Data demonstrated effective control of
intravascular and extravascular hemolysis through 48 weeks
Results showed increase in mean hemoglobin
levels were maintained through 48 weeks
Positive results from the 24-week and long-term extension (LTE)
period of the pivotal ALPHA Phase III trial showed danicopan as
add-on to standard of care C5 inhibitor therapy ULTOMIRIS®
(ravulizumab-cwvz) or SOLIRIS® (eculizumab) continued to
demonstrate clinical benefit for patients with paroxysmal nocturnal
hemoglobinuria (PNH) who experience clinically significant
extravascular hemolysis (EVH).1
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Hemoglobin levels improved with danicopan
at 12 weeks and were maintained through 48 weeks. (Photo: Business
Wire)
Results from the trial were presented today at the 65th American
Society of Hematology (ASH) Annual Meeting and Exposition in San
Diego, California. Danicopan is an investigational, first-in-class,
oral, Factor D inhibitor.
Data showed that improvements in mean hemoglobin levels and
absolute reticulocyte count (ARC) levels, which were demonstrated
at 12 weeks, were maintained through 48 weeks.1
PNH is a rare and severe blood disorder characterized by the
destruction of red blood cells within blood vessels, known as
intravascular hemolysis (IVH), and white blood cell and platelet
activation that can cause thrombosis (blood clots) and result in
organ damage and potentially premature death.2-4 Immediate,
complete and sustained terminal complement inhibition by blocking
the C5 protein with ULTOMIRIS or SOLIRIS helps reduce symptoms and
complications, resulting in improved survival for patients with
PNH.4-7 Approximately 10-20% of people living with PNH who are
treated with a C5 inhibitor experience clinically significant EVH,
which can result in continued symptoms of anemia and require blood
transfusions.2,8-12
Austin Kulasekararaj, MD, Consultant Hematologist at King's
College Hospital, London and investigator in the ALPHA trial, said:
“These new data further demonstrate the potential of danicopan as
add-on to ULTOMIRIS or SOLIRIS to address the needs of the small
subset of patients with PNH who experience clinically significant
EVH. Expanding on positive 12-week results, the findings
demonstrate sustained improvements in hemoglobin levels for up to
48 weeks, while also maintaining disease control, as measured by
lactate dehydrogenase levels.”
Gianluca Pirozzi, Senior Vice President, Head of Development,
Regulatory and Safety, Alexion, said: “Unlike IVH, EVH is not
life-threatening, but its manifestations can be burdensome for
people living with this condition, which is why we continue to
explore the potential of the complement system to advance patient
care. The pivotal ALPHA results suggest that dual complement
pathway inhibition at Factor D and C5 may be an optimal treatment
approach for the 10-20% of patients with PNH who experience
clinically significant EVH. Importantly, C5 inhibition maintains
effective IVH control, which is critical for patients, and the
addition of Factor D inhibition addresses signs and symptoms of
EVH.”
The pivotal ALPHA Phase III trial is designed as a superiority
study to evaluate the efficacy and safety of danicopan as an add-on
to C5 inhibitor therapy ULTOMIRIS or SOLIRIS in patients with PNH
who experience clinically significant EVH. A total of 86 patients
were randomized. The prespecified interim analysis (primary
analysis) occurred after 63 participants either completed or
discontinued from the primary treatment period of 12 weeks.
Following the 12-week randomized control period, patients were
eligible to enroll in an open-label treatment period for an
additional 12 weeks. During the open-label period, participants
receiving placebo plus ULTOMIRIS or SOLIRIS switched to danicopan
plus ULTOMIRIS or SOLIRIS (placebo-danicopan), and participants
receiving add-on therapy with danicopan continued treatment with
danicopan add-on therapy (danicopan-danicopan). The open-label
treatment period was followed by the option to join a two-year LTE
period during which all participants received danicopan add-on
therapy. At the time of data cut-off on September 20, 2022, 60 of
the 63 patients who were included in the primary analysis had
reached 24 weeks and entered the LTE.1
Data showed that the significant improvements in hemoglobin
levels observed at 12 weeks [LSM (SEM) change 2.94 (0.21) g/dL]
continued at 24 weeks [LSM (SEM) change 3.17 (0.30) g/dL] among
patients treated with danicopan plus ULTOMIRIS or SOLIRIS and were
sustained through 48 weeks.1
Secondary endpoints measured at 24 weeks include change from
baseline in hemoglobin, ARC, and lactate dehydrogenase (LDH)
levels; the percentage of patients with hemoglobin increase of ≥2
g/dL in the absence of transfusion; and the percentage of patients
with transfusion avoidance.1
All key secondary endpoints met superiority in favor of
danicopan plus ULTOMIRIS or SOLIRIS compared to placebo plus
ULTOMIRIS or SOLIRIS at 12 weeks, and data showed benefits were
maintained at 24 weeks in the danicopan-danicopan arm.1
Further, all key secondary endpoints showed meaningful
improvement at 24 weeks in patients who switched from placebo to
add-on treatment with danicopan at 12 weeks, including ARC levels
and percentage of patients with transfusion avoidance, two
indicators of potential EVH.1
Additionally, mean (SD) LDH levels were maintained from baseline
through 48 weeks in both treatment arms, demonstrating effective
control of terminal complement activity and IVH with ULTOMIRIS or
SOLIRIS.1
Summary of efficacy resultsi
Hemoglobin and ARC levels improved with danicopan at 12 weeks
and were maintained through 48 weeks (please see hemoglobin and ARC
level graphs included in the image carousel).
Endpoints
Statistic
Danicopan-Danicopan
Placebo-Danicopan
Change at 12
weeks
Change at 24
weeks
Change at 12
weeks
Change at 24 weeks
Change from baseline in hemoglobin
(g/dL)
LSM (SEM)
2.94 (0.21)
3.17 (0.30)
0.50 (0.31)
2.26 (0.34)
Change from baseline in ARC levels
(×109/L)
LSM (SEM)
–83.8 (8.93)
–80.2 (8.75)
3.5 (12.68)
–65.2 (12.74)
Change from baseline in LDH levels
(U/L)
LSM (SEM)
–23.49 (8.29)
–17.79 (13.73)
–2.92 (11.91)
–6.03 (18.77)
Endpoints
Statistic
Danicopan-Danicopan
Placebo-Danicopan
Percent at 12
weeks
Percent at 24
weeks
Percent at 12
weeks
Percent at 24 weeks
Proportion of participants with
transfusion avoidance (%)
Percent (%)
83
78
38
90
i. LDH, lactate dehydrogenase; ARC, absolute reticulocyte count;
LSM, least squares mean; SEM, standard error of the mean; ULN,
upper limit of normal.
Results from the ALPHA Phase III trial and LTE showed danicopan
is generally well tolerated, and no new safety concerns were
identified. The safety analysis was performed using data from all
participants who took at least one dose of danicopan (n=80). The
most common treatment-emergent adverse events (TEAEs) (≥10%) were
COVID-19 (21.3%), diarrhea (15%), headache (15%), pyrexia (13.8%),
nausea (12.5%) and fatigue (10%).1
Additionally, an analysis of patient-reported outcomes from the
ALPHA Phase III trial at 24 weeks was also presented at ASH,
suggesting danicopan plus ULTOMIRIS or SOLIRIS has the potential to
improve quality of life compared to C5 inhibitor therapy alone for
the 10-20% of patients with PNH who experience clinically
significant EVH.13 Findings showed clinically relevant
patient-reported outcomes were observed in patients treated with
danicopan as add-on to ULTOMIRIS or SOLIRIS during the first 12
weeks of treatment, compared to placebo plus C5 inhibition.
Additionally, data showed improvements in Functional Assessment of
Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and European
Organization for Research and Treatment of Cancer Quality of Life
Questionnaire-Core 30 Scale (EORTC-QLQ-C30) scores were maintained
during the open-label period to 24 weeks in the danicopan-danicopan
arm and improved at 24 weeks in the placebo-danicopan arm.13
ALPHA Phase III trial results from the primary prespecified
interim analysis at 12 weeks were presented at the European
Hematology Association (EHA) 2023 Hybrid Congress and published in
The Lancet Haematology.
Regulatory submissions for danicopan are currently under review
with multiple global health authorities.
INDICATION(S) & IMPORTANT SAFETY INFORMATION for
ULTOMIRIS® (ravulizumab-cwvz)
What is ULTOMIRIS?
ULTOMIRIS is a prescription medicine used to treat:
- adults and children 1 month of age and older with a disease
called Paroxysmal Nocturnal Hemoglobinuria (PNH).
- adults and children 1 month of age and older with a disease
called atypical Hemolytic Uremic Syndrome (aHUS). ULTOMIRIS is not
used in treating people with Shiga toxin E. coli related hemolytic
uremic syndrome (STEC-HUS).
- adults with a disease called generalized Myasthenia Gravis
(gMG) who are anti-acetylcholine receptor (AChR) antibody
positive.
- adults with PNH or aHUS when administered subcutaneously (under
your skin).
It is not known if ULTOMIRIS is safe and effective in children
younger than 1 month of age.
It is not known if ULTOMIRIS is safe and effective for the
treatment of gMG in children.
Subcutaneous administration of ULTOMIRIS has not been evaluated
and is not approved for use in children.
IMPORTANT SAFETY INFORMATION
What is the most important information I should know about
ULTOMIRIS?
ULTOMIRIS is a medicine that affects your immune system and
can lower the ability of your immune system to fight
infections.
- ULTOMIRIS increases your chance of getting serious and
life-threatening meningococcal infections that may quickly become
life-threatening and cause death if not recognized and treated
early.
- You must receive meningococcal vaccines at least 2 weeks before
your first dose of ULTOMIRIS if you are not vaccinated.
- If your healthcare provider decided that urgent treatment with
ULTOMIRIS is needed, you should receive meningococcal vaccination
as soon as possible.
- If you have not been vaccinated and ULTOMIRIS therapy must be
initiated immediately, you should also receive 2 weeks of
antibiotics with your vaccinations.
- If you had a meningococcal vaccine in the past, you might need
additional vaccination. Your healthcare provider will decide if you
need additional vaccination.
- Meningococcal vaccines reduce but do not prevent all
meningococcal infections. Call your healthcare provider or get
emergency medical care right away if you get any of these signs and
symptoms of a meningococcal infection: headache with nausea or
vomiting, headache and fever, headache with a stiff neck or stiff
back, fever, fever and a rash, confusion, muscle aches with
flu-like symptoms and eyes sensitive to light.
Your healthcare provider will give you a Patient Safety Card
about the risk of meningococcal infection. Carry it with you at
all times during treatment and for 8 months after your last
ULTOMIRIS dose. It is important to show this card to any healthcare
provider or nurse to help them diagnose and treat you quickly.
ULTOMIRIS is only available through a program called the
ULTOMIRIS REMS. Before you can receive ULTOMIRIS, your
healthcare provider must: enroll in the ULTOMIRIS REMS program;
counsel you about the risk of meningococcal infection; give you
information and a Patient Safety Card about the symptoms and your
risk of meningococcal infection (as discussed above); and make sure
that you are vaccinated with a meningococcal vaccine, and if
needed, get revaccinated with the meningococcal vaccine. Ask your
healthcare provider if you are not sure if you need to be
revaccinated.
ULTOMIRIS may also increase the risk of other types of
serious infections. Make sure your child receives vaccinations
against Streptococcus pneumoniae and Haemophilus influenzae type b
(Hib) if treated with ULTOMIRIS. Call your healthcare provider
right away if you have any new signs or symptoms of infection.
Who should not receive ULTOMIRIS?
Do not receive ULTOMIRIS if you have a meningococcal
infection or have not been vaccinated against meningococcal
infection unless your healthcare provider decides that urgent
treatment with ULTOMIRIS is needed.
Before you receive ULTOMIRIS, tell your healthcare provider
about all of your medical conditions, including if you: have an
infection or fever, are pregnant or plan to become pregnant, and
are breastfeeding or plan to breastfeed. It is not known if
ULTOMIRIS will harm your unborn baby or if it passes into your
breast milk. You should not breastfeed during treatment and for 8
months after your final dose of ULTOMIRIS.
Tell your healthcare provider about all the vaccines you
receive and medicines you take, including prescription and
over-the-counter medicines, vitamins, and herbal supplements which
could affect your treatment.
If you have PNH and you stop receiving ULTOMIRIS, your
healthcare provider will need to monitor you closely for at least
16 weeks after you stop ULTOMIRIS. Stopping ULTOMIRIS may cause
breakdown of your red blood cells due to PNH. Symptoms or problems
that can happen due to red blood cell breakdown include: drop
in your red blood cell count, tiredness, blood in your urine,
stomach-area (abdomen) pain, shortness of breath, blood clots,
trouble swallowing, and erectile dysfunction (ED) in males.
If you have aHUS, your healthcare provider will need to
monitor you closely for at least 12 months after stopping treatment
for signs of worsening aHUS or problems related to a type of
abnormal clotting and breakdown of your red blood cells called
thrombotic microangiopathy (TMA). Symptoms or problems that can
happen with TMA may include: confusion or loss of
consciousness, seizures, chest pain (angina), difficulty breathing
and blood clots or stroke.
ULTOMIRIS can cause serious side effects including allergic
reactions to acrylic adhesive. Allergic reactions to the
acrylic adhesive may happen with your subcutaneous ULTOMIRIS
treatment. If you have an allergic reaction during the delivery of
subcutaneous ULTOMIRIS, remove the on-body injector and get medical
help right away. Your healthcare provider may treat you with
medicines to help prevent or treat allergic reaction symptoms as
needed.
What are the possible side effects of ULTOMIRIS?
ULTOMIRIS can cause serious side effects including
infusion-related reactions. Symptoms of an infusion-related
reaction with ULTOMIRIS may include lower back pain, tiredness,
feeling faint, discomfort in your arms or legs, bad taste, or
drowsiness. Stop treatment of ULTOMIRIS and tell your healthcare
provider or nurse right away if you develop these symptoms, or any
other symptoms during your ULTOMIRIS infusion that may mean you are
having a serious infusion reaction, including: chest pain, trouble
breathing or shortness of breath, swelling of your face, tongue, or
throat, and feel faint or pass out.
The most common side effects of ULTOMIRIS in people treated
for PNH are upper respiratory tract infection and headache.
The most common side effects of ULTOMIRIS in people treated
for aHUS are upper respiratory tract infection, diarrhea, nausea,
vomiting, headache, high blood pressure and fever.
The most common side effects of ULTOMIRIS in people with gMG
are diarrhea and upper respiratory tract infections.
The most common side effects of subcutaneous administration
of ULTOMIRIS in adults treated for PNH and aHUS are local injection
site reactions.
Tell your healthcare provider about any side effect that bothers
you or that does not go away. These are not all the possible side
effects of ULTOMIRIS. For more information, ask your healthcare
provider or pharmacist. Call your healthcare provider right away if
you miss an ULTOMIRIS infusion or for medical advice about side
effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the Instructions for Use that comes with subcutaneous
ULTOMIRIS for instructions about the right way to prepare and give
your subcutaneous ULTOMIRIS injections through an on-body
injector.
Please see the accompanying full Prescribing
Information and Medication Guide for
ULTOMIRIS, including Boxed WARNING regarding serious and
life-threatening meningococcal infections/sepsis. Please see the
accompanying Instructions for Use for the ULTOMIRIS On Body
Delivery System.
INDICATIONS & IMPORTANT SAFETY INFORMATION FOR SOLIRIS®
(eculizumab) [injection for intravenous use 300mg/30mL
vial]
What is SOLIRIS?
SOLIRIS is a prescription medicine used to treat:
- patients with a disease called Paroxysmal Nocturnal
Hemoglobinuria (PNH).
- adults and children with a disease called atypical Hemolytic
Uremic Syndrome (aHUS). SOLIRIS is not for use in treating people
with Shiga toxin E. coli related hemolytic uremic syndrome
(STEC-HUS).
- adults with a disease called generalized myasthenia gravis
(gMG) who are anti-acetylcholine receptor (AChR) antibody
positive.
- adults with a disease called neuromyelitis optica spectrum
disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody
positive.
It is not known if SOLIRIS is safe and effective in children
with PNH, gMG, or NMOSD.
IMPORTANT SAFETY INFORMATION
What is the most important information I should know about
SOLIRIS?
SOLIRIS is a medicine that affects your immune system and can
lower the ability of your immune system to fight
infections.
- SOLIRIS increases your chance of getting serious and
life-threatening meningococcal infections that may quickly become
life-threatening and cause death if not recognized and treated
early.
- You must receive meningococcal vaccines at least 2 weeks before
your first dose of SOLIRIS if you are not vaccinated.
- If your doctor decided that urgent treatment with SOLIRIS is
needed, you should receive meningococcal vaccination as soon as
possible.
- If you have not been vaccinated and SOLIRIS therapy must be
initiated immediately, you should also receive 2 weeks of
antibiotics with your vaccinations.
- If you had a meningococcal vaccine in the past, you might need
additional vaccination. Your doctor will decide if you need
additional vaccination.
- Meningococcal vaccines reduce but do not prevent all
meningococcal infections. Call your doctor or get emergency medical
care right away if you get any of these signs and symptoms of a
meningococcal infection: headache with nausea or vomiting, headache
and fever, headache with a stiff neck or stiff back, fever, fever
and a rash, confusion, muscle aches with flu-like symptoms, and
eyes sensitive to light.
Your doctor will give you a Patient Safety Card about the
risk of meningococcal infection. Carry it with you at all times
during treatment and for 3 months after your last SOLIRIS dose. It
is important to show this card to any doctor or nurse to help them
diagnose and treat you quickly.
SOLIRIS is only available through a program called the
SOLIRIS REMS. Before you can receive SOLIRIS, your doctor must
enroll in the SOLIRIS REMS program; counsel you about the risk of
meningococcal infection; give you information and a Patient
Safety Card about the symptoms and your risk of meningococcal
infection (as discussed above); and make sure that you are
vaccinated with the meningococcal vaccine and, if needed, get
revaccinated with the meningococcal vaccine. Ask your doctor if you
are not sure if you need to be revaccinated.
SOLIRIS may also increase the risk of other types of serious
infections. Make sure your child receives vaccinations against
Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) if
treated with SOLIRIS. Certain people may be at risk of serious
infections with gonorrhea. Certain fungal infections (Aspergillus)
may occur if you take SOLIRIS and have a weak immune system or a
low white blood cell count.
Who should not receive SOLIRIS?
Do not receive SOLIRIS if you have a meningococcal infection
or have not been vaccinated against meningitis infection unless
your doctor decides that urgent treatment with SOLIRIS is
needed.
Before you receive SOLIRIS, tell your doctor about all of
your medical conditions, including if you: have an infection or
fever, are pregnant or plan to become pregnant, and are
breastfeeding or plan to breastfeed. It is not known if SOLIRIS
will harm your unborn baby or if it passes into your breast
milk.
Tell your doctor about all the vaccines you receive and
medicines you take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements which could affect your
treatment. It is important that you have all recommended
vaccinations before you start SOLIRIS, receive 2 weeks of
antibiotics if you immediately start SOLIRIS, and stay up-to-date
with all recommended vaccinations during treatment with
SOLIRIS.
If you have PNH, your doctor will need to monitor you closely
for at least 8 weeks after stopping SOLIRIS. Stopping treatment
with SOLIRIS may cause breakdown of your red blood cells due to
PNH. Symptoms or problems that can happen due to red blood cell
breakdown include: drop in the number of your red blood cell count,
drop in your platelet count, confusion, kidney problems, blood
clots, difficulty breathing, and chest pain.
If you have aHUS, your doctor will need to monitor you
closely during and for at least 12 weeks after stopping treatment
for signs of worsening aHUS symptoms or problems related to
abnormal clotting (thrombotic microangiopathy). Symptoms or
problems that can happen with abnormal clotting may include:
stroke, confusion, seizure, chest pain (angina), difficulty
breathing, kidney problems, swelling in arms or legs, and a drop in
your platelet count.
What are the possible side effects of SOLIRIS?
SOLIRIS can cause serious side effects including serious
infusion-related reactions. Tell your doctor or nurse right
away if you get any of these symptoms during your SOLIRIS infusion:
chest pain; trouble breathing or shortness of breath; swelling of
your face, tongue, or throat; and feel faint or pass out. If you
have an infusion-related reaction to SOLIRIS, your doctor may need
to infuse SOLIRIS more slowly, or stop SOLIRIS.
The most common side effects in people with PNH treated with
SOLIRIS include: headache, pain or swelling of your nose or
throat (nasopharyngitis), back pain, and nausea.
The most common side effects in people with aHUS treated with
SOLIRIS include: headache, diarrhea, high blood pressure
(hypertension), common cold (upper respiratory infection),
stomach-area (abdominal) pain, vomiting, pain or swelling of your
nose or throat (nasopharyngitis), low red blood cell count
(anemia), cough, swelling of legs or feet (peripheral edema),
nausea, urinary tract infections, and fever.
The most common side effects in people with gMG treated with
SOLIRIS include: muscle and joint (musculoskeletal) pain.
The most common side effects in people with NMOSD treated
with SOLIRIS include: common cold (upper respiratory
infection); pain or swelling of your nose or throat
(nasopharyngitis); diarrhea; back pain; dizziness; flu-like
symptoms (influenza), including fever, headache, tiredness, cough,
sore throat, and body aches; joint pain (arthralgia); throat
irritation (pharyngitis); and bruising (contusion).
Tell your doctor about any side effect that bothers you or that
does not go away. These are not all the possible side effects of
SOLIRIS. For more information, ask your doctor or pharmacist. Call
your doctor for medical advice about side effects. You are
encouraged to report negative side effects of prescription drugs to
the FDA. Visit MedWatch, or call 1-800-FDA-1088.
Please see the full Prescribing Information
and Medication Guide for SOLIRIS, including Boxed
WARNING regarding serious and life-threatening meningococcal
infections.
Notes
PNH
PNH is a rare, chronic, progressive and potentially
life-threatening blood disorder. It is characterized by red blood
cell destruction within blood vessels (also known as intravascular
hemolysis) and white blood cell and platelet activation, which can
result in thrombosis (blood clots).2-4
PNH is caused by an acquired genetic mutation that may happen
any time after birth and results in the production of abnormal
blood cells that are missing important protective blood cell
surface proteins. These missing proteins enable the complement
system, which is part of the immune system and is essential to the
body’s defense against infection, to ‘attack’ and destroy or
activate these abnormal blood cells.2 Living with PNH can be
debilitating, and signs and symptoms may include blood clots,
abdominal pain, difficulty swallowing, erectile dysfunction,
shortness of breath, excessive fatigue, anemia and dark-colored
urine.2,10,14
Clinically Significant EVH
EVH, the removal of red blood cells outside of the blood
vessels, can sometimes occur in PNH patients who are treated with
C5 inhibitors.15,16 Since C5 inhibition enables PNH red blood cells
to survive and circulate, EVH may occur when these now surviving
PNH red blood cells are marked by proteins in the complement system
for removal by the spleen and liver.2,4,6 Patients with PNH with
EVH may continue to experience anemia, which can have various
causes, and may require blood transfusions.15-18 A small subset of
people living with PNH who are treated with a C5 inhibitor
experience clinically significant EVH, which can result in
continued symptoms of anemia and require blood
transfusions.2,10-12
ALPHA
ALPHA is a pivotal, global Phase III trial designed as a
superiority study to evaluate the efficacy and safety of danicopan
as an add-on to C5 inhibitor therapy eculizumab or ravulizumab-cwvz
in patients with PNH who experience clinically significant EVH. In
the double-blind, placebo-controlled, multiple-dose trial, patients
were enrolled and randomized to receive danicopan or placebo (2:1)
in addition to their ongoing eculizumab or ravulizumab-cwvz therapy
for 12 weeks. A prespecified interim analysis was performed once 63
randomized patients had completed 12 weeks of the primary
evaluation period or discontinued treatment as of June 28, 2022. At
12 weeks, patients on placebo plus a C5 inhibitor were switched to
danicopan plus eculizumab or ravulizumab-cwvz, and patients on
danicopan plus eculizumab or ravulizumab-cwvz remained on treatment
for an additional 12 weeks. Patients who completed both treatment
periods (24 weeks) had the option to participate in a two-year
long-term extension period and continue to receive danicopan in
addition to eculizumab or ravulizumab-cwvz. The open-label period
of the study is still ongoing.5,19
Danicopan
Danicopan is an investigational oral medicine in development as
an add-on to C5 inhibitor therapy eculizumab or ravulizumab-cwvz
for patients with PNH who experience clinically significant EVH. It
is designed to selectively inhibit Factor D, a complement system
protein that plays a key role in the amplification of the
complement system response. Danicopan has been granted Breakthrough
Therapy designation by the US Food and Drug Administration and
PRIority MEdicines (PRIME) status by the European Medicines Agency.
Danicopan has also been granted Orphan Drug Designation in the US,
EU and Japan for the treatment of PNH. Alexion is also evaluating
danicopan as a potential monotherapy for geographic atrophy in a
Phase II clinical trial.
ULTOMIRIS® (ravulizumab-cwvz)
ULTOMIRIS® (ravulizumab-cwvz), the first and only long-acting C5
complement inhibitor, provides immediate, complete and sustained
complement inhibition. The medication works by inhibiting the C5
protein in the terminal complement cascade, a part of the body’s
immune system. When activated in an uncontrolled manner, the
complement cascade over-responds, leading the body to attack its
own healthy cells. ULTOMIRIS is administered intravenously every
eight weeks in adult patients, following a loading dose.
ULTOMIRIS is approved in the US, EU and Japan for the treatment
of certain adults with generalized myasthenia gravis (gMG).
ULTOMIRIS is also approved in the US, EU and Japan for the
treatment of certain adults with PNH and for certain children with
PNH in the US and EU.
Additionally, ULTOMIRIS is approved in the US, EU and Japan for
certain adults and children with atypical hemolytic uremic syndrome
to inhibit complement-mediated thrombotic microangiopathy
(aHUS).
Further, ULTOMIRIS is approved in the EU and Japan for the
treatment of certain adults with neuromyelitis optica spectrum
disorder (NMOSD).
As part of a broad development program, ULTOMIRIS is being
assessed for the treatment of additional hematology and neurology
indications.
SOLIRIS® (eculizumab)
SOLIRIS® (eculizumab) is a first-in-class C5 complement
inhibitor. The medication works by inhibiting the C5 protein in the
terminal complement cascade, a part of the body’s immune system.
When activated in an uncontrolled manner, the terminal complement
cascade over-responds, leading the body to attack its own healthy
cells. SOLIRIS is administered intravenously every two weeks,
following an introductory dosing period.
SOLIRIS is approved in the US, EU, Japan and China for the
treatment of patients with PNH and aHUS.
Additionally, SOLIRIS is approved in Japan and the EU for the
treatment of certain adult and pediatric patients with gMG and in
the US and China for certain adults with gMG.
Further, SOLIRIS is approved in the US, EU, Japan and China for
the treatment of certain adults with NMOSD.
SOLIRIS is not indicated for the treatment of patients with
Shiga-toxin E. coli-related hemolytic uremic syndrome.
Alexion
Alexion, AstraZeneca Rare Disease, is the group within
AstraZeneca focused on rare diseases, created following the 2021
acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare
diseases for more than 30 years, Alexion is focused on serving
patients and families affected by rare diseases and devastating
conditions through the discovery, development and commercialization
of life-changing medicines. Alexion focuses its research efforts on
novel molecules and targets in the complement cascade and its
development efforts on hematology, nephrology, neurology, metabolic
disorders, cardiology and ophthalmology. Headquartered in Boston,
Massachusetts, Alexion has offices around the globe and serves
patients in more than 50 countries. For more information, please
visit www.alexion.com.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialization of prescription medicines in
Oncology, Rare Diseases and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit www.astrazeneca-us.com and follow
the Company on social media @AstraZeneca.
References
- Kulasekararaj, AG, et al. Danicopan as add-on therapy to
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