– ULTOMIRIS demonstrated consistent efficacy and safety through 52
weeks, with no cases of breakthrough hemolysis (BTH) associated with
incomplete C5 complement inhibition –
– Nearly all surveyed patients preferred ULTOMIRIS over SOLIRIS®
(eculizumab) –
BOSTON–(BUSINESS WIRE)–Alexion
Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced the presentation
of new data demonstrating that ULTOMIRIS® (ravulizumab), the
first and only long-acting C5 complement inhibitor administered every
eight weeks, provided consistent efficacy and safety through 52 weeks in
the extension1 of the Phase 3 study of ULTOMIRIS and SOLIRIS®
(eculizumab) in complement inhibitor-naïve, adult patients with
paroxysmal nocturnal hemoglobinuria (PNH).2 Sustained
efficacy of ULTOMIRIS was observed on the co-primary endpoints of
transfusion avoidance and normalization of lactate dehydrogenase (LDH)
levels and the secondary endpoints of LDH level reduction and
breakthrough hemolysis (BTH). In an additional sub-study, nearly all
patients preferred ULTOMIRIS over SOLIRIS.3 The data will be
presented at the Annual Congress of the European Hematology Association
(EHA), taking place June 13-19, 2019 in Amsterdam, Netherlands.
LDH level normalization and reduction are direct markers for reduced
hemolysis in PNH, a severe, ultra-rare disease characterized by
complement-mediated intravascular hemolysis. PNH can cause a wide range
of debilitating symptoms and complications, including thrombosis, which
can occur throughout the body and result in organ damage and premature
death.4,5,6,7,8,9,10,11 Incomplete inhibition of the C5
complement protein can increase the risk of BTH and related serious
complications.12,13,14,15
“The confirmation of consistent efficacy and safety through 52 weeks
with only six or seven infusions per year instead of 26 with SOLIRIS
makes ULTOMIRIS a very compelling new therapy for patients with PNH,”
said Professor Hubert Schrezenmeier, M.D., Medical Director of the
Institute of Transfusion Medicine and the Institute for Clinical
Transfusion Medicine and Immunogenetics, German Red Cross Blood
Transfusion Service Baden-Württemberg-Hessen and University Hospital
Ulm, Germany, study investigator and presenting author. “I am impressed
with the continuing complete C5 inhibition in all patients receiving
ULTOMIRIS and the absence of breakthrough hemolysis associated with
incomplete C5 inhibition. This makes me hopeful that we can reduce the
potentially devastating consequences of returning PNH symptoms.”
All patients in the initial ULTOMIRIS group of the extension study
maintained complete C5 inhibition through 52 weeks, and no patient
experienced BTH associated with incomplete C5 inhibition. All patients
who had experienced incomplete C5 inhibition while receiving SOLIRIS in
the first 26 weeks achieved complete C5 inhibition after the switch to
ULTOMIRIS in the extension phase. No patient experienced BTH associated
with incomplete C5 inhibition between weeks 27 and 52 after switching to
ULTOMIRIS compared to six percent while receiving SOLIRIS in the first
26 weeks.1
“We continue to expand the body of clinical evidence supporting the
potential of ULTOMIRIS to become the new standard of care for patients
with PNH,” said John Orloff, M.D., Executive Vice President and Head of
Research & Development at Alexion. “SOLIRIS, the first approved therapy
for PNH, was a breakthrough for patients for whom only supportive care
had been available before. With ULTOMIRIS, we want to enable patients to
live their lives more freely thanks to maximal hemolysis control with
established safety and reduced treatment burden.”
The most common adverse events occurred less frequently in the extension
phase than during the initial treatment phase where the safety profile
of ULTOMIRIS was consistent with that of SOLIRIS.2 The most
common treatment-emergent adverse events in the extension phase were
upper respiratory tract infection (in the initial ULTOMIRIS arm) and
nasopharyngitis (in the initial SOLIRIS arm). The most frequently
observed serious adverse event was pyrexia. One patient in the initial
SOLIRIS arm died from lung cancer (unrelated to SOLIRIS treatment).
There was no case of meningococcal infection observed.1,2
ULTOMIRIS was studied in the largest-ever Phase 3 program in PNH. The
entire clinical development program for ULTOMIRIS in PNH to date
represents more than 800 patient years of experience.
Additional data to be presented at the EHA congress indicate a very
strong patient preference for ULTOMIRIS over SOLIRIS.3
According to results from a sub-study in the ULTOMIRIS Phase 3 extension
in patients who had been stable on SOLIRIS before,16 nearly
all patients (93%) preferred ULTOMIRIS due to reduced infusion
frequency, ability to plan activities, overall quality of life,
convenience of treatment, and effectiveness of medication until the next
infusion compared to SOLIRIS.3
New results from the International PNH Registry will also be presented
at the EHA congress. These data suggest that a change in clone size does
not change the increased risk of major adverse vascular events in PNH,17
and that complement inhibition with SOLIRIS does not change the
effectiveness of concomitant immunosuppressive therapy in patients with
PNH and aplastic anemia (AA).18
The U.S. Food and Drug Administration (FDA) approved ULTOMIRIS for adult
patients with PNH on December
21, 2018. The European Commission (EC) is reviewing the
recommendation by the European Medicines Agency’s (EMA) Committee for
Medicinal Products for Human Use (CHMP) from April
26, 2019 to approve ULTOMIRIS as a treatment for adult patients with
PNH and typically delivers its final decision within two months. The
Japanese Ministry of Health, Labour and Welfare (MHLW) is reviewing the
recommendation by the Pharmaceuticals and Medical Devices Agency’s
(PMDA) Drug Committee (BUKAI) to approve ULTOMIRIS as a treatment for
patients with PNH and is anticipated to deliver a decision in late June.
One-Year
Efficacy of Ravulizumab (ALXN1210) in Adult Patients with Paroxysmal
Nocturnal Hemoglobinuria Naive to Complement Inhibitors, EHA
Congress, June 13-16, 2019 Amsterdam, Netherlands, oral presentation,
June 15, 2019, 12:00 p.m., abstract S863.1
Patient
Preferences for the Treatment of Paroxysmal Nocturnal Hemoglobinuria:
Results of a Patient Survey of Ravulizumab (ALXN1210) and Eculizumab,
EHA Congress, June 13-16, 2019 Amsterdam, Netherlands, poster
presentation, June 14, 2019, 5:30 p.m., abstract PF734.3
Change
in Clone Size Does Not Predict Risk of Major Adverse Vascular Events:
Results from the International PNH Registry, EHA Congress, June
13-16, 2019 Amsterdam, Netherlands, oral presentation, June 15, 2019,
12:30 p.m., abstract S865.17
No
Change in the Effectiveness of Immunosuppressive Therapy in Patients
with PNH and AA Receiving concomitant Eculizumab, EHA Congress, June
13-16, 2019 Amsterdam, Netherlands, poster presentation, June 15, 2019,
5:30 p.m., abstract PS1117.18
About the extension1 of the Phase 3 study in
complement-naïve, adult patients with PNH2
At
the end of the 26-week Phase 3 study,2 all patients (246; 125
on ULTOMIRIS, 121 on SOLIRIS) had the option to receive ULTOMIRIS every
eight weeks for up to two years. The aim of this extension study is to
monitor the durability of efficacy in the initial ULTOMIRIS group, the
efficacy of ULTOMIRIS in the initial SOLIRIS group after the switch to
ULTOMIRIS and the safety of ULTOMIRIS in all patients. A total of 243
patients (124 from the initial ULTOMIRIS group, 119 from the initial
SOLIRIS group) were followed. Results for the co-primary endpoints of
transfusion avoidance and LDH level normalization and the secondary
endpoints of percentage change from baseline in LDH levels and
proportion of patients with BTH are provided descriptively. Complete C5
inhibition was defined as plasma levels of free C5 ≤0.5 μg/ml.1
About the patient preference study3
At the
end of the 26-week Phase 3 study in adult patients with PNH who had been
clinically stable on SOLIRIS for at least 6 months,16 all
patients (195) were given the option to continue receiving ULTOMIRIS
every eight weeks for up to two years. The patient preference study
enrolled patients from the extension study who had received at least two
doses of ULTOMIRIS. Patient treatment preference was evaluated at one
time point using an 11-item PNH-specific Patient Preference
Questionnaire (PNH-PPQ©). The 11 questions included one
question on overall treatment preference, nine questions on preference
based on treatment characteristics, one question on the most important
treatment characteristic for the overall treatment preference, four
questions on aspects of treatment with SOLIRIS and four matching
questions for ULTOMIRIS. Of 98 patients enrolled, 95 patients from eight
countries (European Union, North America, and Australia) completed
PNH-PPQs per protocol.3
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal
nocturnal hemoglobinuria (PNH) is a chronic, progressive, debilitating
and life-threatening ultra-rare blood disorder characterized by
intravascular hemolysis (destruction of red blood cells) that is
mediated by an uncontrolled activation of the complement system, a part
of the immune system.4,5,19 PNH can strike men and women of
all races, backgrounds and ages without warning, with an average age of
onset in the early 30s.4,20 PNH often goes unrecognized, with
delays in diagnosis ranging from one to more than five years.21
Patients with PNH may experience a wide range of signs and symptoms,
such as fatigue, difficulty swallowing, shortness of breath, abdominal
pain, erectile dysfunction, dark-colored urine and anemia.6,7,8,9,10,11,19
The most devastating consequence of chronic intravascular hemolysis is
thrombosis, which can occur in blood vessels throughout the body, damage
vital organs and cause premature death.22 The first
thrombotic event can be fatal.4,20,23 Despite historical
supportive care, including transfusion and anticoagulation management,
20 to 35 percent of patients with PNH die within five to 10 years of
diagnosis.24,25 Patients with certain types of hemolytic
anemia, bone marrow disorders and unexplained venous or arterial
thrombosis are at increased risk of PNH.14,19,26,27,28,29
About ULTOMIRIS®
ULTOMIRIS
(ravulizumab-cwvz), the first and only long-acting C5 inhibitor
administered every eight weeks, is approved in the U.S. as a treatment
for adults with paroxysmal nocturnal hemoglobinuria (PNH). ULTOMIRIS
works by inhibiting the C5 protein in the terminal complement cascade, a
part of the body’s immune system. The terminal complement cascade, when
activated in an uncontrolled manner, plays a role in severe ultra-rare
disorders like PNH, atypical hemolytic uremic syndrome (aHUS),
anti-acetylcholine receptor (AchR) antibody-positive myasthenia gravis
(MG) and anti-aquaporin-4 (AQP4) auto-antibody-positive neuromyelitis
optica spectrum disorder (NMOSD). Regulatory authorities in the European
Union (EU) and Japan are reviewing applications for the approval of
ULTOMIRIS as a treatment for adult patients and patients with PNH,
respectively. In Phase 3 clinical studies in complement inhibitor-naïve
patients with PNH2 and patients with PNH who had been stable
on SOLIRIS® (eculizumab),16 intravenous treatment
with ULTOMIRIS every eight weeks demonstrated non-inferiority to
intravenous treatment with SOLIRIS every two weeks on all endpoints.
The Phase 3 study of ULTOMIRIS, administered intravenously every eight
weeks in adult patients with aHUS, met
its primary objective. Alexion has submitted a supplemental
Biologics License Application (sBLA) to the U.S. Food and Drug
Administration (FDA) for approval of ULTOMIRIS as a treatment for
patients with aHUS and plans to submit similar applications in the EU
and Japan later in 2019. ULTOMIRIS is also currently being evaluated in
a Phase 3 clinical study in children and adolescents with aHUS,
administered intravenously every eight weeks. Alexion has initiated a
Phase 3 study of ULTOMIRIS, intravenously administered every eight
weeks, as a potential treatment for patients with generalized MG (gMG),
and is planning to initiate a Phase 3 in patients with NMOSD. In
addition, Alexion has initiated Phase 3 studies of ULTOMIRIS delivered
subcutaneously once per week as a potential treatment for patients with
PNH and aHUS.
ULTOMIRIS has received Orphan Drug Designation (ODD) for the treatment
of patients with PNH in the U.S. and Japan and for the subcutaneous
treatment of patients with aHUS in the U.S.
U.S. Indication of ULTOMIRIS®
ULTOMIRIS
(ravulizumab-cwvz) is a prescription medicine called a monoclonal
antibody. ULTOMIRIS is used to treat adults with a disease called
paroxysmal nocturnal hemoglobinuria (PNH). It is not known if ULTOMIRIS
is safe and effective in children.
U.S. Important Safety Information for ULTOMIRIS®
ULTOMIRIS
(ravulizumab-cwvz) is a medicine that affects the immune system.
ULTOMIRIS can lower the ability of the immune system to fight
infections. ULTOMIRIS increases the chance of getting serious and
life-threatening meningococcal infections. Meningococcal infections may
quickly become life-threatening and cause death if not recognized and
treated early.
Meningococcal vaccines must be received at least 2 weeks before the
first dose of ULTOMIRIS if one has not already had this vaccine. If
one’s doctor decided that urgent treatment with ULTOMIRIS is needed,
meningococcal vaccination should be administered as soon as possible. If
one has not been vaccinated and ULTOMIRIS therapy must be initiated
immediately, 2 weeks of antibiotics should also be administered with the
vaccinations. If one had a meningococcal vaccine in the past, additional
vaccination might be needed before starting ULTOMIRIS. Call one’s doctor
or get emergency medical care right away if any of these signs and
symptoms of a meningococcal infection occur: headache with nausea or
vomiting, headache with a stiff neck or stiff back, fever and a rash,
muscle aches with flu-like symptoms, headache and fever, fever,
confusion, and eyes sensitive to light.
ULTOMIRIS is only available through a program called the ULTOMIRIS
REMS.
ULTOMIRIS may also increase the risk of other types of serious
infections. People who take ULTOMIRIS may have an increased risk of
getting infections caused by Streptococcus pneumoniae and Haemophilus
influenzae. Certain people may also have an increased risk of
gonorrhea infection. To find out if one is at risk for gonorrhea
infection, about gonorrhea prevention, and regular testing, talk to the
healthcare provider. Call the healthcare provider right away if one has
any new signs or symptoms of infection.
Before one receives ULTOMIRIS, tell the doctor about all of the medical
conditions, including if one: has an infection or fever, is pregnant or
plans to become pregnant, and is breastfeeding or plans to breastfeed.
It is not known if ULTOMIRIS will harm an unborn baby. It is not known
if ULTOMIRIS passes into the breast milk. One should not breast feed
during treatment and for 8 months after one’s final dose of ULTOMIRIS.
Tell the doctor about all the medicines one takes, including
prescription and over-the-counter medicines, vitamins, and herbal
supplements. ULTOMIRIS and other medicines can affect each other causing
side effects. Know the medications one takes and the vaccines one
receives. Keep a list of them to show the doctor and pharmacist when one
gets a new medicine.
If one stops receiving ULTOMIRIS, the doctor will need to monitor
closely for at least 16 weeks after one stops ULTOMIRIS. Stopping
ULTOMIRIS may cause breakdown of the red blood cells due to PNH.
Symptoms or problems that can happen due to red blood cell breakdown
include: drop in the number of the red blood cell count, tiredness,
blood in the urine, stomach-area (abdomen) pain, blood clots, shortness
of breath, trouble swallowing, and erectile dysfunction (ED) in males.
ULTOMIRIS can cause serious side effects including infusion reactions.
Infusion reactions may happen during one’s ULTOMIRIS infusion. Symptoms
of an infusion reaction with ULTOMIRIS may include lower back pain, pain
with the infusion, or feeling faint. Tell the doctor or nurse right away
if these symptoms develop, or any other symptoms during the ULTOMIRIS
infusion that may mean one is having a serious infusion reaction,
including: chest pain, trouble breathing or shortness of breath,
swelling of the face, tongue, or throat, and feel faint or pass out.
One’s doctor will treat the symptoms as needed. The most common side
effects of ULTOMIRIS are upper respiratory infection and headache.
For more information, please see the full U.S. Prescribing
Information and Medication
Guide for ULTOMIRIS, including Boxed WARNING regarding serious and
life-threatening meningococcal infections/sepsis, also available at: www.ultomiris.com.
U.S. Indication for SOLIRIS®
SOLIRIS
(eculizumab) is a prescription medicine called a monoclonal antibody.
SOLIRIS is 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]), and adults with a disease called generalized
Myasthenia Gravis (gMG) who are anti-acetylcholine receptor (AchR)
antibody positive. It is not known if SOLIRIS is safe and effective in
children with PNH or gMG.
U.S. Important Safety Information for SOLIRIS®
SOLIRIS
(eculizumab) is a medicine that affects the immune system. SOLIRIS can
lower the ability of the immune system to fight infections. SOLIRIS
increases the chance of getting serious and life-threatening
meningococcal infections. Meningococcal infections may quickly become
life-threatening and cause death if not recognized and treated early.
Meningococcal vaccines must be received at least 2 weeks before the
first dose of SOLIRIS if one has not already had this vaccine. If one’s
doctor decided that urgent treatment with SOLIRIS is needed,
meningococcal vaccination should be administered as soon as possible. If
one has not been vaccinated and SOLIRIS therapy must be initiated
immediately, 2 weeks of antibiotics should also be administered with the
vaccinations. If one had a meningococcal vaccine in the past, additional
vaccination might be needed before starting SOLIRIS. Call one’s doctor
or get emergency medical care right away if any of these signs and
symptoms of a meningococcal infection occur: 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.
SOLIRIS is only available through a program called the SOLIRIS
REMS.
SOLIRIS may also increase the risk of other types of serious infections.
If one’s child is treated with SOLIRIS, make sure that the child
receives vaccinations against Streptococcus pneumoniae and Haemophilus
influenzae type b (Hib). Certain people may be at risk of serious
infections with gonorrhea. Talk to the doctor about whether one is at
risk for gonorrhea infection, about gonorrhea prevention, and regular
testing. Certain fungal infections (Aspergillus) may also happen if one
takes SOLIRIS and has a weak immune system or a low white blood cell
count.
Before one receives SOLIRIS, tell the doctor about all of the medical
conditions, including if one: has an infection or fever, is pregnant or
plans to become pregnant, and is breastfeeding or plans to breastfeed.
It is not known if SOLIRIS will harm an unborn baby. It is not known if
SOLIRIS passes into the breast milk.
Tell the doctor about all the medicines one takes, including
prescription and over-the-counter medicines, vitamins, and herbal
supplements. SOLIRIS and other medicines can affect each other causing
side effects.
It is important that one: has all recommended vaccinations before
starting SOLIRIS, receives 2 weeks of antibiotics if one immediately
starts SOLIRIS, and stays up-to-date with all recommended vaccinations
during treatment with SOLIRIS. Know the medications one takes and the
vaccines one receives. Keep a list of them to show the doctor and
pharmacist when one gets a new medicine.
If one has PNH, the doctor will need to monitor closely for at least 8
weeks after stopping SOLIRIS. Stopping treatment with SOLIRIS may cause
breakdown of the red blood cells due to PNH. Symptoms or problems that
can happen due to red blood cell breakdown include: drop in the number
of the red blood cell count, drop in the platelet counts, confusion,
kidney problems, blood clots, difficulty breathing, and chest pain.
If one has aHUS, the doctor will need to monitor closely for at least 12
weeks after stopping SOLIRIS 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, swellings in arms or legs and a drop in platelet count.
SOLIRIS can cause serious side effects including serious allergic
reactions. Serious allergic reactions can happen during one’s SOLIRIS
infusion. Tell the doctor or nurse right away if one gets any of these
symptoms during the SOLIRIS infusion: chest pain, trouble breathing or
shortness of breath, swelling of the face, tongue, or throat, and
feeling faint or pass out. If one has an allergic reaction to SOLIRIS,
the 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 the 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
the 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.
Please see the accompanying full U.S. Prescribing
Information and Medication
Guide for SOLIRIS, including Boxed WARNING regarding serious and
life-threatening meningococcal infections, also available at: www.soliris.net.
About Alexion
Alexion is a global biopharmaceutical company
focused on serving patients and families affected by rare diseases
through the discovery, development and commercialization of
life-changing therapies. As the global leader in complement biology and
inhibition for more than 20 years, Alexion has developed and
commercializes two approved complement inhibitors to treat patients with
paroxysmal nocturnal hemoglobinuria (PNH) as well as the first and only
approved complement inhibitor to treat atypical hemolytic uremic
syndrome (aHUS) and anti-acetylcholine receptor (AchR) antibody-positive
generalized myasthenia gravis (gMG), and is also developing it for
patients with neuromyelitis optica spectrum disorder (NMOSD).
Contacts
Alexion Pharmaceuticals, Inc.
Media
Arne Naeveke, PhD, +1
857-338-8597
Lauren Cettier, +41 44 457 4323
Investors
Susan
Altschuller, PhD, +1 857-338-8788