- Global study to enroll approximately 270
adults with COVID-19 and severe pneumonia or acute respiratory
distress syndrome -
- Company maintains commitment to supplying its
medicines to patients for currently approved indications -
Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced
plans to initiate a global Phase 3 study to investigate ULTOMIRIS®
(ravulizumab-cwvz) in a subset of adults with COVID-19 – those who
are hospitalized with severe pneumonia or acute respiratory
distress syndrome (ARDS). The study is expected to enroll
approximately 270 patients across countries with high numbers of
diagnosed cases, beginning in May, and will evaluate the impact of
ULTOMIRIS, a biologic medicine, on survival, duration of mechanical
ventilation, and hospital stay compared to best supportive care.
This follows the U.S. Food and Drug Administration’s (FDA) rapid
review and acceptance of Alexion’s investigational new drug (IND)
application for ULTOMIRIS for severe COVID-19.
“Alexion has been in close contact with physicians and global
health authorities in an effort to rapidly evaluate the potential
of C5 inhibition in treating patients with severe COVID-19,” said
John Orloff, M.D., Executive Vice President and Head of Research
& Development at Alexion. “Based on early anecdotal information
available from compassionate use cases in multiple countries, we
are launching a controlled clinical trial to evaluate the potential
of ULTOMIRIS in mitigating the severe pneumonia and lung injury
caused by the virus. As we move quickly to initiate this program,
we also remain committed to serving the patients who currently rely
on our medicines and providing continuous supply to these
patients.”
The decision to begin this trial is based on a) published
preclinical data suggesting that inhibition of terminal complement
can lower cytokine and chemokine levels and significantly reduce
lung inflammation and pathology in animal models of viral
pneumoniai, and b) elevated complement biomarkers and promising
preliminary clinical evidence from patients who have accessed
SOLIRIS® (eculizumab) through our compassionate use program, which
suggests that complement inhibition may improve
coronaviral-mediated lung injury.
Independent investigators have expressed interest in studying
the potential of C5 inhibition in severe COVID-19 pneumonia, and we
are aware of several ongoing or planned independent studies and
anecdotal results from the use of our C5 inhibitors in patients
with COVID-19. While these healthcare professionals continue to
aggregate data regarding the potential of terminal complement
inhibition in COVID-19 pneumonia from the approximately 100
patients who have been treated so far, Alexion believes that the
outcomes reported to date warrant conducting a controlled clinical
program to explore the impact of C5 inhibition with ULTOMIRIS and
establish clinical evidence supporting the role of terminal
complement in coronaviral pneumonia. We believe ULTOMIRIS
represents the future of C5 inhibition, with its weight-based
dosing, reduced burden on hospital systems due to less frequent
dosing and it can be manufactured at a higher capacity, providing
the opportunity to better meet future supply demands.
For additional information on Alexion’s ongoing efforts related
to COVID-19, please visit:
https://alexion.com/our-commitment/covid-19.
About the Phase 3 Study
The Phase 3 open-label, randomized, controlled study is designed
to evaluate the safety and efficacy of ULTOMIRIS in approximately
270 adults hospitalized with COVID-19 and severe pneumonia, acute
lung injury or acute respiratory distress syndrome (ARDS). Study
participants will be randomized 2:1 to receive ULTOMIRIS or best
supportive care. The primary endpoint is survival at Day 29.
Secondary endpoints will assess the need for mechanical
ventilation, oxygenation, duration of ICU stay and hospitalization,
and safety, among others.
Patients in the ULTOMIRIS arm will receive a weight-based
loading dose of ULTOMIRIS on Day 1 (2400mg for patients weighing
40-60kg, 2700mg for 60-100kg, or 3000mg for ≥100kg). Follow-up
dosing on Days 5, 10 and 15 will also be weight-based; patients
weighing 40 to 60kg will receive 600mg of ULTOMIRIS and patients
weighing 60kg or more will receive 900mg of ULTOMIRIS. All patients
will continue to receive medications, therapies, and interventions
per standard hospital treatment protocols for the duration of the
study. Following the 4-week treatment period, there will be safety
follow-up monitoring for three months.
Expanded Access Programs
In recognition of the urgent needs of some patients and in order
to streamline the emergency access process, Alexion has opened
emergency Expanded Access Programs (EAP) in the U.S. and France for
SOLIRIS in severe COVID-19 pneumonia. All requests for a hospital
to be included in the EAP must be made by a treating physician and
can be submitted to covid.requests@alexion.com.
Access & Supply Considerations
Alexion’s focus has always been on developing transformative
medicines for patients with rare and ultra-rare diseases that
typically affect several hundred to a few thousand patients
worldwide. Like all of our medicines, ULTOMIRIS is a biologic
medicine, which are very large complex molecules made up of
genetically engineered proteins that are manufactured in living
cells through a highly complicated process that requires
significant time, expertise and precision. During this global
health crisis, we have taken proactive measures that are designed
to mitigate the risk of potential supply interruptions, and we
strive to maintain sufficient inventory levels to continue serving
current and new patients receiving our medicines for approved rare
and ultra-rare indications as well as those participating in
ongoing clinical trials.
We recognize that, should the role of C5 in treating severe
respiratory complications of COVID-19 be demonstrated in a
controlled clinical trial, there is the potential for significantly
increased demand for our C5 inhibitors. We have taken steps to
significantly increase future supply as part of our efforts to
prepare for this and other potential scenarios that may arise so
that we are ready to support access and the anticipated increased
supply demand. In the meantime, Alexion will continue to monitor
and manage the production of ULTOMIRIS, appropriately taking into
consideration the needs of current and new patients, required
inventory levels, anticipated potential supply needs related to
COVID-19 and the time-intensive and complex manufacturing process
to produce monoclonal antibodies while maintaining the company’s
rigorous quality standards.
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. For currently approved indications, 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.
INDICATIONS & IMPORTANT SAFETY INFORMATION FOR ULTOMIRIS®
(ravulizumab-cwvz) AND SOLIRIS® (eculizumab)
INDICATIONS
ULTOMIRIS and SOLIRIS are prescription medicines called
monoclonal antibodies. ULTOMIRIS and SOLIRIS are used to treat
adults with a disease called Paroxysmal Nocturnal Hemoglobinuria
(PNH). ULTOMIRIS and SOLIRIS are also used to treat adults and
children with a disease called atypical Hemolytic Uremic Syndrome
(aHUS). Neither ULTOMIRIS nor SOLIRIS is for use in treating people
with Shiga toxin E. coli related hemolytic uremic syndrome
(STEC-HUS).
In addition, SOLIRIS is used to treat adults with a disease
called generalized myasthenia gravis (gMG) who are
anti-acetylcholine receptor (AChR) antibody positive. SOLIRIS is
also used to treat adults with a disease called neuromyelitis
optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4)
antibody positive.
It is not known if ULTOMIRIS is safe and effective in children
with PNH or in children younger than one month of age in aHUS. It
is also not known if SOLIRIS is safe and effective in children with
PNH, gMG, or NMOSD.
IMPORTANT SAFETY INFORMATION
ULTOMIRIS and SOLIRIS are medicines that affect the immune
system. These medicines can lower the ability of the immune system
to fight infections. Both medicines increase 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 two weeks
before the first dose of ULTOMIRIS or SOLIRIS if the patient has
not already had this vaccine. If the patient’s doctor decided that
urgent treatment is needed, meningococcal vaccination should be
administered as soon as possible. If the patient has not been
vaccinated and therapy must be initiated immediately, two weeks of
antibiotics should also be administered with the vaccinations. If
the patient had a meningococcal vaccine in the past, additional
vaccination might be needed before starting ULTOMIRIS or SOLIRIS.
Patients should ask their doctor if an additional meningococcal
vaccination is needed. Meningococcal vaccines reduce the risk of
meningococcal infection but do not prevent all meningococcal
infections. Patients should be instructed to call their 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. The doctor will
provide a Patient Safety Card about the risk of meningococcal
infection. This card must be carried at all times during treatment
and for 8 months after the last ULTOMORIS dose or 3 months after
the last SOLIRIS dose.
Before a patient can receive ULTOMIRIS or SOLIRIS, their doctor
must: enroll in the corresponding ULTOMIRIS REMS or SOLIRIS REMS
program; counsel the patient about the risk of meningococcal
infection; give the patient information and a Patient Safety Card
about the symptoms and risk of meningococcal infection (as
discussed above); and make sure that the patient is vaccinated with
a meningococcal vaccine.
ULTOMIRIS and SOLIRIS may also increase the risk of other types
of serious infections. Patients should talk to their doctor right
away if they have any new signs or symptoms of infection.
Patients must not receive ULTOMIRIS or SOLIRIS if they have a
meningococcal infection, or if they have not been vaccinated
against meningococcal infection, unless their doctor decides that
urgent treatment is needed.
Before a patient receives ULTOMIRIS or SOLIRIS, they should tell
their doctor about all of their medical conditions, including if
they: 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 or SOLIRIS will harm an unborn baby or if these
medicines pass into the breast milk.
Patients should tell their doctor about all the medicines they
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements. ULTOMIRIS and SOLIRIS can affect
how other medicines work, causing side effects.
For patients with PNH, the doctor will need to monitor the
patient closely for at least 16 weeks after stopping ULTOMIRIS or 8
weeks after stopping SOLIRIS. Stopping treatment with these
medicines may cause breakdown of the red blood cells due to PNH.
Symptoms or problems that can happen due to red blood cell
breakdown include: a drop in 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.
For patients with aHUS, the doctor will need to monitor closely
during and for at least 12 months after stopping ULTOMIRIS, or 12
weeks after stopping SOLIRIS, for signs of worsening aHUS symptoms
or problems related to abnormal clotting and breakdown of 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 infusion
reactions. 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. Patients should tell their doctor
or nurse right away if they develop these symptoms, or any other
symptoms during their ULTOMIRIS infusion that may mean they are
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.
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
infection, diarrhea, nausea, vomiting, headache, high blood
pressure and fever.
SOLIRIS can cause serious side effects including serious
allergic reactions. Serious allergic reactions can happen during
the SOLIRIS infusion. Patients should tell their doctor or nurse
right away if they get 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 a patient 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. The most
common side effects in people with NMOSD treated with SOLIRIS
include: common cold (upper respiratory infection); pain or
swelling of the 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
ULTOMIRIS or SOLIRIS. For more information, ask your doctor or
pharmacist. Call your doctor right away if you miss an ULTOMIRIS or
SOLIRIS infusion or for medical advice about side effects. You may
report side effects to FDA at 1-800-FDA-1088.
Please refer to the full U.S. Prescribing Information and
Medication Guide for ULTOMIRIS and SOLIRIS available via the links
below, including the BOXED WARNING regarding serious and
life-threatening meningococcal infections for both medicines.
ULTOMIRIS Full Prescribing Information and Medication
Guide
SOLIRIS Full Prescribing Information and Medication
Guide
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
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:
future plans for a clinical trial of ULTOMIRIS for approximately
270 adults with COVID-19 who are hospitalized with severe pneumonia
or acute respiratory distress syndrome; the timing of the
commencement, conclusion and reporting of results of such clinical
trial; we are attempting to rapidly evaluate the potential of C5
inhibition in treating patients with severe COVID-19; Alexion will
maintain and commits to continue to supply its medicines to current
and future patients for approved indications; complement inhibition
may improve coronaviral-mediated lung injury; Alexion believes
ULTOMIRIS represents the future of C5 inhibition, and it may reduce
the burden on hospital systems with less frequent dosing and can be
manufactured at a higher capacity, providing the opportunity to
better meet future supply demands; Alexion will strive to maintain
sufficient inventory levels to continue serving current and new
patients receiving our medicines for approved indications as well
as those participating in ongoing clinical trials; should the role
of C5 in treating severe respiratory complications of COVID-19 be
demonstrated in a controlled clinical trial, there is the potential
for significantly increased demand for our C5 inhibitors; Alexion
is working to prepare for potential increased demand and other
potential scenarios that may arise so that we are ready to support
access; Alexion will continue to monitor and manage the production
of ULTOMIRIS, appropriately taking into consideration the needs of
current and new patients, required inventory levels, anticipated
potential supply needs related to COVID-19 and the time-intensive
and complex manufacturing process to produce monoclonal antibodies
while maintaining the company’s rigorous quality standards; the
Company is prepared to support the appropriate government agencies
in their efforts to address the public health crisis caused by the
COVID-19 pandemic, and to leverage our expertise in complement
biology to the extent it may help address this novel threat;
ULTOMIRIS may have a positive impact in mitigating the certain harm
and injury caused by COVID-19; and the Company believes that the
outcomes reported to-date warrant conducting a controlled clinical
program to explore the impact of C5 inhibition with ULTOMIRIS and
establish clinical evidence supporting the role of terminal
complement in coronaviral pneumonia. 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: SOLIRIS and/or ULTOMIRIS may not
have any beneficial impact on any patients with COVID-19; ULTOMIRIS
may not be a safe and/or effective treatment for any patients with
COVID-19; the risks of ULTOMIRIS as a treatment for patients with
COVID-19 may exceed any benefits of the therapy; the FDA (and any
other regulatory agency) may not approve ULTOMIRIS as a treatment
for COVID-19 or a subset of patients with COVID-19; any potential
regulatory approval of ULTOMIRIS as a treatment for COVID-19, even
if obtained, may be delayed; there may be competing therapies for
COVID-19 and ULTOMIRIS may not gain market acceptance; the
anticipated benefits of ULTOMIRIS for any COVID-19 patients may not
be realized (and the results of the clinical trials may not be
indicative of the results once approved for use in a broader
population); results of clinical trials may not be sufficient to
satisfy the FDA or any other regulatory authority in order to
approve ULTOMIRIS as a treatment for COVID-19 patients (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
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); unexpected delays in
clinical trials (including due to capacity constraints at trial
sites due to COVID-19); 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; inability to meet expected demand for
our products due to manufacturing issues (at Alexion or at third
parties), supply chain issues or otherwise; our manufacturing and
third-party manufacturing may not be sufficient to meet product
demand for ULTOMIRIS (including due to manufacturing employee
exposure to COVID-19); we may not be able to maintain sufficient
inventory of product; we may be unable to deliver our products (due
to transportation interruption as a result of COVID-19); 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 C5 inhibitor products; 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 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 the FDA and other regulatory agencies regarding products
and product candidates; 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 and inter partes review petitions submitted 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 (SEC) and U.S.
Department of Justice; the risk that estimates regarding the number
of patients with PNH, aHUS, gMG, NMOSD, HPP, COVID-19 and LAL-D and
other indications we are pursuing are inaccurate; the risks of
changing foreign exchange rates; 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
Annual Report on Form 10-K for the year ended December 31, 2019 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.
__________
i Gralinski LE, Sheahan TP, Morrison TE,
et al. Complement activation contributes to severe acute
respiratory syndrome coronavirus pathogenesis. mBio. 2018;9(5).
doi:10.1128/mBio.01753-18.
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Alexion Contacts: Media Megan Goulart,
857-338-8634 Senior Director, Corporate Communications
Investors Chris Stevo, 857-338-9309 Head of Investor
Relations
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