- New data on povetacicept 80 mg SC Q4 weeks in
IgA nephropathy shows mean UPCR reduction from baseline of 66%
observed at 48 weeks, associated with stable renal function (eGFR)
and 63% achieving clinical remission --
- First proteinuria data on povetacicept in
primary membranous nephropathy shows mean UPCR reduction from
baseline of 62% at 24 weeks –
- Global Phase 3 RAINIER trial of povetacicept
in IgA nephropathy now underway –
– Enrollment and dosing ongoing in Phase 3
portion of the global Phase 2/3 pivotal clinical trial of inaxaplin
for the treatment of APOL1-mediated kidney disease –
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today
provided updates on multiple kidney diseases in its pipeline
including IgA nephropathy (IgAN), primary membranous nephropathy
(pMN), and APOL1-mediated kidney disease (AMKD). These updates
demonstrate the transformative potential of Vertex’s
investigational therapies in multiple serious kidney diseases, and
include positive new data on povetacicept, a dual inhibitor of the
BAFF and APRIL pathways, in IgAN and pMN, presented at the American
Society of Nephrology’s (ASN) Kidney Week Congress on October 23-27
in San Diego, California.
“We are very pleased with the broadening of our innovative
pipeline in renal medicine which now spans programs in AMKD, IgAN,
pMN and polycystic kidney disease,” said Carmen Bozic, M.D.,
Executive Vice President, Global Medicines Development and Medical
Affairs, and Chief Medical Officer at Vertex. “The new data in IgAN
and pMN we shared at this year’s ASN congress continue to reinforce
povetacicept as a potential best-in-class therapy and demonstrate
its potential as a pipeline-in-a-product. We also continue to make
progress in AMKD and autosomal dominant polycystic kidney disease
(ADPKD) where we are advancing the first potential treatments to
address the underlying cause of these diseases.”
Povetacicept in IgAN
Vertex presented data on 54 patients with IgAN who received
povetacicept 80 mg or 240 mg subcutaneously every 4 weeks (SC Q4W).
Treatment with povetacicept 80 mg SC Q4W demonstrated a clinically
meaningful decrease in proteinuria, with a mean 66% reduction from
baseline in urine protein to creatinine ratio at 48 weeks (UPCR;
n=8) associated with stable renal function over 48 weeks as
assessed by estimated glomerular filtration rate (eGFR). By 48
weeks, 63% (5 out of 8) of study participants achieved clinical
remission, defined as UPCR <0.5 g/g, negative hematuria and
stable renal function (<25% reduction in eGFR from
baseline).
Treatment with povetacicept 240 mg SC Q4W was associated with
similar improvements in proteinuria along with stable renal
function.
Both doses have been well tolerated in patients with IgAN. The
majority of adverse events (AEs) were mild or moderate in severity,
and there were no serious adverse events (SAEs) related to
povetacicept.
Vertex has now initiated RAINIER, a global Phase 3 clinical
trial of povetacicept 80 mg in IgAN.
A poster presentation #FR-PO854 entitled “Results from Longer
Follow-Up with Povetacicept, an Enhanced Dual BAFF/APRIL
Antagonist, in IgA Nephropathy (RUBY-3 Study)” was presented during
the poster session on October 25 from 10:00 a.m. to 12:00 p.m.
PDT.
Povetacicept in pMN
Vertex also presented emerging data in patients with pMN who
received povetacicept 80 mg SC Q4W, with three patients having
completed at least 24 weeks of treatment. Treatment with
povetacicept demonstrated a mean 62% reduction from baseline in
UPCR at 24 weeks, associated with stable renal function. By week
24, 67% (2 out of 3) study participants had achieved partial
clinical remission, defined as UPCR <3.5 g/g and >50%
reduction in UPCR from baseline. Anti-PLA2R1 autoantibodies, which
are a marker of disease activity and associated with clinical
outcomes, decreased from baseline by a mean of 87% at week 20.
Povetacicept was well tolerated in patients with pMN, with AEs
that were mild or moderate in severity. There were no SAEs related
to povetacicept.
A poster presentation #TH-PO589 entitled “Updated Results with
Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Primary
Membranous Nephropathy (RUBY-3 Study)” was presented during the
poster session on October 24 from 10:00 a.m. to 12:00 p.m. PDT.
AMKD
Vertex is developing inaxaplin, a potential first-in-class,
investigational, oral small molecule inhibitor of APOL1, with the
goal of targeting the underlying cause of AMKD. Enrollment and
dosing are ongoing in the Phase 3 portion of the global Phase 2/3
pivotal AMPLITUDE clinical trial of inaxaplin.
Vertex has the following AMKD poster presentations at ASN:
- Poster presentation #TH-P01203 entitled “AMPLITUDE: A Phase 2/3
Adaptive Trial of Inaxaplin in APOL1-mediated Kidney Disease” was
presented during the poster session on October 24 from 10:00 a.m.
to 12:00 p.m. PDT.
- Poster presentation #SA-PO701 entitled “Small Molecule APOL1
Channel Inhibitor Reduces Proteinuria, Rescues Podocyte Injury, and
Reverses eGFR Decline in an APOL1-Mediated Kidney Disease Mouse
Model” will be presented during the poster session on October 26
from 10:00 a.m. to 12:00 p.m. PDT.
- Poster presentation #SA-PO700 entitled “Small Molecule
Inhibition of APOL1 Channel Activity Protects Podocytes from
Mitochondrial Dysfunction, Cell Death and Barrier Disruption
Induced by APOL1 Risk Variants” will be presented during the poster
session on October 26 from 10:00 a.m. to 12:00 p.m. PDT.
All accepted abstracts are available online on the ASN
website.
About IgA Nephropathy (IgAN)
IgAN is a serious, progressive, life-threatening, B
cell-mediated chronic kidney disease that is the most common cause
of primary (idiopathic) glomerulonephritis, affecting people
worldwide including approximately 130,000 people in the U.S. IgAN
results from deposition of circulating immune complexes consisting
of immunoglobulins and galactose-deficient immunoglobulin A
(Gd-IgA1) in the renal glomerular mesangium, triggering kidney
injury and fibrosis. A high percentage of people with IgAN progress
to end-stage renal disease. There are no approved therapies that
specifically target the underlying cause of IgAN.
About RAINIER
RAINIER is a global Phase 3 pivotal trial of povetacicept 80 mg
vs. placebo on top of standard of care in approximately 480 people
with IgAN. The study is designed to have a pre-planned interim
analysis evaluating UPCR for the povetacicept arm versus placebo
after a certain number of patients reach 36 weeks of treatment. If
positive, the interim analysis may serve as the basis for Vertex to
seek accelerated approval in the U.S. Final analysis will occur at
two years of treatment, with a primary endpoint of total eGFR slope
through Week 104.
About Primary Membranous Nephropathy (pMN)
Primary membranous nephropathy is a serious, progressive,
life-threatening B cell-mediated chronic kidney disease affecting
people worldwide, with approximately 60,000 people diagnosed in the
U.S. pMN causes a patient’s immune system to damage the glomeruli
and may cause progressive loss of kidney function. There are no
approved therapies that specifically target the underlying cause of
pMN.
About RUBY-3
RUBY-3 is an ongoing, multiple ascending dose, multi-cohort,
open label, Phase 1/2 basket study of povetacicept in autoimmune
glomerulonephritis, including IgAN, pMN, lupus nephritis and
ANCA-associated vasculitis with glomerulonephritis where
povetacicept is being administered subcutaneously for up to 104
weeks.
About Povetacicept
Povetacicept is a dual antagonist of the BAFF (B cell activating
factor) and APRIL (a proliferation inducing ligand) cytokines,
which play key roles in pathogenesis of multiple autoimmune
diseases via their roles in the activation, differentiation and/or
survival of B cells, T cells and innate immune cells. Based upon an
engineered TACI (transmembrane activator and CAML interactor)
domain, povetacicept has higher binding affinity and greater
potency in preclinical studies versus other inhibitors of BAFF
and/or APRIL alone and has demonstrated potential best-in-class
efficacy in a clinical trial in patients with IgA nephropathy and
primary membranous nephropathy. Povetacicept is also in development
for multiple serious diseases including other autoimmune kidney
diseases and autoimmune cytopenias.
About APOL1-Mediated Kidney Disease (AMKD)
AMKD is a genetic kidney disease affecting approximately 100,000
people in the U.S. and Europe. AMKD is caused by two variants of
the APOL1 gene, which exert a toxic effect on kidney cells, leading
to cell injury, cell death and damage to glomeruli (which filter
blood to the kidney). Even after treatment with currently available
therapies, people with AMKD often progress to kidney failure.
Kidney failure is treated with frequent, long-term dialysis or a
kidney transplant. Both require lifelong treatment and follow-up
and carry a high mortality risk. There are currently no
approved treatments that address the underlying cause of AMKD.
About Inaxaplin
Inaxaplin is a potential first-in-class, investigational small
molecule inhibitor of APOL1, and the first investigational therapy
aimed at treating the underlying cause of AMKD.
About AMPLITUDE
AMPLITUDE is a global Phase 2/3 pivotal trial of inaxaplin for
the treatment of AMKD, in which a 45 mg once daily oral dose is
compared to placebo, on top of standard of care. The study is
designed to have a pre-planned interim analysis at Week 48
evaluating estimated glomerular filtration rate (eGFR) slope, a
measure of kidney function, supported by a percent change from
baseline in proteinuria, in the inaxaplin arm versus placebo. If
positive, the interim analysis may serve as the basis for Vertex to
seek accelerated approval in the U.S. Enrollment and dosing are
ongoing in the Phase 3 portion of the study.
About Autosomal Dominant Polycystic Kidney Disease
(ADPKD)
ADPKD is the most common inherited kidney disease and one of the
most common severe Mendelian genetic diseases, affecting
approximately 250,000 diagnosed people in the U.S. and Europe. As
an autosomal dominant disease, one affected parent can pass on the
disease to their children.
In most cases, ADPKD is caused by variants in the PKD1 and PKD2
genes, which express proteins known as polycystins. The majority of
ADPKD patients (~80%) have a variant in the PKD1 gene, resulting in
a loss of function of polycystin 1 (PC1). This leads to the
proliferation of kidney epithelial cells, increased fluid secretion
and the formation and expansion of numerous fluid-filled cysts. The
progressive cyst formation causes an increase in kidney size and
decline in kidney function. Around half of patients with ADPKD
experience kidney failure by the age of 60. Kidney cysts can also
lead to severe abdominal pain, cyst infection, blood in the urine
and kidney stones, all of which significantly impair quality of
life.
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.
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, the statements by Carmen
Bozic, M.D., in this press release, and statements regarding
Vertex’s expectations and plans for the global Phase 3 RAINIER
study of povetacicept, including the potential for an interim
analysis to serve as the basis to seek accelerated approval in the
U.S., and expectations and plans for the Phase 3 portion of the
clinical trial of inaxaplin, including the potential for an interim
analysis to serve as the basis to seek accelerated approval in the
U.S. While we believe 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 company's development programs may not support
registration or further development of its compounds due to safety,
efficacy, and other reasons, 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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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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