertex is a global biotechnology company that invests in scientific
innovation to create transformative medicines for people with serious
and life-threatening diseases. In addition to clinical development
programs in CF, Vertex has more than a dozen ongoing research programs
focused on the underlying mechanisms of other serious diseases.

Founded in 1989 in Cambridge, Mass., Vertex’s headquarters is now
located in Boston’s Innovation District. Today, the company has research
and development sites and commercial offices in the United States,
Europe, Canada, Australia and Latin America. Vertex is consistently
recognized as one of the industry’s top places to work, including being
named to Science magazine’s Top Employers in the life sciences ranking
for nine years in a row. For additional information and the latest
updates from the company, please visit www.vrtx.com.

Collaborative History with Cystic Fibrosis Foundation Therapeutics,
Inc. (CFFT)

Vertex initiated its CF research program in 2000 as part of a
collaboration with CFFT, the nonprofit drug discovery and development
affiliate of the Cystic Fibrosis Foundation. KALYDECO®
(ivacaftor), ORKAMBI® (lumacaftor/ivacaftor), SYMDEKO®
(tezacaftor/ivacaftor and ivacaftor), VX-659 and VX-445 were discovered
by Vertex as part of this collaboration.

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, Dr. Kewalramani’s statements in the third paragraph, and the
information provided regarding (i) the plan to seek global regulatory
approvals for a triple combination regimen in both F/MF and F/F
populations, (ii) the expected timing of the NDA and MAA submissions for
a triple combination therapy and (iii) the plan to provide additional
data regarding the selected regimen in the second quarter of 2019. 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 factors that could cause actual events or results to
differ materially from those indicated by such forward-looking
statements. Those risks and uncertainties include, among other things,
that the triple combination studies are ongoing, that the company could
experience unforeseen delays in submitting regulatory filings, that
regulatory authorities may not approve, or approve on a timely basis, a
triple-combination regimen due to safety, efficacy or other reasons, and
other risks listed under Risk Factors in Vertex’s annual report and
quarterly reports filed with the Securities and Exchange Commission and
available through the company’s website at www.vrtx.com.
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.

(VRTX-GEN)

Contacts

Investors:
Michael Partridge, 617-341-6108
or
Eric Rojas,
617-961-7205
or
Zach Barber, 617-341-6470

Media:
617-341-6992
mediainfo@vrtx.com

Source: Vertex Pharmaceuticals Incorporated


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