* Secondary endpoint data for estimated glomerular filtration rate (eGFR)

    showed numerical improvement over 6 months vs. placebo(1); additional 6-
    month open-label data to be presented at a future medical meeting(2,3)
  * Fabhalta showed a favorable safety profile with no new safety signals(1)
  * C3G, an ultra-rare kidney disease caused by alternative complement pathway
    overactivation, progresses to kidney failure in ?50% of patients within 10
    years(4-7); currently there are no treatments approved for C3G(7-9 )
  * Fabhalta, an oral Factor B inhibitor of the alternative complement pathway,
    selectively targets the underlying cause of C3G(1); late-stage development
    program ongoing across several other rare diseases(10-13)

Basel, May 25, 2024 - Novartis today presented results from the 6-month, double-
blind period of the Phase III APPEAR-C3G study of Fabhalta(®) (iptacopan) at the
late-breaking clinical trials session of the European Renal Association (ERA)
Congress(1). Patients treated with Fabhalta in addition to supportive care
achieved a 35.1% (p=0.0014) reduction in proteinuria (as measured by 24-hour
urine protein to creatinine ratio (UPCR)) at 6 months when compared to placebo
on top of supportive care(1). In many kidney diseases, proteinuria reduction is
an increasingly recognized surrogate marker correlating with delaying
progression to kidney failure(14,15).
Fabhalta is an oral Factor B inhibitor of the alternative complement pathway
being investigated in adult patients with C3 glomerulopathy (C3G)(1-3).
Regulatory submissions, including to the FDA and EMA, for the adult C3G
indication are planned for the second half of 2024.
"C3G is an overlooked and devastating illness that often strikes when people are
young. The prognosis for patients with C3G is poor, and around half of the
affected patients progress to kidney failure requiring dialysis or transplant
within 10 years of being diagnosed," said Marianne Silkjær Nielsen, Founder of
CompCure, a Danish non-profit association committed to improving outcomes for
individuals with C3G and immune complex membranoproliferative glomerulonephritis
(IC-MPGN). "Currently there are no therapies approved for C3G, but research into
potential new treatments developed specifically for this disease gives us hope
that we can improve outcomes for patients and blunt its emotional, physical and
social effects."
Additional data on the secondary endpoint of estimated glomerular filtration
rate (eGFR), a measure of kidney function, showed a numerical improvement of
+2.2 mL/min/1.73 m(2) (p=0.1945) over 6 months with Fabhalta compared to
placebo(1). The study also showed Fabhalta has a favorable safety profile with
no new safety signals(1).
"This is an exciting milestone for patients and the potential future management
of C3G. The hallmark of C3G is overactivation of part of the immune system
called the alternative complement pathway, which damages the kidneys and leads
to severe loss of kidney function in many patients. Currently used treatments
don't address the underlying biology of C3G and often come with significant side
effects that add to the burden of the illness," said Professor David Kavanagh,
Professor of Complement Therapeutics & Honorary Consultant Nephrologist at the
Faculty of Medical Sciences at Newcastle University and APPEAR-C3G Steering
Committee Member. "Fabhalta is the first potential treatment that targets the
alternative complement pathway in C3G, and its impact on measures of kidney
damage and kidney function in this study, in addition to its safety profile, is
encouraging for patients and the clinical community."
The APPEAR-C3G study continues with an additional 6-month, open-label period
following the 6-month double-blind period, in which all patients receive
Fabhalta, including those previously receiving placebo(2,3). These data will be
presented at an upcoming medical meeting when available.
At ERA, Novartis is also presenting new data across its rare disease portfolio,
including results for investigational atrasentan in IgA nephropathy (IgAN) from
the 36-week interim analysis of the Phase III ALIGN study, additional data for
Fabhalta in IgAN from the 9-month interim analysis of the Phase III APPLAUSE-
IgAN study, long-term 33-month efficacy and safety data for Fabhalta in C3G from
the Phase II extension 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)(16-19).
"Our ambition is to transform the care of patients living with rare kidney
diseases by discovering, developing and delivering innovative treatment
options," said David Soergel, M.D., Global Head, Cardiovascular, Renal and
Metabolism Development Unit, Novartis. "The APPEAR-C3G results add to the
growing body of evidence demonstrating Fabhalta's potential to target the
underlying pathophysiological drivers and to provide clinically meaningful
outcomes in a range of rare conditions."
About APPEAR-C3G
APPEAR-C3G (NCT04817618) is a Phase III multicenter, randomized, double-blind,
parallel group, placebo-controlled study to evaluate the efficacy and safety of
twice-daily oral Fabhalta (200 mg) in C3G patients(2,3). In addition to the
results from adult patients with C3G, enrollment is ongoing in a separate cohort
of adolescent patients with C3G(2,3). The study comprises a 6-month double-blind
period where adult patients were randomized 1:1 to receive Fabhalta or placebo
on top of supportive care, followed by a 6-month open-label period where all
patients receive Fabhalta (including those who were previously on placebo)(
2,3).
The primary endpoint for the double-blind period was proteinuria reduction from
baseline at 6 months for Fabhalta compared to placebo as measured by 24-hour
UPCR(2,3). The primary endpoint for the open-label period is proteinuria
reduction from baseline at 12 months for both treatment arms and proteinuria
reduction from 6 to 12 months for the placebo arm(2,3). Secondary endpoints for
the double-blind period include change in eGFR, proportion of participants
meeting composite renal endpoint criteria (=50%
reduction in UPCR), change in glomerular inflammation (as measured by disease
total activity score in renal biopsy), change in patient reported fatigue (as
measured by FACIT-Fatigue score), and safety and tolerability(2,3).
About Fabhalta(®) (iptacopan)
Fabhalta (iptacopan) is an oral, Factor B inhibitor of the alternative
complement pathway(1).?
Discovered at Novartis, Fabhalta is currently in development for a range of rare
diseases including IgAN, C3G, aHUS, IC-MPGN and lupus nephritis (LN), and, as
such, the safety and efficacy profile have not been established in these
indications(2,11-13,20). There is no guarantee that Fabhalta will become
commercially available for these indications.
Fabhalta was approved by the FDA in December 2023 and the EMA in May 2024 for
the treatment of adults with the rare blood disorder paroxysmal nocturnal
hemoglobinuria (PNH) (21,22).
About C3 glomerulopathy (C3G)
C3G is an ultra-rare, progressive kidney disease that initially presents in
mostly children and young adults(4-6,23). Each year, approximately 1-2 people
per million worldwide are newly diagnosed with C3G, a form of
membranoproliferative glomerulonephritis (MPGN)(4).
In C3G, overactivation of the alternative complement pathway - part of the
immune system - causes deposits of C3 protein to build up in kidney glomeruli (a
network of blood vessels that filter waste and remove extra fluids from the
blood)(4,7,23-25). This triggers inflammation and glomerular damage that results
in proteinuria (protein in urine), hematuria (blood in urine) and reduced kidney
function(4,7,23-25). Approximately 50% of C3G patients progress to kidney
failure within 10 years of diagnosis, at which point they will require dialysis
and/or kidney transplantation(6,7), with over 55% of patients with
C3G experiencing disease recurrence post-transplant(26-29).
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, IC-MPGN and 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.
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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result of new information, future events or otherwise.
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