– Treatment with the highly selective NaV1.8
pain signal inhibitor suzetrigine met the primary endpoint with a
statistically significant and clinically meaningful 2.02 point
within-group reduction from baseline in the Numeric Pain Rating
Scale (NPRS) –
– Placebo arm showed similar within-group
reduction in NPRS –
– Suzetrigine was generally well tolerated
–
– Advancement to Phase 3 in painful lumbosacral
radiculopathy planned, pending discussions with regulators –
– Vertex to host investor call on December 19
at 8:00 a.m. ET –
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
announced results from its Phase 2 study of suzetrigine, an
investigational, oral, highly selective NaV1.8 pain signal
inhibitor in people with painful lumbosacral radiculopathy (LSR).
The study met its primary endpoint with statistically significant
and clinically meaningful reduction in pain on the numeric pain
rating scale (NPRS).
Efficacy Results
The study’s primary endpoint was a within-group change from
baseline in the weekly average of daily leg pain intensity on the
NPRS at Week 12. This 11-point scale ranges from 0 (no pain) to 10
(worst pain imaginable).
The suzetrigine arm showed a statistically significant and
clinically meaningful within-group reduction from baseline in pain
with a mean change in NPRS at Week 12 of -2.02.
The study also included a placebo reference arm which showed a
similar within-group reduction from baseline in pain with a mean
change in NPRS at Week 12 of -1.98. The study was not designed nor
powered for statistical comparison between suzetrigine and
placebo.
Suzetrigine N =
102
Placebo N = 100
Baseline NPRS
Mean NPRS (SD)
6.33 (1.22)
6.05 (1.07)
Change in NPRS from baseline at Week
12
LS mean
-2.02
-1.98
95% CI
(-2.40, -1.64)
(-2.36, -1.60)
P value
<0.0001
<0.0001
Secondary and other endpoints were consistent with the study’s
primary endpoint.
Vertex also conducted post-hoc analyses to further evaluate the
efficacy results. These showed that there was variability in the
placebo response across study sites, a recognized issue in pain
trials. In the ~40% of sites that had lower placebo responses, the
suzetrigine arm within-group reduction in pain was similar to the
overall study and had greater separation from the placebo arm.
These analyses suggest that trial design innovation may better
control the placebo response and separate the treatment effect of
suzetrigine from placebo in future studies, which Vertex will
incorporate as it designs the pivotal program.
Safety Results
Suzetrigine was generally well tolerated in the study. The
incidence of adverse events (AEs) was 22.9% in the suzetrigine arm
and 32.4% in the placebo arm. In both treatment arms, most AEs were
mild to moderate. There were no serious adverse events (SAEs)
related or possibly related to suzetrigine. There were no AEs
leading to treatment discontinuation in patients treated with
suzetrigine.
Suzetrigine N = 109
n (%)
Placebo N = 108
n (%)
Subjects with any AEs
25 (22.9)
35 (32.4)
Subjects with AEs by strongest
relationship
Not related
16 (14.7)
20 (18.5)
Unlikely related
1 (0.9)
6 (5.6)
Possibly related
6 (5.5)
8 (7.4)
Related
2 (1.8)
1 (0.9)
Subjects with AEs by maximum
severity
Grade 1/Mild
15 (13.8)
17 (15.7)
Grade 2/Moderate
10 (9.2)
17 (15.7)
Grade 3/Severe
0
1 (0.9)
Grade 4/Life-threatening
0
0
Grade 5/Death
0
0
Subjects with serious AEs
1 (0.9)
2 (1.9)
Subjects with AEs leading to treatment
discontinuation
0
1 (0.9)
Subjects with AEs leading to
death
0
0
“Suzetrigine has again demonstrated its potential to fill an
important unmet need in the treatment of pain. Today's LSR results
are consistent with previous studies of this pain signal inhibitor
in terms of showing a meaningful treatment effect across pain
conditions and a favorable safety profile,” said Carmen Bozic,
M.D., Executive Vice President, Global Medicines Development and
Medical Affairs, and Chief Medical Officer at Vertex. “We did not
see separation between the suzetrigine and the placebo arms. Yet
our post-hoc analyses suggest that this could be due to the high
placebo response in this study. We remain committed to studying LSR
and innovating our Phase 3 study design to control for the placebo
effect as we advance suzetrigine into pivotal development for this
condition.”
“The suzetrigine Phase 2 results clearly show reduced pain
intensity from baseline in the active drug arm, and the potential
for suzetrigine to fill an unmet need in relieving LSR pain, a
heterogeneous condition that is notoriously difficult to treat,”
said Christine Sang, M.D., M.P.H., FASA, Director, Translational
Pain Research, Brigham and Women's Hospital, Associate Professor of
Anesthesia, Harvard Medical School, co-chair of Vertex’s Peripheral
Neuropathic Pain steering committee, and lead principal
investigator on the study. “Managing the placebo response in pain
trials is a complex challenge. We look forward to innovating in
clinical trial design, including for the pivotal study, with the
aim of bringing a potentially safe and effective treatment to
patients suffering from LSR."
Next Steps for the Pain Portfolio
Neuropathic Pain
Vertex plans to advance suzetrigine into pivotal development for
painful LSR following discussions with regulators on the study
design and regulatory package. The company will apply learnings
from analysis of the full Phase 2 data set and post-hoc analyses to
inform the Phase 3 study design.
Earlier this year, Vertex initiated its suzetrigine pivotal
program in painful diabetic peripheral neuropathy (DPN), another
type of peripheral neuropathic pain (PNP). That study is
ongoing.
Acute Pain
Additionally, as previously announced, suzetrigine is under FDA
review for the treatment of moderate-to-severe acute pain. The
agency granted priority review and assigned a Prescription Drug
User Fee Act (PDUFA) target action date of January 30, 2025.
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 Thursday, December 19, 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 the Phase 2 Suzetrigine Lumbosacral Radiculopathy (LSR)
Study
This phase 2, 12-week, randomized, double-blind,
placebo-controlled study evaluated the efficacy and safety of
suzetrigine in treating patients with painful LSR. A total of 218
patients were enrolled in the study and randomized 1:1 with
suzetrigine or placebo. The primary endpoint was the within-group
change from baseline in the weekly average of daily leg pain
intensity on a numeric pain rating scale (NPRS) at Week 12. The
study also included a placebo reference arm; however, the study was
not designed nor powered for comparison between suzetrigine and
placebo.
Secondary endpoints assessed the within-group change from
baseline in the weekly average of the daily sleep interference
scale at Week 12 and safety and tolerability. By blocking the pain
signal from the peripheral sensory neurons, Vertex believes that
suzetrigine may alleviate the suffering for millions of patients
with painful LSR.
About Painful Lumbosacral Radiculopathy (LSR)
Painful lumbosacral radiculopathy, or LSR, is one of the most
common causes of peripheral neuropathic pain. It is pain caused by
impairment of nerve roots in the area of the lumbar spine. It often
results in radiating pain along the distribution of the impacted
nerve in the body, and patients can experience back and leg pain,
sensory issues or motor dysfunction. Common causes of LSR include
nerve compression from a herniated disk, or arthritic or
degenerative changes in the area of the lower spine. LSR is a
neuropathic pain condition because the impacted nerve roots are
part of the peripheral nervous system and not part of the spinal
cord. Millions of patients suffer from pain due to LSR every
year.
About Suzetrigine
Suzetrigine is an investigational oral, highly selective pain
signal inhibitor that is selective for NaV1.8 relative to other NaV
channels. NaV1.8 is a voltage-gated sodium channel that is
selectively expressed in peripheral pain-sensing neurons
(nociceptors), where its role is to transmit pain signals (action
potentials). Vertex’s approach is to selectively inhibit NaV1.8
using small molecules with the objective of creating a new class of
pain signal inhibitors that have the potential to provide effective
relief of pain without the limitations of currently available
therapies, including the addictive potential of opioids.
Suzetrigine has demonstrated a favorable benefit/risk profile in
multiple Phase 2 and Phase 3 studies in patients with
moderate-to-severe acute pain and has been granted FDA Fast Track
and Breakthrough Therapy designations in moderate-to-severe acute
pain in the U.S. It is currently under priority review by the FDA
for the treatment of moderate-to-severe acute pain with a
Prescription Drug User Fee Act (PDUFA) target action date of
January 30, 2025. The Phase 3 pivotal program for suzetrigine in
patients with painful diabetic peripheral neuropathy is ongoing,
and the company plans to advance its pivotal program evaluating
suzetrigine in patients with painful lumbosacral radiculopathy
pending discussions with regulators. Suzetrigine is investigational
and has not been approved by any health authority.
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 acute and neuropathic
pain, APOL1-mediated kidney disease, IgA nephropathy, primary
membranous nephropathy, autosomal dominant polycystic kidney
disease, type 1 diabetes and myotonic dystrophy type 1.
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 15 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 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 Carmen Bozic,
M.D., and Christine Sang, M.D., M.P.H., FASA, in this press
release, and statements regarding Vertex’s beliefs about the
potential benefits of suzetrigine for patients with LSR, plans to
advance suzetrigine to Phase 3 pending discussions with regulators,
plans and expectations for the design of the pivotal program, plans
to apply learnings from the Phase 2 data and post-hoc analyses to
inform the Phase 3 study design, including beliefs that trial
design innovation may better control the placebo response and
separate the treatment effect of suzetrigine from placebo in future
studies, 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 data from the clinical program
evaluating suzetrigine as a treatment for LSR may not support
registration or further development of its compounds due to safety,
efficacy or other reasons, that discussions with regulators may
have different outcomes than the company anticipates, 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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Vertex Pharmaceuticals Incorporated Investors:
InvestorInfo@vrtx.com Susie Lisa, CFA: +1 617-341-6108 or Miroslava
Minkova: +1 617-341-6135 Media: mediainfo@vrtx.com or
International: +44 20 3204 5275 or U.S.: 617-341-6992 or Heather
Nichols: +1 617-839-3607
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