- Approval based on APPLY-PNH trial in adults with PNH and
anemia despite prior anti-C5 treatment, and supported by the
APPOINT-PNH study in complement inhibitor-naïve
patients1-5
- In APPLY-PNH, patients who switched to Fabhalta experienced
superior increases of hemoglobin levels ≥ 2 g/dL (82.3% vs. 0%) and
hemoglobin level ≥ 12 g/dL (67.7% vs. 0%), both in the absence of
red blood cell transfusions, vs. patients who continued on anti-C5
treatment1,2
- Fabhalta, now available for both previously treated
and treatment-naïve patients, is the only FDA-approved
Factor B inhibitor of the immune system's complement pathway, which
drives complement-mediated hemolysis in
PNH1,6
- Significant unmet need remains in PNH, a chronic and rare
blood disorder; despite anti-C5 therapy, a large proportion of
patients can remain anemic and dependent on blood
transfusions7,8
- Late-stage Fabhalta development program ongoing in multiple
complement-mediated conditions
EAST
HANOVER, N.J., Dec. 5, 2023
/PRNewswire/ -- Novartis today announced that the U.S. Food
and Drug Administration (FDA) approved Fabhalta®
(iptacopan) as the first oral monotherapy for the treatment of
adults with paroxysmal nocturnal hemoglobinuria (PNH)1.
Fabhalta is a Factor B inhibitor that acts proximally in the
alternative complement pathway of the immune system, providing
comprehensive control of red blood cell (RBC) destruction within
and outside the blood vessels (intra- and extravascular hemolysis
[IVH and EVH]). In clinical trials, treatment with Fabhalta
increased hemoglobin levels (≥ 2 g/dL from baseline in the absence
of RBC transfusions) in the majority of patients and in APPLY-PNH
nearly all patients treated with Fabhalta did not receive blood
transfusions1-5.
Experience the full interactive Multichannel News Release here:
https://www.multivu.com/players/English/9221051-novartis-fabhalta-fda-approval/
"An efficacious oral treatment with a demonstrated safety
profile could be practice-changing for physicians and help relieve
burdens experienced by people with PNH," said Vinod Pullarkat, MD, MRCP, Clinical Professor,
Department of Hematology and Hematopoietic Cell Transplantation,
City of Hope. "In clinical studies, iptacopan was superior to
anti-C5s in hemoglobin improvement in the absence of RBC
transfusion and transfusion avoidance rate, and also effective in
complement inhibitor-naïve individuals, by providing clinically
meaningful hemoglobin-level increases without the need for blood
transfusions."
The FDA approval is based on the Phase III APPLY-PNH trial in
patients with residual anemia (hemoglobin < 10 g/dL) despite
prior anti-C5 treatment who switched to Fabhalta, which
demonstrated superiority in hemoglobin improvement in the
absence of RBC transfusions and in transfusion avoidance rate over
patients who stayed on anti-C5 treatments1,2. Approval
was also supported by the Phase III APPOINT-PNH study in complement
inhibitor-naïve patients1,3. The 24-week core treatment
periods in APPLY-PNH and APPOINT-PNH trials respectively
showed1-3:
- Patients with sustained increase of hemoglobin levels ≥ 2
g/dLa from baseline in the absence of
transfusions: 82.3% of anti-C5-experienced
Fabhalta patients responded vs. 0% for anti-C5 (difference of
81.5%b, P<0.0001); 77.5% of complement
inhibitor-naïve patients using Fabhalta achieved this outcome
(sensitivity analysis showed 87.5%c)1-3.
- Patients with sustained hemoglobin level ≥ 12
g/dLa in the absence of transfusions: 67.7% of
anti-C5-experienced Fabhalta patients responded vs. 0% for anti-C5
(difference of 66.6%b, P<0.0001)1-2.
- Patients avoiding transfusiond,e: Transfusion
avoidance rate 95.2% for anti-C5-experienced Fabhalta patients vs.
45.7% for anti-C5 (difference of 49.5%b,
P<0.0001)1-2.
In the APPLY-PNH trial, the most commonly reported (≥10%)
adverse reactions (ARs) with Fabhalta vs. anti-C5s were:
headachef (19% vs. 3%), nasopharyngitisg (16%
vs. 17%), diarrhea (15% vs. 6%), abdominal painf (15%
vs. 3%), bacterial infectionh (11% vs. 11%), nausea (10%
vs. 3%), and viral infectioni (10% vs.
31%)1,2. In the APPOINT-PNH trial, the most commonly
reported ARs (≥10%) were headachef (28%), viral
infectioni (18%), nasopharyngitisg (15%), and
rashj (10%)1,3. In APPLY-PNH, serious ARs
were reported in two (3%) patients with PNH receiving Fabhalta,
which included pyelonephritis, urinary tract infection and
COVID-191,2. In APPOINT-PNH, serious ARs were reported
in two (5%) patients with PNH receiving Fabhalta, which included
COVID-19 and bacterial pneumonia1,3. Fabhalta may cause
serious infections caused by encapsulated bacteria and is available
only through a Risk Evaluation and Mitigation Strategy (REMS) that
requires vaccinations for encapsulated bacteria1.
People with PNH have an acquired mutation making red blood cells
susceptible to premature destruction by the complement
system6,8. PNH is characterized by hemolysis, bone
marrow failure, and thrombosis in varying combinations and levels
of severity6-8. Existing C5 inhibitor treatments,
administered as infusions, may leave PNH symptoms
uncontrolled7,8. Up to 88% of patients on anti-C5
treatment may have persistent anemia with over one-third of those
patients requiring blood transfusions at least once per
year7,8.
"The U.S. approval of Fabhalta is an extraordinary moment for
people living with PNH, their loved ones and the healthcare
providers who care for them," said Victor Bultó, President US,
Novartis. "This new, effective oral medicine may mean that patients
can reset their expectations of living with PNH, a chronic and
life-altering blood disease. As Novartis continues to focus on
conditions with unmet patient need, we are exploring the potential
of Fabhalta in other complement-mediated diseases – with an
ultimate goal to drive meaningful change for patients."
Discovered and developed by Novartis, Fabhalta is expected
to be available in the United
States in December. Additional regulatory filings and
reviews for Fabhalta in PNH are currently underway around the
world.
aAssessed between Day 126 and Day
168. bAdjusted difference in
proportion. cSensitivity analysis incorporates data from
local labs when central labs were not available.
dAssessed between Day 14 and Day 168.
eTransfusion avoidance is defined as absence of
administration of packed-red blood cell transfusions between Day 14
and Day 168. fIncludes similar terms.
gNasopharyngitis contains: rhinitis allergic, upper
respiratory tract infection, pharyngitis, rhinitis.
hBacterial infection contains: pyelonephritis, urinary
tract infection, bronchitis bacterial, bronchitis haemophilus,
cholecystitis, folliculitis, cellulitis, arthritis bacterial,
sepsis, klebsiella infection, staphylococcal infection, Pseudomonas
infection, hordeolum, pneumonia bacterial. iViral
infection contains: COVID-19, herpes zoster, oral herpes, nasal
herpes, influenza A virus test positive, influenza.
jRash: dermatitis allergic, acne, erythema multiforme,
rash maculo-papular, rash erythematous.
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 and
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 randomization2,10. 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)2,9.
About APPOINT-PNH
APPOINT-PNH (NCT04820530) was a Phase III, multinational,
multicenter, open-label, uncontrolled single-arm study to evaluate
the efficacy and safety of twice-daily, oral Fabhalta monotherapy
(200 mg) in adult PNH patients who are naïve to complement
inhibitor therapy, including anti-C5 therapies (eculizumab or
ravulizumab)3,10.The trial enrolled 40 patients who
received twice-daily, oral Fabhalta
monotherapy3,10.
About paroxysmal nocturnal hemoglobinuria (PNH)
PNH is a rare, chronic and serious complement-mediated blood
disorder6. 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
system6,8. 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) and other debilitating
symptoms6,8.
It is estimated that approximately 10-20 people per million
worldwide live with PNH6. Although PNH can develop at
any age, it is often diagnosed in people between 30-40 years
old11,12.
PNH has a significant unmet need not fully addressed by anti-C5
therapies (eculizumab or ravulizumab): despite treatment with
anti-C5s, a large proportion of people with PNH may remain anemic,
and dependent on blood transfusions6-8,13,14.
About Fabhalta® (iptacopan)
Fabhalta
(iptacopan) is an oral, Factor B inhibitor of the alternative
complement pathway15-17. Fabhalta is indicated 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 Breakthrough Therapy Designation
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 IgAN18-21.
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 FABHALTA (iptacopan). 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 FABHALTA (iptacopan)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 and
https://www.novartis.us and connect with us on
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