- APPLY-PNH extension data show that continuous
Fabhalta® (iptacopan) treatment in adults with
paroxysmal nocturnal hemoglobinuria (PNH) enabled sustained
hemoglobin-level increases to near-normal (≥12 g/dL), blood
transfusion avoidance, and improved patient-reported fatigue in the
majority of patients, with a safety profile consistent with
previously reported data1-5
- Patients switching from anti-C5s to Fabhalta in the
extension period achieved outcomes comparable to the Fabhalta arm
in the 24-week randomized controlled period, including transfusion
avoidance and near-normal hemoglobin-levels (≥12 g/dL) in the
majority of patients1
- Fabhalta was recently approved by the FDA for adults
with PNH, including for both previously treated and
treatment-naive patients6
EAST
HANOVER, N.J., Dec. 10,
2023 /PRNewswire/ -- Novartis today announced results
from the extension period of the pivotal Phase III APPLY-PNH trial
of oral monotherapy Fabhalta® (iptacopan) in adults with
paroxysmal nocturnal hemoglobinuria (PNH) who had residual anemia
(hemoglobin <10 g/dL) despite previous anti-C5
therapy1,2. Continuous Fabhalta treatment (200 mg twice
daily) for 48 weeks enabled sustained hemoglobin-level increases to
near-normal (12 g/dL or more), blood transfusion avoidance, and
reduced patient-reported fatigue in the majority of patients;
comparable benefits emerged in those patients switching from
anti-C5 therapy to Fabhalta in the extension1. Data will
be presented at the 65th American Society of Hematology
Annual Meeting & Exposition (ASH).
"The new APPLY-PNH data are an expansion of the robust outcomes
we saw in the randomized phase and demonstrate that patients with
PNH who took Fabhalta experienced meaningful hemoglobin improvement
over the longer term – nearly a year," said principal
co-investigator Antonio Risitano,
M.D., Ph.D., President of the International PNH Interest Group and
Head of the Hematology and Hematopoietic Transplant Unit, Reference
Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria
at the AORN San Giuseppe Moscati, Avellino, Italy. "Additionally, the new data confirm
that these benefits may occur within weeks after switching from
anti-C5s. The APPLY-PNH findings continue to confirm Fabhalta as a
promising therapeutic option for people living with
PNH."
Patients completing the 24-week randomized treatment period of
APPLY-PNH could elect to enter the extension, continuing Fabhalta
(61/62 patients; one patient discontinued due to pregnancy) or
switching from anti-C5s to Fabhalta (34/35 patients; one patient
discontinued based on investigator decision) through week
481,2.
In the continuous Fabhalta group, outcomes achieved in the
randomized period were sustained at 48 weeks: mean hemoglobin level
continued to be near-normal (12.2 g/dL), nearly all patients
(91.9%) remained free of transfusions (Weeks 2-48), and
improvements in patient-reported fatigue were observed (adjusted
mean change from baseline: 9.80-point increase in Functional
Assessment of Chronic Illness Therapy – Fatigue [FACIT-F]
score)1.
In the anti-C5-to-Fabhalta group, similar benefits emerged after
switch: mean hemoglobin levels increased to near-normal (from 9.1
g/dL at 24 weeks to 12.1 g/dL at 48 weeks), transfusion avoidance
was achieved for almost all patients (94.1%, Weeks 26-48), and
improvements in patient-reported fatigue were observed after
switching to Fabhalta (adjusted mean change from baseline between
Week 48 and Week 24: 10.79-point increase in FACIT-F
score)1.
"Coming on the heels of Fabhalta's recent approval in PNH, these
extended data from the APPLY-PNH phase III trial reinforce
Fabhalta's utility as an important new oral monotherapy for people
living with PNH," said David
Soergel, M.D., Global Head, Cardiovascular, Renal and
Metabolism Development Unit, Novartis. "We are eager to bring this
novel treatment to even more people living with rare
complement-driven disorders as we pursue several additional
indications for Fabhalta."
Fabhalta had a similar safety profile at 48 weeks vs. 24
weeks1,2. Three patients had major adverse vascular
events (MAVEs), all considered unrelated to Fabhalta (one serious
transient ischemic attack [TIA] occurred in the randomized period
and was reported previously)1,2. In the extension, there
was one non-serious TIA and one serious portal vein thrombosis
(PVT; this patient had a history of PVT and discontinued heparin
prior to the MAVE)1. Six patients of 62 receiving
continuous Fabhalta for 48 weeks had clinical breakthrough
hemolysis (BTH); one patient in the anti-C5-to-Fabhalta extension
arm had clinical BTH after switching (compared to six of 35
patients while on anti-C5s prior to switch)1,2. All
cases of clinical BTH resolved without changing Fabhalta
dosing1. During the 48-week study period, the most
frequently reported treatment-emergent adverse events (TEAEs) in
the Fabhalta arm were COVID-19 (29.0% of patients), headache
(19.4%), and diarrhea (16.1%)1. Throughout the full 48
weeks on Fabhalta, 9.7% of patients experienced any severe TEAE,
and 14.5% experienced any serious TEAE, none of which was suspected
to be related to Fabhalta treatment; there were no serious
hemolysis TEAEs on Fabhalta1,2. There were no serious
infections caused by N. meningitidis, S. pneumoniae, or
H. influenzae and no treatment discontinuations because of
TEAEs1,2.
PNH is a rare, chronic, and serious complement-mediated blood
disorder in which a large proportion of patients can remain anemic
and some dependent on blood transfusions despite currently
available standard of care, anti-C5
treatments7-10.
Full 48-week results from the Phase III APPOINT-PNH trial in
treatment-naïve PNH patients will be presented at a congress in
2024.
Indication
FABHALTA is a prescription medicine used to
treat adults with paroxysmal nocturnal hemoglobinuria (PNH).
It is not known if FABHALTA is safe and effective in
children.
Important Safety Information
FABHALTA is a medicine
that affects part of the immune system and may lower one's ability
to fight infections. FABHALTA increases the chance of getting
serious infections caused by encapsulated bacteria, including
Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus
influenzae type B. These serious infections may quickly become
life-threatening or fatal if not recognized and treated early.
Patients must complete or update vaccinations against these
bacteria at least 2 weeks before starting FABHALTA. If patients
have not completed these vaccinations and FABHALTA therapy must be
started right away, they should receive the required vaccinations
as soon as possible. If patients have not been vaccinated and
FABHALTA must be started right away, they should also receive
antibiotics to take for as long as their doctor tells them. If
patients have been vaccinated against these bacteria in the past,
they might need additional vaccinations before starting FABHALTA.
Their doctor will decide if they need additional vaccinations.
Vaccines do not prevent all infections caused by encapsulated
bacteria. Patients should call their doctor or get emergency
medical care right away if they have any of these signs and
symptoms of a serious infection: fever with or without shivers or
chills; fever with chest pain and cough; fever with high heart
rate; headache and fever; confusion; clammy skin; fever and a rash;
fever with breathlessness/fast breathing; headache with nausea or
vomiting; headache with stiff neck or stiff back; body aches with
flu-like symptoms; or eyes sensitive to light. Doctors will give
their patients a Patient Safety Card about the risk of serious
infections. Patients must carry it with them at all times during
treatment and for 2 weeks after their last dose of FABHALTA. The
risk of serious infections may continue for a few weeks after their
last dose of FABHALTA. It is important for patients to show this
card to any doctor who treats them. This will help doctors diagnose
and treat patients quickly.
FABHALTA is only available through a program called the FABHALTA
Risk Evaluation and Mitigation Strategy (REMS). Before patients can
take FABHALTA, their doctor must enroll in the FABHALTA REMS
program, counsel patients about the risk of serious infections
caused by certain bacteria, give patients information about the
symptoms of serious infections, make sure that patients are
vaccinated against serious infections caused by encapsulated
bacteria and that they receive antibiotics if they need to start
FABHALTA right away and are not up to date on vaccinations, as well
as give patients a Patient Safety Card about the risk of serious
infections.
Since FABHALTA may increase patients' cholesterol and
triglycerides, their doctor will do blood tests to check their
levels periodically.
Patients should not take FABHALTA if they are allergic to
FABHALTA or any of the ingredients in FABHALTA. Patients should not
take FABHALTA if they have a serious infection caused by
encapsulated bacteria, including Streptococcus pneumoniae,
Neisseria meningitidis, or Haemophilus influenzae type B when
starting FABHALTA.
Before taking FABHALTA, patients should tell their doctor about
all their medical conditions, including if they have an infection
or fever, have kidney or liver problems, are pregnant or plan to
become pregnant (it is not known if FABHALTA will harm an unborn
baby), or are breastfeeding or plan to breastfeed as it is not
known if FABHALTA passes into breast milk. Patients should not
breastfeed during treatment and for 5 days after the last dose of
FABHALTA.
Patients should tell their doctor about all the medicines they
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements. Taking FABHALTA with certain
other medicines may affect the way FABHALTA works and may cause
side effects. Patients should know the medicines they take and the
vaccines they receive. Patients should keep a list of them to show
their doctor and pharmacist when they get a new medicine.
If patients have PNH and stop taking FABHALTA, their doctor will
need to monitor them closely for at least 2 weeks after stopping
FABHALTA. Stopping treatment with FABHALTA may cause a breakdown of
red blood cells due to PNH. Symptoms or problems that can happen
due to breakdown of red blood cells include decreased hemoglobin
level in the blood; blood in the urine; shortness of breath;
trouble swallowing; tiredness; pain in the stomach (abdomen); blood
clots, stroke, and heart attack; and erectile dysfunction (ED). It
is important that patients take FABHALTA exactly as their doctor
tells them to lower the possibility of breakdown of red blood cells
due to PNH.
The most common side effects of FABHALTA include headache; nasal
congestion, runny nose, cough, sneezing, and sore throat
(nasopharyngitis); diarrhea; pain in the stomach (abdomen);
infections (viral and bacterial); nausea; and rash.
Please see full Prescribing Information, including Boxed
WARNING and Medication Guide.
About APPLY-PNH
APPLY-PNH (NCT04558918) was a Phase III, randomized, multinational,
multicenter, active-comparator controlled, open-label trial to
evaluate the efficacy and safety of twice-daily, oral Fabhalta
monotherapy (200 mg) for the treatment of PNH by assessing if
switching to Fabhalta was superior to continuing on anti-C5
therapies (US-approved and non-US-approved eculizumab or
ravulizumab) in adult patients presenting with residual anemia (Hb
<10 g/dL) despite a stable regimen of anti-C5 treatment in the
last six months prior to randomization4,11. The trial
enrolled 97 patients who were randomized in an 8:5 ratio to either
twice-daily, oral Fabhalta monotherapy, or intravenous anti-C5
therapies (continuing with the same regimen as they were on prior
to randomization)4,11.
About paroxysmal nocturnal hemoglobinuria (PNH)
PNH is a rare, chronic and serious complement-mediated blood
disorder7. People with PNH have an acquired mutation in
some of their hematopoietic stem cells (which are located in the
bone marrow and can grow and develop into RBCs, white blood cells
and platelets) that causes them to produce RBCs that are
susceptible to premature destruction by the complement
system7,8. This leads to intravascular hemolysis
(destruction of RBCs within blood vessels) and extravascular
hemolysis (destruction of RBCs mostly in the spleen and liver),
which cause anemia (low levels of circulating RBCs), thrombosis
(formation of blood clots), fatigue and other debilitating
symptoms7,8.
It is estimated that approximately 10-20 people per million
worldwide live with PNH7. Although PNH can develop at
any age, it is often diagnosed in people between 30-40 years
old12-14.
PNH has a significant unmet need not addressed by anti-C5
therapies (eculizumab or ravulizumab): despite treatment with
anti-C5s, a large proportion of people with PNH remain anemic, and
some dependent on blood
transfusions7-10,15.
About Fabhalta® (iptacopan)
Fabhalta (iptacopan) is an oral, Factor B inhibitor of the
alternative complement pathway14,16,17. Fabhalta is
FDA-approved for the treatment of adults with paroxysmal nocturnal
hemoglobinuria (PNH).
Discovered at Novartis, Fabhalta is currently in
development for a range of complement-mediated diseases including,
immunoglobulin A nephropathy (IgA nephropathy), C3 glomerulopathy
(C3G), immune complex membranoproliferative glomerulonephritis
(IC-MPGN) and atypical hemolytic uremic syndrome
(aHUS).
Based on disease prevalence, unmet needs and data from Phase II
studies, Fabhalta has received FDA approval in PNH, FDA
Breakthrough Therapy Designation in C3G, orphan drug designations
from the FDA and EMA in PNH and C3G, EMA
PRIME designation for C3G, and EMA orphan drug designation
in IgAN6,18-22.
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,"
"expectations," "investigational," "drives," "remains," "ongoing,"
"exploring," "goal," "expected," "estimated," or similar terms, or
by express or implied discussions regarding potential marketing
approvals, new indications or labeling for FABHALTA (iptacopan), 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 FABHALTA (iptacopan) 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
future. In particular, our expectations regarding FABHALTA
(iptacopan) 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; regulatory actions or delays or government regulation
generally; global trends toward health care cost containment,
including government, payor and general public pricing and
reimbursement pressures and requirements for increased pricing
transparency; our ability to obtain or maintain proprietary
intellectual property protection; the particular prescribing
preferences of physicians and patients; general political, economic
and business conditions, including the effects of and efforts to
mitigate pandemic diseases; safety, quality, data integrity or
manufacturing issues; potential or actual data security and data
privacy breaches, or disruptions of our information technology
systems, and other risks and factors referred to in Novartis AG's
current Form 20-F on file with the US Securities and Exchange
Commission. Novartis is providing the information in this press
release as of this date and does not undertake any obligation to
update any forward-looking statements contained in this press
release as a result of new information, future events or
otherwise.
About Novartis
Novartis is an innovative
medicines company. Every day, we work to reimagine medicine to
improve and extend people's lives so that patients, healthcare
professionals and societies are empowered in the face of serious
disease. Our medicines reach more than 250 million people
worldwide.
Reimagine medicine with us: Visit us
at https://www.novartis.com
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