– Treatment with VX-548 led to statistically
significant improvement in pain compared to placebo as well as a
clinically meaningful reduction in pain from baseline in both the
abdominoplasty and bunionectomy randomized controlled trials –
– Treatment with VX-548 was also shown to be
effective in the single arm study in a broad range of surgical and
non-surgical pain conditions for up to 14 days –
– VX-548 was safe and well tolerated in all
three studies –
– Vertex plans to submit a New Drug Application
to the FDA by mid-2024 –
– Vertex to host investor call January 30 at
8:00 a.m. ET –
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced positive results from its Phase 3 program for the
selective NaV1.8 inhibitor, VX-548, in the treatment of
moderate-to-severe acute pain. The Phase 3 program included two
randomized, double-blind, placebo-controlled, pivotal trials, one
following abdominoplasty surgery and one following bunionectomy
surgery, as well as a single arm safety and effectiveness study
which enrolled patients with a broad range of surgical and
non-surgical pain conditions.
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the full release here:
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Figure 1: Mean NPRS Over Time in Phase 3
Study of Acute Pain Following Abdominoplasty (Graphic: Business
Wire)
Treatment with VX-548 following abdominoplasty or bunionectomy
surgery resulted in a statistically significant improvement on the
primary endpoint of the time-weighted sum of the pain intensity
difference from 0 to 48 hours (SPID48) compared to placebo as well
as a clinically meaningful reduction in pain from baseline at 48
hours on the Numeric Pain Rating Scale (NPRS) in both studies
(abdominoplasty: LS mean difference in SPID48 between VX-548 and
placebo = 48.4 (95% CI: 33.6, 63.1; P<0.0001); bunionectomy: LS
mean difference in SPID48 between VX-548 and placebo = 29.3 (95%
CI: 14.0, 44.6; P=0.0002)).
For the first key secondary endpoint, Vertex tested the
hypothesis that VX-548 was superior to hydrocodone
bitartrate/acetaminophen (HB/APAP) on SPID48 following
abdominoplasty surgery or bunionectomy surgery. Neither trial met
this key secondary endpoint (abdominoplasty: LS mean difference
between VX-548 and HB/APAP = 6.6 (95% CI: -5.4, 18.7; P=0.2781);
bunionectomy: LS mean difference between VX-548 and HB/APAP = -20.2
(95% CI: -32.7, -7.7; P=0.0016)).
The second key secondary endpoint in both trials was time to
meaningful pain relief defined as ≥2-point reduction in NPRS from
baseline compared to placebo. VX-548 had a more rapid onset to
meaningful pain relief than placebo in both the abdominoplasty and
bunionectomy trials. (The median time to meaningful pain relief was
8 hours for placebo in both studies compared to 2 hours in
abdominoplasty and 4 hours in bunionectomy for VX-548, with nominal
P<0.0001 and 0.0016, respectively.)
Other secondary endpoints in both trials were generally
consistent with the primary endpoint.
The Phase 3 single arm safety and effectiveness study evaluated
treatment with VX-548 for up to 14 days across a broad range of
other surgical and non-surgical acute pain conditions and
demonstrated favorable safety and tolerability, as well as
effectiveness as measured by a Patient Global Assessment (PGA) at
the end of treatment (83.2% of patients rated VX-548 as good, very
good, or excellent in treating pain).
VX-548 was safe and well tolerated in all three Phase 3 studies.
The majority of adverse events (AEs) were mild to moderate, and
there were no serious adverse events (SAEs) related to VX-548. In
general, AEs in the two randomized controlled trials were
consistent with the post-surgical setting. In the VX-548 arm, the
incidence of AEs was lower than placebo (patients with any AEs in
VX-548 and placebo arms: 50.0% and 56.3%, respectively, following
abdominoplasty, and 31.0% and 35.2%, respectively, following
bunionectomy).
“We are very pleased with the results from the VX-548 pivotal
program, which demonstrate a compelling and consistent combination
of efficacy and safety across multiple acute pain conditions and
settings. The VX-548 benefit-risk profile ideally positions it to
potentially fill the gap between medicines with good tolerability
but limited efficacy and opioid medicines with therapeutic efficacy
but known risks, including addictive potential,” said Reshma
Kewalramani, M.D., Chief Executive Officer and President of Vertex.
“With FDA Breakthrough and Fast Track Designations in hand, we are
working with urgency to file the New Drug Application for VX-548
and bring this non-opioid medicine to the millions of patients who
suffer from acute pain each year in the U.S.”
“As a physician treating patients suffering from pain for many
years, I know firsthand the critical need for new, efficacious and
safe treatment options,” said Jessica Oswald, M.D., M.P.H.,
Associate Physician in Emergency Medicine and Pain Medicine,
University of California San Diego, and Vertex Acute Pain Steering
Committee Member. “The Phase 3 safety and efficacy across the three
studies are impressive and demonstrate VX-548’s potential to change
the paradigm of pain management. I look forward to the potential of
having a new class of acute pain medicine — the first in more than
two decades — to use as an alternative to opioids to help the
millions of people impacted by acute pain.”
VX-548 Phase 3 Results in Patients
Undergoing Abdominoplasty
Efficacy Results
Patients aged 18 to 80 years with moderate or severe pain after
abdominoplasty surgery were eligible to participate in the trial.
1,118 patients were randomized and dosed with either VX-548
administered orally with an initial dose of 100 mg followed by 50
mg every 12 hours (at 12, 24 and 36 hours after the first dose),
hydrocodone bitartrate/acetaminophen (5 mg/325 mg administered
orally every 6 hours over 42 hours), or placebo.
Primary and Key Secondary Outcomes in Phase 3 Study of Acute
Pain Following Abdominoplasty
Placebo N=223
HB/APAP N=448
VX-548 N=447
Primary endpoint of SPID48 vs.
placebo
LS mean SPID48 (SE)
70.1 (6.1)
--
118.4 (4.3)
LS mean SPID48 difference from placebo
--
--
48.4
95% CI
--
--
(33.6, 63.1)
P value vs. placebo
--
--
<0.0001
First key secondary endpoint of SPID48
vs. HB/APAP
LS mean SPID48 (SE)
--
111.8 (4.3)
118.4 (4.3)
LS mean SPID48 difference from HB/APAP
--
--
6.6
95% CI
--
--
(-5.4, 18.7)
P value vs. HB/APAP
--
--
0.2781
Second key secondary endpoint of time
to ≥2-point reduction in NPRS from baseline vs. placebo
(minutes)
Median time
480
--
119
95% CI
(477, 705)
--
(90, 180)
P value* vs. placebo (Log-rank)
--
--
<0.0001
*P value is nominal; CI = confidence
interval; LS = least squares; SE = standard error.
Mean NPRS Over Time in Phase 3 Study of Acute Pain Following
Abdominoplasty [See Figure #1 at top of press release]
NPRS Reductions From Baseline at 48 Hours in Phase 3 Study of
Acute Pain Following Abdominoplasty
Placebo N=223
HB/APAP N=448
VX-548 N=447
Baseline NPRS, mean
7.5
7.4
7.3
Change from baseline in NPRS at 48
hours, mean
-2.3
-3.2
-3.4
% reduction from baseline in mean NPRS
at 48 hours
31%
43%
47%
Safety Results
VX-548 was generally well tolerated in this study. The majority
of adverse events (AEs) were mild to moderate, and there were no
serious adverse events (SAEs) related to VX-548.
In general, AEs were consistent with the post-surgical setting.
In the VX-548 arm, the incidence of AEs was lower than placebo
(patients with any AEs in VX-548 and placebo arms: 50.0% and 56.3%,
respectively).
AEs with an incidence ≥5% in any treatment groups (VX-548,
placebo, or HB/APAP, respectively) were nausea (19.0%, 25.2%,
32.8%), constipation (10.5%, 10.8%, 8.7%), headache (4.2%, 5.0%,
7.1%), dizziness (4.0%, 7.7%, 5.4%), and hypotension (2.5%, 6.8%,
3.6%).
VX-548 Phase 3 Results in Patients
Undergoing Bunionectomy
Efficacy Results
Patients aged 18 to 80 years with moderate or severe pain after
bunionectomy surgery were eligible to participate in the trial.
1,073 patients were randomized and dosed with either VX-548
administered orally with an initial dose of 100 mg followed by 50
mg every 12 hours (at 12, 24 and 36 hours after the first dose),
hydrocodone bitartrate/acetaminophen (5 mg/325 mg administered
orally every 6 hours over 42 hours) or placebo.
Primary and Key Secondary Outcomes in Phase 3 Study of Acute
Pain Following Bunionectomy
Placebo N=216
HB/APAP N=431
VX-548 N=426
Primary endpoint of SPID48 vs.
placebo
LS mean SPID48 (SE)
70.6 (6.3)
--
99.9 (4.5)
LS mean SPID48 difference from placebo
--
--
29.3
95% CI
--
--
(14.0, 44.6)
P value vs. placebo
--
--
0.0002
First key secondary endpoint of SPID48
vs. HB/APAP
LS mean SPID48 (SE)
--
120.1 (4.5)
99.9 (4.5)
LS mean SPID48 difference from HB/APAP
--
--
-20.2
95% CI
--
--
(-32.7, -7.7)
P value vs. HB/APAP
--
--
0.0016
Second key secondary endpoint of time
to ≥2-point reduction in NPRS from baseline vs. placebo
(minutes)
Median time
480
--
240
95% CI
(476, 716)
--
(117, 477)
P value* vs. placebo (Log-rank)
--
--
0.0016
*P value is nominal; CI = confidence
interval; LS = least squares; SE = standard error.
Mean NPRS Over Time in Phase 3 Study of Acute Pain Following
Bunionectomy [See Figure #2 at top of press release]
NPRS Reductions From Baseline at 48 Hours in Phase 3 Study of
Acute Pain Following Bunionectomy
Placebo N=216
HB/APAP N=431
VX-548 N=426
Baseline NPRS, mean
6.8
6.8
6.7
Change from baseline in NPRS at 48
hours, mean
-2.6
-3.6
-3.4
% reduction from baseline in mean NPRS
at 48 hours
38%
53%
51%
Safety Results
VX-548 was generally well tolerated in this study. The majority
of AEs were mild to moderate, and there were no SAEs.
In general, AEs were consistent with the post-surgical setting.
In the VX-548 arm, the incidence of AEs was lower than placebo
(patients with any AEs in VX-548 and placebo arms: 31.0% and 35.2%,
respectively).
AEs with an incidence ≥5% in any treatment groups (VX-548,
placebo, or HB/APAP, respectively) were nausea (8.2%, 10.6%,
14.4%), headache (4.9%, 9.3%, 10.4%), constipation (3.5%, 4.2%,
5.1%), and dizziness (3.5%, 5.1%, 5.3%).
VX-548 Phase 3 Safety and Effectiveness
Study Results
Vertex conducted an additional Phase 3 study in 256 patients to
evaluate safety and effectiveness in a broad range of surgical and
non-surgical moderate-to-severe acute pain conditions. Treatment
with VX-548 administered orally with an initial dose of 100 mg
followed by 50 mg every 12 hours for up to 14 days demonstrated
safety, tolerability and effectiveness across these
populations.
VX-548 was generally safe and well tolerated in this study. AEs
were mostly mild or moderate, and there were no SAEs related to
VX-548. The safety profile in this study was generally consistent
with randomized, controlled Phase 3 studies with VX-548.
Patient perception of VX-548 effectiveness in treating pain as
measured by a patient global assessment (PGA) at the end of
treatment showed 83.2% of patients reporting VX-548 as good, very
good, or excellent.
Next Steps for the Pain Portfolio
Vertex plans to submit a New Drug Application to the Food and
Drug Administration (FDA) by mid-2024 with the goal of achieving a
broad label in moderate-to-severe acute pain. VX-548 has secured
Breakthrough Therapy and Fast Track designations in the U.S. for
acute pain.
In addition, Vertex seeks to achieve a broad label in peripheral
neuropathic pain. In support of this goal, the company recently
reported positive Phase 2 results in painful diabetic peripheral
neuropathy (DPN) and expects to advance to pivotal development in
DPN with VX-548 following the end-of-phase 2 meeting with the FDA.
Vertex has also initiated a Phase 2 peripheral neuropathic pain
study of VX-548 in patients with painful lumbosacral radiculopathy,
or LSR, which is pain caused by impairment or injury to nerve roots
in the area of the lumbar spine.
In line with its portfolio strategy, Vertex continues to advance
preclinical and clinical development of additional NaV1.8 and
NaV1.7 inhibitors, for use alone or in combination, in acute and
neuropathic pain.
Conference Call and Webcast The company will host a
conference call and webcast at 8:00 a.m. ET on January 30, 2024. To
access the call, please dial (833) 630-2124 (U.S.) or +1 (412)
317-0651 (International) and reference the “Vertex Pharmaceuticals
Conference Call.”
The conference call will be webcast live and a link to the
webcast can be accessed through Vertex's website at www.vrtx.com in
the “Investors” section. To ensure a timely connection, it is
recommended that participants register at least 15 minutes prior to
the scheduled webcast. An archived webcast will be available on the
company's website.
About Acute Pain
Defined as pain lasting <3 months, acute pain is a disabling
condition that affects over 80 million people in the U.S. each
year. Due to limited treatment options, there is an unmet need in
acute pain management to improve the patient experience and reduce
the economic and societal burden.
About VX-548
VX-548 is an investigational oral, selective NaV1.8 pain signal
inhibitor that is highly selective for NaV1.8 relative to other NaV
channels. NaV1.8 is a voltage-gated sodium channel that plays a
critical role in pain signaling in the peripheral nervous system.
NaV1.8 is a genetically validated target for the treatment of pain,
and Vertex has previously demonstrated positive proof-of-concept
results and a well-tolerated profile with VX-548 in two Phase 2
studies of acute pain following abdominoplasty and bunionectomy
surgeries and in a Phase 2 study in painful diabetic peripheral
neuropathy, a type of peripheral neuropathic pain. Vertex’s
approach is to selectively inhibit NaV1.8 using small molecules
with the objective of creating a new class of medicines that have
the potential to provide effective relief of pain without the
limitations of opioids, including their addictive potential. VX-548
is one of the most recent molecules to enter clinical development
from Vertex’s portfolio of NaV1.8 pain signal inhibitors.
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 approved medicines that
treat the underlying causes of multiple chronic, life-shortening
genetic diseases — cystic fibrosis, sickle cell disease and
transfusion-dependent beta thalassemia — and continues to advance
clinical and research programs in these diseases. Vertex also has a
robust clinical pipeline of investigational therapies across a
range of modalities in other serious diseases where it has deep
insight into causal human biology, including APOL1-mediated kidney
disease, acute and neuropathic pain, type 1 diabetes, myotonic
dystrophy type 1 and alpha-1 antitrypsin deficiency.
Vertex was founded in 1989 and has its global headquarters in
Boston, with international headquarters in London. Additionally,
the company has research and development sites and commercial
offices in North America, Europe, Australia, Latin America and the
Middle East. Vertex is consistently recognized as one of the
industry's top places to work, including 14 consecutive years on
Science magazine's Top Employers list and one of Fortune’s 100 Best
Companies to Work For. For company updates and to learn more about
Vertex's history of innovation, visit www.vrtx.com or follow us on
LinkedIn, Facebook, Instagram, YouTube and Twitter/X.
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, statements by Reshma
Kewalramani, M.D., and Jessica Oswald, M.D., M.P.H., in this press
release, and statements regarding our beliefs about the potential
benefits of VX-548, our plans to submit a New Drug Application with
the FDA by mid-2024, our goal of achieving a broad label in
moderate to severe acute pain, our plans for a broad label in
peripheral neuropathic pain, our plans to advance to pivotal
development in DPN with VX-548 following the end-of-phase 2 meeting
with the FDA, and our plans to continue to advance preclinical and
clinical development of additional NaV1.8 and NaV1.7 inhibitors in
acute and neuropathic pain. 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 regulatory submissions may not be
completed on the anticipated timeline, or at all, that we may not
be able to achieve a broad pain label for VX-548, that data from
the company's research and development programs may not support
registration or further development of its compounds due to safety,
efficacy, 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 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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