* 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 weeks(1
    )
  * Endothelin A (ETA) receptor activation contributes to elevated proteinuria

in IgAN(2-5); atrasentan is a potent, selective ETA receptor antagonist with

    potential to reduce persistent proteinuria and preserve kidney function for
    a broad patient population(1
    )
  * IgAN is a heterogeneous, progressive, rare kidney disease with a need for
    effective, targeted therapies(6,7); up to 30% of patients with persistent
    proteinuria (>=1 g/day) progress to kidney failure within 10 years(8
    )
  * 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

Basel, May 25, 2024 - 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=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 enrolled(11,12).
The primary efficacy endpoint of the study is change in proteinuria as measured
by 24-hour UPCR from baseline to 36 weeks(11,12). 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 tolerability(11,12).
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 diseases(1,11,12,17). Activation of the ETA
receptor contributes to elevated proteinuria, which is associated with kidney
damage, fibrosis and loss of kidney function in IgAN(2-5). Atrasentan has
potential to be added to current supportive therapy to reduce persistent
proteinuria and preserve kidney function for a broad patient population(1).
Preclinical models have also suggested that atrasentan may reduce inflammation
and fibrosis in IgAN(18-21).
About IgA nephropathy (IgAN)
IgAN is a heterogeneous, progressive, rare kidney disease(6). Each year,
approximately 25 people per million worldwide are newly diagnosed with IgAN(22).
Up to 30% of people who have IgAN with persistent higher levels of proteinuria
(>=1 g/day) may progress to kidney failure within 10 years(8). There is a need
for effective, targeted therapies for IgAN that can help slow or prevent
progression to kidney failure(6,7,23).
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 progression(6). 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 development(24-26). 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
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inherent in research and development, including clinical trial results and
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update any forward-looking statements contained in this press release as a
result of new information, future events or otherwise.
About Novartis
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