- In the ALIGN study, atrasentan, in addition to supportive
care with a renin-angiotensin system (RAS) inhibitor, demonstrated
a statistically significant 36.1% proteinuria (protein in urine)
reduction vs. placebo + supportive care at 36 weeks1
- Endothelin A (ETA) receptor activation contributes to
elevated proteinuria in IgAN2-5; atrasentan is a potent,
selective ETA receptor antagonist with potential to reduce
persistent proteinuria and preserve kidney function for a broad
patient population1
- IgAN is a heterogeneous, progressive, rare kidney disease
with a need for effective, targeted therapies6,7; up to
30% of patients with persistent proteinuria (≥1 g/day) progress to
kidney failure within 10 years8
- Through its rare kidney disease portfolio, Novartis is
committed to exploring a range of treatment options with different
modes of action to slow IgAN progression
EAST
HANOVER, N.J., May 25, 2024
/PRNewswire/ -- Novartis today presented results from a
pre-specified interim analysis of the Phase III ALIGN study of
atrasentan, an investigational oral selective endothelin A (ETA)
receptor antagonist, in patients with IgA nephropathy
(IgAN)1. Patients treated with atrasentan, in addition
to supportive care (maximally tolerated and stable dose of a
renin-angiotensin system [RAS] inhibitor), achieved a 36.1%
(p<0.0001) reduction in proteinuria (as measured by 24-hour
urine protein to creatinine ratio [UPCR]) at 36 weeks when compared
to placebo on top of supportive care1. The results were
presented during a late-breaking clinical trials session at the
European Renal Association (ERA) Congress1. The study
also showed atrasentan has a favorable safety profile consistent
with previously reported data1,9.
Proteinuria reduction is a recognized surrogate marker
correlating with delaying progression to kidney failure and has
been used as an endpoint in IgAN clinical trials to support
accelerated regulatory approvals10. US FDA
submission for atrasentan in IgAN is on track for the first half of
2024.
"For those living with IgAN and their families, the disease can
have a significant impact not only physically, but also mentally.
When my son Eddie was diagnosed with IgAN 20 years ago, there were
no FDA-approved medicines developed to treat IgAN. That was as
devastating as the diagnosis itself because we felt completely in
the dark about how to manage the condition," said Bonnie Schneider, Director and Co-Founder,
IgAN Foundation. "It's a disease
that affects people differently, and what works for one person may
not work for another. We're pleased to see ongoing research into
different treatments and are excited for a future where the
community will have options to meet their individual
needs."
The ALIGN study continues in a blinded manner, and therefore
only limited interim analysis results can be
presented11,12. The final analysis, including the key
secondary endpoint of change from baseline in estimated glomerular
filtration rate (eGFR) at 136 weeks, and the results in
participants receiving a sodium-glucose co-transporter-2 (SGLT2)
inhibitor as background care in an exploratory cohort, is expected
in 202611,12.
"ETA receptor activation causes proteinuria, which is usually
one of the first clinical signs of IgAN. Patients with persistent
proteinuria have a poorer prognosis and are more likely to progress
to kidney failure," said Professor Hiddo Heerspink, Professor of
Clinical Trials and Personalized Medicine at the Department of
Clinical Pharmacy and Pharmacology at the University Medical Center
Groningen and ALIGN blinded Steering Committee Chair. "We
need targeted treatment options that can support patients with IgAN
across the care pathway. These data from the ALIGN study further
demonstrate the ability of atrasentan to significantly reduce
proteinuria and, if approved, its potential to become a new
foundational treatment for people living with IgAN that can be
seamlessly added to current supportive therapy."
"Atrasentan has the potential to help transform how IgAN is
managed for many people living with this complex illness," said
David Soergel, M.D., Global Head,
Cardiovascular, Renal and Metabolism Development Unit, Novartis.
"Our multi-product IgAN portfolio aims to address the needs of a
broad, heterogenous patient population with different modes of
action to target distinct drivers of the disease, with the ultimate
goal of improving patient care in this therapeutic area."
At ERA, Novartis is also presenting new data across its rare
disease portfolio, including 6-month data for Fabhalta®
(iptacopan) in C3 glomerulopathy (C3G) from the Phase III
APPEAR-C3G study, long-term 33-month efficacy and safety data for
Fabhalta in C3G from the Phase II extension study, additional data
for Fabhalta in IgAN from the 9-month interim analysis of the Phase
III APPLAUSE-IgAN study, 1-year Phase I/II data for investigational
zigakibart in IgAN, and data from real-world studies in C3G and
atypical hemolytic uremic syndrome (aHUS)13-16.
About ALIGN
The ALIGN study (NCT04573478) is a global,
randomized, multicenter, double-blind, placebo-controlled
Phase III clinical trial comparing the efficacy and safety of
atrasentan versus placebo in patients with IgAN at risk of
progressive loss of kidney function11,12. In total, 340
patients with biopsy-proven IgAN with baseline total proteinuria ≥1
g/day despite optimized RAS inhibitor treatment were
randomized to receive once-daily oral doses of atrasentan (0.75 mg)
or placebo for approximately 2.5 years (132 weeks)11,12.
Patients continue receiving a maximally tolerated and stable dose
of a RAS inhibitor as supportive care (unless they are unable to
tolerate RAS inhibitor therapy)11,12. An additional
group of 64 patients receiving a stable dose of SGLT2 inhibitor for
at least 12 weeks have also been
enrolled11,12.
The primary efficacy endpoint of the study is change in
proteinuria as measured by 24-hour UPCR from baseline to 36
weeks11,12. Secondary and exploratory objectives include
evaluating the change in kidney function from baseline to 136 weeks
as measured by eGFR, as well as safety and
tolerability11,12.
About atrasentan
Atrasentan is an investigational potent and selective oral ETA
receptor antagonist, currently in Phase III development for IgAN
and early-stage development for other rare kidney
diseases1,11,12,17. Activation of the ETA receptor
contributes to elevated proteinuria, which is associated with
kidney damage, fibrosis and loss of kidney function in
IgAN2-5. Atrasentan has potential to be added to current
supportive therapy to reduce persistent proteinuria and preserve
kidney function for a broad patient population1.
Preclinical models have also suggested that atrasentan may reduce
inflammation and fibrosis in IgAN18-21.
About IgA nephropathy (IgAN)
IgAN is a heterogeneous, progressive, rare kidney
disease6. Each year, approximately 25 people per million
worldwide are newly diagnosed with
IgAN22.
Up to 30% of people who have IgAN with persistent higher levels
of proteinuria (≥1 g/day) may progress to kidney failure within 10
years8. There is a need for effective, targeted
therapies for IgAN that can help slow or prevent progression to
kidney failure6,7,23.
Novartis commitment in rare kidney diseases
At Novartis, our journey in nephrology began more than 40 years ago
when the development and introduction of cyclosporine helped
reimagine the field of transplantation and immunosuppression. We
continue today with the same bold ambition to transform the lives
of people living with kidney diseases.
Through our portfolio, we are exploring potential therapeutic
options to address the current unmet needs of people living with
rare diseases, including IgAN, C3G, aHUS, immune complex
membranoproliferative glomerulonephritis (IC-MPGN) and lupus
nephritis (LN). Innovative treatment options that target the
underlying causes of these diseases may preserve kidney function
and help people live longer without the need for dialysis or
transplantation.
IgAN is a heterogeneous disease presenting with a variety of
clinical manifestations, phenotypes, and variable speeds of
progression6. In addition to atrasentan, Novartis is
advancing the development of two other therapies in IgAN with
highly differentiated mechanisms of action: Fabhalta, an
investigational oral Factor B inhibitor of the alternative
complement pathway, and zigakibart, an investigational
subcutaneously administered anti-APRIL monoclonal antibody, which
are both in Phase III development24-26. Through our IgAN
pipeline, we are committed to creating a portfolio of innovative
medicines that improve and extend the lives of people living with
kidney disease.
Disclaimer
This press release contains forward-looking statements within the
meaning of the United States Private Securities Litigation Reform
Act of 1995. Forward-looking statements can generally be identified
by words such as "potential," "can," "will," "plan," "may,"
"could," "would," "expect," "anticipate," "look forward,"
"believe," "committed," "investigational," "pipeline," "launch," or
similar terms, or by express or implied discussions regarding
potential marketing approvals, new indications or labeling for the
investigational or approved products described in this press
release, or regarding potential future revenues from such products.
You should not place undue reliance on these statements. Such
forward-looking statements are based on our current beliefs and
expectations regarding future events, and are subject to
significant known and unknown risks and uncertainties. Should one
or more of these risks or uncertainties materialize, or should
underlying assumptions prove incorrect, actual results may vary
materially from those set forth in the forward-looking statements.
There can be no guarantee that the investigational or approved
products described in this press release will be submitted or
approved for sale or for any additional indications or labeling in
any market, or at any particular time. Nor can there be any
guarantee that such products will be commercially successful in the
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could be affected by, among other things, the uncertainties
inherent in research and development, including clinical trial
results and additional analysis of existing clinical data;
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global trends toward health care cost containment, including
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undertake any obligation to update any forward-looking statements
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future events or otherwise.
About Novartis
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professionals and societies are empowered in the face of serious
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