- Physicians in Japan will soon be able to
prescribe a treatment for PNH that requires fewer infusions,
reducing the treatment burden for patients -
- ULTOMIRIS has the potential to become the new
standard of care for both complement inhibitor-naïve patients and
patients switching from SOLIRIS® (eculizumab) -
Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today
announced that Japan’s Ministry of Health, Labour and Welfare
(MHLW) has approved ULTOMIRIS® (ravulizumab), the first and only
long-acting C5 complement inhibitor administered every eight weeks,
for the treatment of adult patients with paroxysmal nocturnal
hemoglobinuria (PNH).
PNH is an ultra-rare and severe disease that, when left
untreated, may cause a wide range of debilitating symptoms and
complications, including thrombosis. Thrombosis occurs when a blood
clot presents inside a blood vessel, and slows or blocks the flow
of blood through the circulatory system. Serious cases of
thrombosis can occur throughout the body and result in organ
damage, stroke, heart attack, and potentially premature
death.1–8
“As a physician, I am pleased to have a new medication for
patients in Japan facing the burden of living with PNH—both for
people naive to anti-complement therapy and those that are already
on SOLIRIS seeking to make a change without interruption,” said
Jun-ichi Nishimura, M.D., Ph.D. Assistant Professor, Department of
Hematology and Oncology, Osaka University Graduate School of
Medicine, Japan. “When PNH is not treated, the consequences can be
serious.”
PNH can strike men and women of all races, backgrounds and ages
without warning, with an average age of onset in the early 30s.1,9
PNH often goes unrecognized, with delays in diagnosis ranging from
one to more than five years.10
The Ministry’s approval is based on comprehensive results from
two Phase 3 studies, which were published in Blood.11,12 In these
studies, which included 441 patients who had either never been
treated with a complement inhibitor before, or who had been stable
on SOLIRIS, the efficacy of ULTOMIRIS administered every eight
weeks was non-inferior to the efficacy of SOLIRIS administered
every two weeks on all 11 endpoints. The safety profile of
ULTOMIRIS was similar to that of SOLIRIS. Additional data showed
that ULTOMIRIS provided immediate and complete C5 inhibition that
was sustained for eight weeks13 and that ULTOMIRIS eliminated
breakthrough hemolysis associated with incomplete C5 inhibition.14
The entire clinical development program for ULTOMIRIS to date
represents more than 800 patient years of experience.
“Immediate and complete C5 inhibition with ULTOMIRIS can provide
meaningful benefits for patients and their families,” said John
Orloff, M.D., Executive Vice President and Head of Research &
Development at Alexion. “Based on the totality of our compelling
data from the largest Phase 3 program ever conducted in PNH, we
believe ULTOMIRIS has the potential to become the new standard of
care for patients with PNH in Japan. We would like to express our
deep gratitude to the patients and investigators in Japan who
supported this study with their participation.”
About Paroxysmal Nocturnal Hemoglobinuria (PNH)Paroxysmal
nocturnal hemoglobinuria (PNH) is a chronic, progressive,
debilitating and life-threatening ultra-rare blood disorder
characterized by hemolysis (destruction of red blood cells) that is
mediated by an uncontrolled activation of the complement system, a
component of the body’s immune system.1,2,15 PNH can strike men and
women of all races, backgrounds and ages without warning, with an
average age of onset in the early 30s.1,9 PNH often goes
unrecognized, with delays in diagnosis ranging from one to more
than five years.10 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.3–5,7,8,11,15 The most devastating
consequence of chronic hemolysis is thrombosis, which can occur in
blood vessels throughout the body, damage vital organs and cause
premature death.16 The first thrombotic event can be fatal.1,9,17
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.18,19 Patients with
certain types of hemolytic anemia, bone marrow disorders and
unexplained venous or arterial thrombosis are at increased risk of
PNH.15,20–24
About ULTOMIRIS®ULTOMIRIS (ravulizumab), the first
and only long-acting C5 inhibitor administered every eight weeks,
is approved in the U.S. and Japan 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). In Phase 3 clinical studies in complement inhibitor-naïve
patients with PNH11 and patients with PNH who had been stable on
SOLIRIS® (eculizumab),12 intravenous treatment with ULTOMIRIS every
eight weeks demonstrated non-inferiority to intravenous treatment
with SOLIRIS every two weeks on all 11 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, aHUS and gMG.
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®
(ravulizumab-cwvz)ULTOMIRIS 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®
(ravulizumab-cwvz)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. 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. Important Safety Information for SOLIRIS®
(eculizumab)SOLIRIS 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 AlexionAlexion 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). 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 second complement
inhibitor, a copper-binding agent for Wilson disease and an
anti-neonatal Fc receptor (FcRn) antibody for rare Immunoglobulin G
(IgG)-mediated diseases as well as several early-stage therapies,
including one for light chain (AL) amyloidosis and a second
anti-FcRn therapy. 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, and metabolic disorders. Alexion has been named to the
Forbes list of the World’s Most Innovative Companies seven years in
a row and is headquartered in Boston, Massachusetts’ Innovation
District. The company also 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 StatementsThis presentation contains
forward-looking statements, including statements related to: the
belief that ULTOMIRIS has the potential to become the new standard
of care for patients with PNH (including those in PNH patients in
Japan); the Company’s plans to make future regulatory filings for
approval of certain products and product candidates and the timing
of such filings, including applications for approval of ULTOMIRIS
in the EU and Japan later in 2019 for patients with aHUS; ULTOMIRIS
intravenously administered every eight weeks is a potential
treatment for patients with gMG; the Company’s plans for future
clinical trials and studies (including plans to initiate a Phase 3
trial in patients with NMOSD), the timing for the commencement of
future clinical trials and the expected timing of the receipt of
results of certain clinical trials and studies; ULTOMIRIS
subcutaneously administered once per week is a potential treatment
for patients with PNH, aHUS and gMG; and the potential benefits of
current products and products under development and in clinical
trials (including ULTOMIRIS as a treatment for patients with PNH).
Forward-looking statements are subject to factors that may cause
Alexion's results and plans to differ materially from those
forward-looking statements, including for example: any potential
post-approval restrictions that the MHLW or any other regulatory
agency may impose on Ultomiris; Ultomiris and other products and
product candidates do not gain regulatory approval from the MHLW,
FDA, EMA or other regulatory authorities; 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; our products, including ULTOMIRIS do not gain
acceptance among patients and/or physicians and do not become the
standard of care for certain indications; 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); our inability to facilitate the timely conversion of PNH
patients (and any future indications) from Soliris to Ultomiris;
payer, physician and patient acceptance of Ultomiris as an
alternative to Soliris; appropriate pricing for Ultomiris; future
competition from biosimilars and novel products (and such future
competition causes ULTOMIRIS not to be the standard of care for
certain indications); 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, increased 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 MHLW, FDA and other regulatory agencies regarding
products and product candidates; results in early stage clinical
trials may not be indicative of full results or results from later
stage or larger clinical trials (or in broader patient populations)
and do not ensure regulatory approval; 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 halt trials,
discontinue sales of our products, delay or prevent us from making
regulatory approval filings or result in denial of approval of our
product candidates; 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 following commercialization); future product
improvements may not be realized due to expense or feasibility or
other factors; 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; 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; 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, HPP
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
Quarterly Report on Form 10-Q for the quarter ended March 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.
References
1. Hill A, Richards SJ, Hillmen P. Br J Haematol. 2007
May;137(3):181-92.
2. Hillmen P, Lewis SM, Bessler M, et al. N Engl J Med. 1995 Nov
9;333(19):1253-8.
3. Schrezenmeier H, Muus P, Socié G, et al. Haematologica.
2014;99:922-929.
4. Brodsky RA. Blood Rev. 2008;22:65-74.
5. Weitz I, Meyers G, Lamy T, et al. Intern Med J.
2013;43:298-307.
6. Lee JW, Jang JH, Kim JS, et al. Int J Hematol.
2013;97:749-757.
7. Dacie JV, Lewis SM. Ser Haemat. 1972;5:3-23.
8. Nishimura J, Kanakura Y, Ware RE, et al. Medicine (Baltimore)
2004 May;83(3):193-207.
9. Socié G, Mary JY, de Gramont A, et al. Lancet.
1996;348:573-577.
10. Shammo JM, Mitchell RL, Ogborn K et al. Blood.
2015;126:3264.
11. Lee JW, Sicre de Fontbrune F, Lee LWL et al. [published
online ahead of print, December 3, 2018].
Blood.doi:10.1182/blood-2018-09-876136.
12. Kulasekararaj AG, Hill A, Rottinghaus ST et al. [published
online ahead of print December 3, 2018]. Blood.
doi:10.1182/blood-2018-09-876805.
13. Peffault de Latour R, Brodsky RA, Ortiz S et al. American
Society of Hematology (ASH) Annual Meeting, San Diego, December 2,
2018;Session 101:2330.
14. Brodsky RA, Peffault de Latour R, Rottinghaus ST et al.
American Society of Hematology (ASH) Annual Meeting, San Diego,
December 3, 2018;Session 101:626.
15. Parker C, Omine M, Richards S, et al. Blood. 2005
Dec;106(12):3699-3709.
16. Hillmen P, Muus P, Duhrsen U, et al. Blood. 2007
Dec;110(12):4123-8.
17. Hillmen P, Elebute MO, Kelly R, et al. Blood. 2007;110:
Abstract 3678.
18. Hillmen P, Muus P, R�th A, et al. Br J Haematol.
2013;162:62-73.
19. Loschi M, Porcher R, Barraco F, et al. Am J Hematol.
2016;91:366-370.
20. Borowitz MJ, Craig FE, DiGiuseppe JA, et al. Cytometry B
Clin Cytom. 2010;78B:211-230.
21. Rachidi S, Musallam KM, Taher AT. Eur J Intern Med.
2010;21:260-267.
22. Morado M, Freire Sanders A, Colado E et al. Cytometry Part B
(Clinical Cytometry). 2017;92B:361-370.
23. Hill A, Kelly RJ, Hillmen P. Blood. 2013;121:4985-4996.
24. Sharma VR. Clin Adv Hematol Oncol. 2013;11(suppl
13):1-11.
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Alexion Pharmaceuticals, Inc.MediaElizabeth Kalina,
617-862-7072Head Portfolio, Country and Internal
CommunicationsMegan Goulart, 857-338-8634Senior Director, Corporate
CommunicationsInvestorsSusan Altschuller, PhD, 857-338-8788
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