- Ongoing Phase 3 study demonstrated PK
non-inferiority of ULTOMIRIS SC versus ULTOMIRIS IV at Day 71 -
- Preliminary safety data consistent with the
known safety profile of ULTOMIRIS -
Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced
topline results from a Phase 3 study of weekly self-administered
subcutaneous (SC) ULTOMIRIS® (ravulizumab-cwvz) in adults with
paroxysmal nocturnal hemoglobinuria (PNH). The ongoing study met
its primary objective of pharmacokinetic (PK)-based non-inferiority
of ULTOMIRIS SC versus intravenous (IV) ULTOMIRIS at Day 71.
Pending completion of the study, including collection of 12-month
safety data as agreed to with the U.S. Food and Drug Administration
(FDA), Alexion now expects to file for approval in the U.S. and
E.U. for the ULTOMIRIS SC formulation and device combination in PNH
and atypical hemolytic uremic syndrome (aHUS) in the third quarter
of 2021.
“These data demonstrate that subcutaneous ULTOMIRIS may offer
the same benefits of immediate, complete and sustained complement
inhibition as the intravenous formulation, while also providing an
additional treatment choice for those who would rather
self-administer their medicine,” said John Orloff, M.D., Executive
Vice President and Head of Research and Development at Alexion.
“Delivered via a rapid, patient-friendly delivery device,
subcutaneous ULTOMIRIS is an example of Alexion’s continued
commitment to innovating for patients. It has the potential to be
the first subcutaneous treatment option for both PNH and aHUS and
may also offer improved quality of life for patients.”
About the Phase 3 Study
This ongoing global Phase 3, randomized, open-label,
parallel-group, multicenter study is evaluating ULTOMIRIS SC
compared with ULTOMIRIS IV. The study enrolled 136 adults with PNH
who are clinically stable and have previously been treated with
SOLIRIS® (eculizumab) for at least three months prior to study
entry. The study’s primary objective is to evaluate PK
noninferiority of ULTOMIRIS SC compared with ULTOMIRIS IV, as
assessed by ULTOMIRIS serum trough concentration at Day 71. The
study remains ongoing to assess secondary endpoints, including
safety, immunogenicity and various PK/PD, quality of life, device
performance and efficacy measures.
Patients were stratified by weight groups (≥ 40 to < 60 kg
and ≥ 60 to < 100 kg) and then randomized 2:1 to receive either
ULTOMIRIS SC or ULTOMIRIS IV. All patients received an initial IV
loading dose on Day 1. On Day 15, patients in the ULTOMIRIS SC
group began receiving a once-weekly self-administered fixed-dose of
ULTOMIRIS SC, and patients in the ULTOMIRIS IV group received a
single infusion of the approved weight-based IV dose.
The study met its primary objective, with ULTOMIRIS SC
demonstrating PK-based non-inferiority versus ULTOMIRIS IV at Day
71 (p < 0.0001 for non-inferiority in serum ULTOMIRIS trough
concentration - Ctrough). Serum free C5 concentrations were
maintained below the target threshold in all patients, and mean
lactate dehydrogenase levels remained stable below the upper limit
of normal. Preliminary safety data through the 71-day randomized
treatment period of the study were consistent with the known safety
profile of ULTOMIRIS and did not result in any unexpected safety
findings. No adverse events led to withdrawal of study drug in
either arm. No serious adverse device effects or meningococcal
cases were reported, and no anti-drug antibodies were observed.
Of the 135 patients who completed the randomized controlled
treatment portion of the study, all but one participant chose to
continue in the ongoing SC-only extension period, where all
patients are receiving weekly ULTOMIRIS SC for up to an additional
182 weeks. The extension period will provide 12 months of safety
data required for regulatory submissions to applicable health
authorities, now anticipated in the third quarter of 2021 to
accommodate all regulatory requirements for this combination device
filing.
About ULTOMIRIS SC Delivery
Each weekly dose of ULTOMIRIS SC is delivered via two
specifically designed, patient-friendly devices that adhere to the
body and can be self-administered with the push of a button. The
devices can be used either concurrently or sequentially, and when
administered concurrently, a full dose of ULTOMIRIS SC can be
delivered hands-free in approximately 10 minutes. Previously
approved by the FDA for use with another therapy, the single-use
SmartDose® device contains a pre-filled cartridge and was developed
in collaboration with West Pharmaceutical Services, Inc. to provide
patients with a more flexible ULTOMIRIS treatment option.
About Paroxysmal Nocturnal Hemoglobinuria (PNH)
Paroxysmal nocturnal hemoglobinuria (PNH) is a serious
ultra-rare blood disorder with devastating consequences. It is
characterized by the destruction of red blood cells, which is also
referred to as hemolysis. PNH occurs when the complement system—a
part of the body’s immune system—over-responds, leading the body to
attack its own red blood cells. PNH often goes unrecognized, with
delays in diagnosis from one to more than five years. Patients with
PNH may experience a range of symptoms, such as fatigue, difficulty
swallowing, shortness of breath, abdominal pain, erectile
dysfunction, dark-colored urine and anemia. The most devastating
consequence of chronic hemolysis is the formation of blood clots,
which can occur in blood vessels throughout the body, damage vital
organs, and potentially lead to premature death. PNH can strike men
and women of all races, backgrounds and ages without warning, with
an average age of onset in the early 30s.
About Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare
disease that can cause progressive injury to vital organs,
primarily the kidneys, via damage to the walls of blood vessels and
blood clots. Atypical HUS occurs when the complement system—a part
of the body’s immune system—over-responds, leading the body to
attack its own healthy cells. Atypical HUS can cause sudden organ
failure or a slow loss of function over time—potentially resulting
in the need for a transplant, and in some cases, death. Atypical
HUS affects both adults and children, and many patients present in
critical condition, often requiring supportive care, including
dialysis, in an intensive care unit. The prognosis of aHUS can be
poor in many cases, so a timely and accurate diagnosis—in addition
to treatment—is critical to improving patient outcomes. Available
tests can help distinguish aHUS from other hemolytic diseases with
similar symptoms.
About ULTOMIRIS® (ravulizumab‑cwvz)
ULTOMIRIS® (ravulizumab-cwvz) is the first and only long-acting
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
complement cascade over-responds, leading the body to attack its
own healthy cells. ULTOMIRIS is administered intravenously every
eight weeks or every four weeks for pediatric patients less than 20
kg, following a loading dose. ULTOMIRIS is approved in the United
States (U.S.), European Union (EU) and Japan as a treatment for
adults with paroxysmal nocturnal hemoglobinuria (PNH) and in the
U.S. for atypical hemolytic uremic syndrome (aHUS) to inhibit
complement-mediated thrombotic microangiopathy (TMA) in adult and
pediatric (one month of age and older) patients.
U.S. INDICATIONS & IMPORTANT SAFETY INFORMATION FOR
ULTOMIRIS (ravulizumab-cwvz) 300 mg / 30 mL injection for
intravenous use
U.S. INDICATIONS
ULTOMIRIS is a prescription medicine called a monoclonal
antibody. ULTOMIRIS is used to treat adults with a disease called
Paroxysmal Nocturnal Hemoglobinuria (PNH). ULTOMIRIS is used to
treat 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). It is not known if ULTOMIRIS is safe
and effective in children with PNH. It is not known if ULTOMIRIS is
safe and effective in children younger than 1 month of age.
U.S. IMPORTANT SAFETY INFORMATION
ULTOMIRIS 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. One’s doctor will decide
if additional meningococcal vaccination is needed. Meningococcal
vaccines reduce the risk of meningococcal infection but do not
prevent all meningococcal infections. 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. One’s doctor will
give a Patient Safety Card about the risk of meningococcal
infection. Carry the card at all times during treatment and for 8
months after your ULTOMIRIS dose.
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 doctor. Call the doctor right away if one has
any new signs or symptoms of infection.
Do not receive ULTOMIRIS if one has a meningococcal infection,
or has not been vaccinated against meningococcal infection unless
the doctor decides that urgent treatment with ULTOMIRIS is
needed.
Before one receives ULTOMIRIS, tell the doctor about all of the
medical conditions, including if one: has 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 an
unborn baby. It is not known if ULTOMIRIS passes into the breast
milk. One should not breastfeed 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 medicines 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 and 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 red blood cell count,
tiredness, blood in the urine, stomach-area (abdomen) pain,
shortness of breath, blood clots, trouble swallowing, and erectile
dysfunction (ED) in males. If one has aHUS, the doctor will need to
monitor closely for at least 12 months after stopping treatment for
signs of worsening aHUS symptoms or problems related to a type of
abnormal clotting and breakdown of the 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. If one misses an ULTOMIRIS infusion, call the
doctor right away.
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, feeling faint or
discomfort in the arms or legs. 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 in people treated for
PNH are upper respiratory infection and headache. The most common
side effects of ULTOMIRIS in people with aHUS are upper respiratory
infections, diarrhea, nausea, vomiting, headache, high blood
pressure, and fever.
Please see the accompanying full Prescribing Information and Medication Guide for
ULTOMIRIS, including Boxed WARNING regarding serious and
life-threatening meningococcal infections/sepsis.
About Alexion
Alexion is a global biopharmaceutical company focused on serving
patients and families affected by rare and devastating diseases
through the discovery, development and commercialization of
life-changing medicines. 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) and atypical
hemolytic uremic syndrome (aHUS), as well as the first and only
approved complement inhibitor to treat anti-acetylcholine receptor
(AchR) antibody-positive generalized myasthenia gravis (gMG) and
neuromyelitis optica spectrum disorder (NMOSD). Alexion also has
two highly innovative enzyme replacement therapies for patients
with life-threatening and ultra-rare metabolic disorders,
hypophosphatasia (HPP) and lysosomal acid lipase deficiency
(LAL-D). In addition, the company is developing several
mid-to-late-stage therapies, including a copper-binding agent for
Wilson disease, an anti-neonatal Fc receptor (FcRn) antibody for
rare Immunoglobulin G (IgG)-mediated diseases and an oral Factor D
inhibitor as well as several early-stage therapies, including one
for light chain (AL) amyloidosis, a second oral Factor D inhibitor
and a third complement inhibitor. Alexion focuses its research
efforts on novel molecules and targets in the complement cascade
and its development efforts on the core therapeutic areas of
hematology, nephrology, neurology, metabolic disorders and
cardiology. Headquartered in Boston, Massachusetts, Alexion has
offices around the globe and serves patients in more than 50
countries. This press release and further information about Alexion
can be found at: www.alexion.com.
[ALXN-G]
Forward-Looking Statement
This press release contains forward-looking statements that
involve risks and uncertainties relating to future events and the
future performance of Alexion, including statements related to: the
efficacy and safety of ULTOMIRIS SC and device combination for PNH
and aHUS patients; the anticipated timing for the filing of
ULTOMIRIS SC formulation and device combination for regulatory
approval for the treatment of PNH and aHUS in the U.S. and the
E.U.; the successful completion of the Phase 3 study of ULTOMIRIS
SC; that ULTOMIRIS SC may offer the same benefits of immediate,
complete and sustained complement inhibition as the intravenous
formulation, while also providing an additional treatment choice
for those who would rather self-administer their medicine at home
and that ULTOMIRIS SC and device combination has the potential to
be the first subcutaneous treatment option for both PNH and aHUS
patients and may also offer improved quality of life for patients
and statements related to SC ULTOMIRIS delivery. Forward-looking
statements are subject to factors that may cause Alexion's results
and plans to differ materially from those expected by these forward
looking statements, including for example: ULTOMIRIS SC and device
combination may not be approved in the U.S. or the E.U. or
regulatory authorities may be delayed in providing their approval;
the anticipated safety profile and the benefits of ULTOMIRIS SC for
PNH and aHUS patients may not be realized (and the results of the
clinical trials may not be indicative of the results once
approved); results of clinical trials may not be sufficient to
satisfy regulatory authorities in order to approve ULTOMIRIS SC and
device combination as a treatment for PNH or aHUS (or they may
request additional trials or additional information); results in
clinical trials may not be indicative of results from later stage
or larger clinical trials (or in broader patient populations once
the product is approved for use by regulatory agencies); the device
used to administer ULTOMIRIS SC may not be available or may not be
approved by regulators; the possibility that results of clinical
trials are not predictive of safety and efficacy and potency of our
products (or we fail to adequately operate or manage our clinical
trials) which could cause us to discontinue sales of the product
(or halt trials, delay or prevent us from making regulatory
approval filings or result in denial of approval of our product
candidates); the severity of the impact of the COVID-19 pandemic on
Alexion’s business, including on commercial and clinical
development programs; unexpected delays in clinical trials;
unexpected concerns regarding products and product candidates that
may arise from additional data or analysis obtained during clinical
trials or obtained once used by patients following product
approval; future product improvements may not be realized due to
expense or feasibility or other factors; delays (expected or
unexpected) in the time it takes regulatory agencies to review and
make determinations on applications for the marketing approval of
our products; inability to timely submit (or failure to submit)
future applications for regulatory approval for our products and
product candidates; inability to timely initiate (or failure to
initiate) and complete future clinical trials due to safety issues,
IRB decisions, CMC-related issues, expense or unfavorable results
from earlier trials (among other reasons); our dependence on sales
from our principal product (SOLIRIS); future competition from
biosimilars and novel products; decisions of regulatory authorities
regarding the adequacy of our research, marketing approval or
material limitations on the marketing of our products; delays or
failure of product candidates to obtain regulatory approval; delays
or the inability to launch product candidates due to regulatory
restrictions, anticipated expense or other matters; interruptions
or failures in the manufacture and supply of our products and our
product candidates; failure to satisfactorily address matters
raised by regulatory agencies regarding our products and product
candidates; uncertainty of long-term success in developing,
licensing or acquiring other product candidates or additional
indications for existing products; inability to complete
acquisitions or grow the product pipeline through acquisitions
(including due to failure to obtain antitrust approvals); the
possibility that current rates of adoption of our products are not
sustained; the adequacy of our pharmacovigilance and drug safety
reporting processes; failure to protect and enforce our data,
intellectual property and proprietary rights and the risks and
uncertainties relating to intellectual property claims, lawsuits
and challenges against us (including intellectual property lawsuits
relating to ULTOMIRIS brought by third parties); the risk that
third party payors (including governmental agencies) will not
reimburse or continue to reimburse for the use of our products at
acceptable rates or at all; failure to realize the benefits and
potential of investments, collaborations, licenses and
acquisitions; the possibility that expected tax benefits will not
be realized; potential declines in sovereign credit ratings or
sovereign defaults in countries where we sell our products; delay
of collection or reduction in reimbursement due to adverse economic
conditions or changes in government and private insurer regulations
and approaches to reimbursement; adverse impacts on our supply
chain, clinical trials, manufacturing operations, financial
results, liquidity, hospitals, pharmacies and health care systems
from natural disasters and global pandemics, including COVID-19;
uncertainties surrounding legal proceedings, company investigations
and government investigations, including investigations of Alexion
by the U.S. Securities and Exchange Commission; the risk that
estimates regarding the number of patients with PNH, aHUS, gMG,
NMOSD, HPP and LAL-D and other indications we are pursuing are
inaccurate; the risks of changing foreign exchange rates; risks
relating to the potential effects of the Company's restructuring;
risks related to the pending acquisition of Portola
Pharmaceuticals, the acquisition of Achillion and other companies
and co-development efforts; and a variety of other risks set forth
from time to time in Alexion's filings with the SEC, including but
not limited to the risks discussed in Alexion's Quarterly Report on
Form 10-Q for the period ended March 31, 2020 and in our other
filings with the SEC. Alexion disclaims any obligation to update
any of these forward-looking statements to reflect events or
circumstances after the date hereof, except when a duty arises
under law.
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Alexion Contacts: Media Megan Goulart,
857-338-8634 Executive Director, Corporate Communications
Investors Chris Stevo, 857-338-9309 Head of Investor
Relations
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