Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) today announced that it has
submitted a New Drug Application (NDA) for asfotase alfa, an
investigational, first-in-class targeted enzyme replacement therapy for
the treatment of hypophosphatasia (HPP), to Japan’s Ministry of Health,
Labour and Welfare (MHLW). HPP is a genetic, chronic and progressive
ultra-rare metabolic disease that can lead to destruction and deformity
of bones, profound muscle weakness, seizures, respiratory failure and
premature death.1-5
“The NDA submission for asfotase alfa is a critical step toward bringing
this highly innovative and much-needed potential treatment to patients
in Japan suffering from HPP,” said Leonard Bell, M.D., Chairman and
Chief Executive Officer of Alexion. “If approved, asfotase alfa would be
the first therapy for patients with this devastating and
life-threatening disorder.”
The MHLW submission includes positive data from 71 patients with HPP
(ranging from newborns to 66 years of age), including Japanese patients,
enrolled in three pivotal prospective studies and their extensions, as
well as a retrospective natural history study in infants.
In September 2014, the MHLW granted orphan drug designation (ODD) to
asfotase alfa for the treatment of patients with HPP. As a result, the
NDA for asfotase alfa will receive priority review for marketing
authorization, and, if approved, asfotase alfa would have 10 years of
market exclusivity for the designated indication.
About Hypophosphatasia (HPP)
HPP is a genetic, chronic and progressive ultra-rare metabolic disease
characterized by defective bone mineralization that can lead to
destruction and deformity of bones, profound muscle weakness, seizures,
respiratory failure and premature death.1-5
HPP is caused by mutations in the gene encoding 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, and pediatric-onset HPP is 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 Pediatric
patients with HPP have a high mortality rate, with 73% mortality
reported in a natural history study at 5 years.6 In these
patients, mortality is primarily due to respiratory failure.1,5,7 In
patients surviving to adolescence and adulthood, long-term clinical
sequelae include recurrent and non-healing fractures, debilitating
weakness, severe pain and the requirement for ambulatory assistive
devices such as wheelchairs, wheeled walkers and canes.1,4
About Asfotase Alfa
Asfotase alfa is an investigational, highly innovative, first-in-class
targeted enzyme replacement therapy. Asfotase alfa is designed to
address the underlying cause of HPP by aiming to restore the genetically
defective metabolic process, thereby preventing or reversing the severe
and potentially life-threatening complications of life-long dysregulated
mineral metabolism.
In 2013, the U.S. Food and Drug Administration (FDA) granted
Breakthrough Therapy designation for asfotase alfa. According to the
FDA, a Breakthrough Therapy designation is designed to expedite the
development of a drug to treat a serious or life-threatening disease
when preliminary clinical evidence indicates that the drug may
demonstrate substantial improvement over existing therapies on one or
more clinically significant endpoints.
In April 2014, Alexion initiated the rolling submission of a Biologics
License Application (BLA) for asfotase alfa as a treatment for patients
with HPP with the U.S. Food and Drug Administration (FDA). In July 2014,
the Marketing Authorization Application (MAA) for asfotase alfa was
validated and granted accelerated assessment by the European Medicines
Agency (EMA).
About Alexion
Alexion is a biopharmaceutical company focused on serving patients with
severe and rare disorders through the innovation, development and
commercialization of life-transforming therapeutic products. Alexion is
the global leader in complement inhibition and has developed and markets
Soliris® (eculizumab) as a treatment for patients with
paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic
syndrome (aHUS), two debilitating, ultra-rare and life-threatening
disorders caused by chronic uncontrolled complement activation. Soliris
is currently approved in nearly 50 countries for the treatment of PNH
and in nearly 40 countries for the treatment of aHUS. Alexion is
evaluating other potential indications for Soliris in additional severe
and ultra-rare disorders beyond PNH and aHUS, and is developing other
highly innovative biotechnology product candidates, including asfotase
alfa, across multiple therapeutic areas. This press release and further
information about Alexion can be found at: www.alexionpharma.com.
[ALXN-G]
Safe Harbor Statement
This news release contains forward-looking statements, including
statements related to potential medical benefits of asfotase alfa for
hypophosphatasia (HPP). 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
asfotase alfa for HPP, delays in arranging satisfactory manufacturing
capabilities and establishing commercial infrastructure for asfotase
alfa for HPP, the possibility that results of clinical trials are not
predictive of safety and efficacy results of asfotase alfa in broader or
different patient populations, the risk that third party payors
(including governmental agencies) will not reimburse for the use of
asfotase alfa (if approved) at acceptable rates or at all, the risk that
estimates regarding the number of patients with asfotase alfa and
observations regarding the natural history of patients with asfotase
alfa 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 June 30, 2014. 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
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1.
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Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol
Rev. 2013; 10(suppl 2):380-388.
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2.
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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.
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Whyte MP, Greenberg CR, Salman N, et al. Enzyme-replacement
therapy in life-threatening hypophosphatasia. N Engl J Med. 2012;
366(10):904-913.
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Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy with
hypophosphatasia. Arch Dis Child. 1990; 65(1):130-131.
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5.
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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.
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6.
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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.
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7.
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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.
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