- CHMP Recommends Marketing Authorization for
Strensiq for Patients with Pediatric-Onset HPP -
- CHMP Recommends Marketing Authorization for
Kanuma for Patients of all Ages with LAL-d -
Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) announced today that
the Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) has adopted positive opinions
recommending marketing authorization of Strensiq™ (asfotase alfa)
and Kanuma™ (sebelipase alfa). The proposed indication for Strensiq
is for long-term enzyme replacement therapy in patients with
pediatric-onset hypophosphatasia (HPP) to treat the bone
manifestations of the disease. The proposed indication for Kanuma
is for long-term enzyme replacement therapy in patients of all ages
with lysosomal acid lipase deficiency (LAL-d). Based on the CHMP’s
positive recommendations, final decisions from the European
Commission are expected in the third quarter of 2015, after which
the Company will begin the country-by-country reimbursement
processes. Currently, there are no therapies approved for the
treatment of HPP or LAL-d.
“The CHMP positive opinions for Strensiq and Kanuma are
significant milestones in bringing these therapies to infants,
children, and adults suffering from HPP and LAL-d in Europe,” said
David Hallal, Chief Executive Officer of Alexion. “Both Strensiq
and Kanuma are highly innovative enzyme replacement therapies that,
if approved, will be the first treatments available for patients
with HPP and LAL-d, two life-threatening and ultra-rare metabolic
disorders.”
HPP is a genetic, progressive, ultra-rare metabolic disease in
which patients experience devastating effects on multiple systems
of the body, leading to debilitating or life-threatening
complications. It is characterized by defective bone mineralization
that can lead to deformity of bones and other skeletal
abnormalities, as well as systemic complications such as profound
muscle weakness, seizures, pain and respiratory failure leading to
premature death in infants.1-5
LAL-d is a genetic, progressive, ultra-rare metabolic disease in
which patients ranging from infants to adults experience chronic
lipid accumulation causing multi-systemic organ damage and
premature death. It is caused by genetic mutations that result in
decreased LAL enzyme activity in the lysosomes across multiple body
tissues, leading to the chronic build-up of fatty material in the
liver, blood vessel walls and other tissues.6
Strensiq CHMP Opinion
The proposed indication for Strensiq is for long-term enzyme
replacement therapy in patients with pediatric-onset HPP to treat
the bone manifestations of the disease. HPP is associated with
multiple bone manifestations including rickets/osteomalacia,
altered calcium and phosphate metabolism, impaired growth and
mobility, respiratory compromise that may require ventilation, and
vitamin B6-responsive seizures. The natural history of untreated
infant hypophosphatasia patients suggests high mortality if
ventilation is required. In clinical trials, 71% of infant patients
treated with Strensiq who required ventilation support remain alive
and continue on treatment.
As noted in the CHMP Summary of Opinion, the benefit of exposure
to Strensiq is an improvement in skeletal structure, as
demonstrated by x-ray appearance of joints, by histological
appearance of bone biopsy material, and by apparent catch-up
height-gain. The CHMP based its opinion on clinical data from 68
patients with pediatric-onset HPP (ranging from newborns to 66
years of age) enrolled in three pivotal prospective studies and
their extensions.
“The CHMP positive opinion brings Strensiq one step closer to
the HPP community, which currently has no approved option to treat
the disease,” said Professor Zulf Mughal, Royal Manchester
Children's Hospital, UK. “In clinical studies, treatment with
Strensiq was associated with rapid and sustained improvements in
bone mineralization, mobility and growth in patients with
pediatric-onset HPP.”
The most common adverse reactions observed were injection site
reactions and injection-associated adverse reactions. Most of these
reactions were non-serious, mild to moderate in intensity. A
summary of the CHMP opinion for Strensiq can be accessed at
http://www.emea.europa.eu.
Kanuma CHMP Opinion
The proposed indication for Kanuma is for long-term enzyme
replacement therapy in patients of all ages with LAL-d. As noted in
the CHMP Summary of Opinion, the benefits of Kanuma are its ability
to replace the activity of the missing enzyme resulting in reduced
liver fat content and reduced levels of blood transaminases,
low-density lipoprotein (LDL) cholesterol, non-high-density
lipoprotein (HDL) and triglycerides. In addition, there was a
significant benefit in terms of survival (67%) in patients with the
infant form of LAL-d beyond 12 months.
The CHMP reviewed Kanuma under accelerated assessment. The CHMP
based its opinion on clinical data from four clinical studies in
which 84 patients with LAL-d (including infants, children, and
adults) were treated with Kanuma.
“In clinical studies, treatment with Kanuma significantly
improved overall survival in infants and led to normalization of
ALT and other markers of liver injury in pediatric and adult
patients compared to placebo. Kanuma was also associated with
marked improvements in other disease-related parameters of
dyslipidemia and liver injury, including decreased liver fat
content, in adult and pediatric patients with LAL-d,” said Vassili
Valayannopoulos, M.D., Ph.D., Principal Investigator at Hôpital
Necker-Enfants Malades and IMAGINE Institute, Paris. “Today’s
positive CHMP opinion is an extremely important step for patients
with LAL-d, who currently are at risk for multi-systemic organ
damage and premature death in the absence of an effective
therapy.”
The most serious adverse reactions experienced by 3% of patients
in clinical trials were signs and symptoms consistent with
anaphylaxis. Signs and symptoms included chest discomfort,
conjunctival injection, dyspnea, generalized and itchy rash,
hyperemia, mild eyelid edema, rhinorrhea, severe respiratory
distress, tachycardia, tachypnea and urticaria. A summary of the
CHMP opinion for Kanuma can be accessed at
http://www.emea.europa.eu.
About Hypophosphatasia (HPP)
HPP is a genetic, chronic and progressive ultra-rare metabolic
disease characterized by defective bone mineralization that can
lead to deformity of bones and other skeletal abnormalities, as
well as systemic complications such as profound muscle weakness,
seizure, and respiratory failure leading to premature death.1-5
HPP results from a mutation in the gene that makes an enzyme
known as tissue non-specific alkaline phosphatase (TNSALP).1,2 The
genetic deficiency in HPP can affect people of all ages.1 HPP is
classified by the age of the patient at the onset of symptoms of
the disease, with infantile- and juvenile-onset HPP defined as
manifestation of the first symptom prior to 18 years of age.
HPP can have devastating consequences for patients at any stage
of life.1 In a natural history study, infants who had their first
symptom of HPP within the first 6 months of life had high
mortality, with an overall mortality rate of 73% at 5 years.7 In
these patients, mortality is primarily due to respiratory
failure.1,2,8 In patients surviving to adolescence and adulthood,
long-term clinical sequelae can include recurrent and non-healing
fractures, muscle weakness, pain and the requirement for ambulatory
assistive devices such as wheelchairs, wheeled walkers and
canes.1,4
About Lysosomal Acid Lipase Deficiency (LAL Deficiency or
LAL-d)
LAL-d is a serious, life-threatening disease associated with
early mortality and significant morbidity. LAL-d is a chronic
disease in which genetic mutations result in decreased activity of
the LAL enzyme. This leads to marked accumulation of lipids in
vital organs, blood vessels, and other tissues, resulting in
progressive and multi-systemic organ damage including fibrosis,
cirrhosis, liver failure, accelerated atherosclerosis,
cardiovascular disease, and other devastating consequences.6,9
LAL-d affects patients of all ages with sudden and unpredictable
clinical complications manifesting from infancy through adulthood.
Infants experience profound growth failure, liver fibrosis,
cirrhosis and death at a median age of death 3.7 months.10 In a
natural history study, approximately 50% of children and adults
with LAL-d progressed to fibrosis, cirrhosis, liver transplant or
death in 3 years.11 The median age of onset of LAL-d is 5.8 years
and the disease can be diagnosed with a simple blood test.12,13
About Strensiq™ (asfotase alfa)
Strensiq™ (asfotase alfa) is a first-in-class enzyme replacement
therapy designed to address the underlying cause of HPP—deficient
alkaline phosphatase (ALP). By replacing deficient ALP, treatment
with Strensiq aims to improve the elevated enzyme substrate levels
and improve the body's ability to mineralize bone, thereby
preventing serious skeletal and systemic patient morbidity and
premature death.
The FDA granted Breakthrough Therapy designation for Strensiq
and accepted Alexion’s Biologics License Application (BLA) for
Priority Review. Alexion has also submitted a New Drug Application
for Strensiq to Japan’s Ministry of Health, Labour and Welfare
(MHLW).
About Kanuma™ (sebelipase alfa)
Kanuma™ (sebelipase alfa) is a recombinant form of the
human LAL enzyme designed to address the root cause of lysosomal
acid lipase deficiency (LAL-d). By replacing deficient LAL,
treatment with Kanuma aims to reduce substrate accumulation and
improve lipid metabolism, which can prevent chronic lipid
accumulation, multi-systemic organ damage and premature death.
The FDA granted Breakthrough Therapy designation for Kanuma for
LAL Deficiency presenting in infants and accepted the Kanuma BLA
for Priority Review. In addition, a New Drug Application for Kanuma
was submitted to Japan’s MHLW.
About Alexion
Alexion is a global biopharmaceutical company focused on
developing and delivering life-transforming therapies for patients
with devastating and rare disorders. Alexion developed and
commercializes Soliris® (eculizumab), the first and only approved
complement inhibitor to treat patients with paroxysmal nocturnal
hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS),
two life-threatening ultra-rare disorders. Alexion is also
establishing a premier global metabolic rare disease franchise with
the development of two late-stage therapies, Strensiq™ (asfotase
alfa) for hypophosphatasia (HPP) and Kanuma™ (sebelipase alfa) for
Lysosomal Acid Lipase Deficiency (LAL-d). In addition, Alexion is
advancing the most robust rare disease pipeline in the biotech
industry, with highly innovative product candidates in multiple
therapeutic areas. As the global leader in complement inhibition,
the Company is strengthening and broadening its portfolio of
complement inhibitors across diverse platforms, including
evaluating potential indications for Soliris in additional severe
and ultra-rare disorders. This press release and further
information about Alexion can be found at: www.alexion.com.
[ALXN-G]
Forward-Looking Statements
This news release contains forward-looking statements, including
statements related to potential medical benefits of Strensiq™
(asfotase alfa) for hypophosphatasia (HPP) and Kanuma™ (sebelipase
alfa) for lysosomal acid lipase deficiency (LAL Deficiency).
Forward-looking statements are subject to factors that may cause
Alexion's results and plans to differ from those expected,
including, for example, decisions of regulatory authorities
regarding marketing approval or material limitations on the
marketing of Strensiq for HPP and Kanuma for LAL Deficiency, delays
in arranging satisfactory manufacturing capabilities and
establishing commercial infrastructure for Strensiq for HPP or
Kanuma for LAL Deficiency, the possibility that results of clinical
trials are not predictive of safety and efficacy results of
Strensiq or Kanuma in broader or different patient populations, the
risk that third party payors (including governmental agencies) will
not reimburse for the use of Strensiq or Kanuma (if approved) at
acceptable rates or at all, the risk that estimates regarding the
number of patients with Strensiq or Kanuma and observations
regarding the natural history of patients with Strensiq or Kanuma
are inaccurate, and a variety of other risks set forth from time to
time in Alexion's filings with the Securities and Exchange
Commission, including but not limited to the risks discussed in
Alexion's Quarterly Report on Form 10-Q for the period ended March
31, 2015 filed on April 24, 2015, and in the Quarterly Report on
Form 10-Q for the period ended March 31, 2015 filed by Alexion's
subsidiary, formerly known as Synageva BioPharma Corp., on April
30, 2015. Alexion does not intend 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. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol
Rev. 2013; 10(suppl 2):380-388.
2. Whyte MP. Hypophosphatasia: nature’s window on alkaline
phosphatase function in humans. In: Bilezikian JP, Raisz LG, Martin
TJ, eds. Principles of Bone Biology. Vol 1. 3rd ed. San Diego, CA:
Academic Press; 2008:1573-1598.
3. Whyte MP, Greenberg CR, Salman N, et al. Enzyme-replacement
therapy in life-threatening hypophosphatasia. N Engl J Med. 2012;
366(10):904-913.
4. Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy
with hypophosphatasia. Arch Dis Child. 1990; 65(1):130-131.
5. Baumgartner-Sigl S, Haberlandt E, Mumm S, et al.
Pyridoxine-responsive seizures as the first symptom of infantile
hypophosphatasia caused by two novel missense mutations
(c.677T>C, p.M226T; c.1112C>T, p.T371I) of the
tissue-nonspecific alkaline phosphatase gene. Bone. 2007;
40(6):1655-1661.
6. Berstein DL, et al. Chloesteryl ester storage disease: review
of the findings in 135 reported patients with an underdiagnosed
disease. J Hepatol. 2013;58:1230-43.
doi:10.1016/j.jhep.2013.02.014.
7. Whyte MP, Leung E, Wilcox W, et al. Hypophosphatasia: a
retrospective natural history study of the severe perinatal and
infantile forms. Poster presented at the 2014 Pediatric Academic
Societies and Asian Society for Pediatric Research Joint Meeting,
Vancouver, B.C., Canada, May 5, 2014. Abstract 752416.
8. Whyte MP, Rockman-Greenberg C, Hofmann C, et al. Improved
survival with asfotase alfa treatment in pediatric patients with
hypophosphatasia at high risk of death. Poster presented at the
American Society for Bone and Mineral Research (ASBMR) 2014 Annual
Meeting, Houston, September 14, 2014. Abstract 1097.
9. Reiner Z, et al. Lysosomal acid lipase deficiency – an
under-recognized cause of dyslipidemia and liver dysfunction.
Atherosclerosis. 2014;235:21-30.
doi:10.1016/j.atherosclerosis.2014.04.003.
10. Jones S, et al. Poster presented at: Lysosomal Disease
Network WORLD Symposium; February, 2014
11. Data on file. Based on modelling using the subset of 31
patients (≥ 5 years) in Natural History Study LAL2-NH01 who had a
liver biopsy performed during their medical care plus 1 patient
without a biopsy who received a liver transplant; An important
source of selection bias in this analysis is that patients who were
selected by their clinician for liver biopsy would be expected to
have more evidence of disease progression than the overall
population of patients with CESD
12. Quinn, A. et al. WORLD Symposium, February, 2014
13. Hamilton J, et al. A new method for the measurement of
lysosomal acid lipase in dried blood spots using the inhibitor
Lalistat 2. Clin Chim Acta. 2012;413:1207-10.
doi:10.1016/j.cca.2012.03.019.
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Alexion:MediaIrving Adler, 203-271-8210Vice President,
Corporate CommunicationsorKim Diamond, 203-439-9600Executive
Director, Corporate CommunicationsorInvestorsElena Ridloff, CFA,
203-699-7722Executive Director, Investor Relations
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