Market Overview

Data Presented at WORLDSymposium™ 2018 Show Survival to 3 Years of Age and Improvements in Liver Function in Infants with Lysosomal Acid Lipase Deficiency Treated with Kanuma® (sebelipase alfa)


Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) announced today that the
combined interim data from two ongoing open-label studies, VITAL and
CL-08, show a 3-year survival estimate of 68% in infants with rapidly
progressive lysosomal acid lipase deficiency (LAL-D) treated with
Kanuma® (sebelipase alfa).1 Of the 19 infants who were
enrolled in the studies, 7 infants are surviving and have reached 3
years of age while an additional 6 infants have not yet reached 3 years
of age.1 These infants also benefited from improvements in a
number of key parameters including weight gain and markers of liver
disease and function. There were no discontinuations due to adverse
events. These data were presented at the WORLDSymposium™ in San
Diego and confirm and extend previously published survival data from
these studies.2,3

"Rapidly progressive LAL-D previously meant a death sentence for most
infants diagnosed with this devastating and ultra-rare metabolic
disease," said John Orloff, M.D., Executive Vice President and Global
Head of R&D at Alexion. "It is gratifying and humbling to see that many
of these infants are surviving into childhood when treated with Kanuma®,
while experiencing important improvements in their disease symptoms."

LAL-D is a chronic and progressive ultra-rare metabolic disease, which
can lead to multi-organ damage and premature death.4,5 For
infants with rapidly progressive LAL-D, the median age of death is 3.7
months and mortality by 1 year is nearly 100%.6 LAL-D is
caused by genetic mutations that result in a deficiency in LAL enzyme
activity in the lysosomes, that is vital for the breakdown of lipids.
This deficiency leads to the chronic build-up of lipids (cholesteryl
esters and triglycerides) in the liver, blood vessel walls, the
intestinal system and other organs.4,5 Kanuma® replaces the
lacking or deficient LAL enzyme and is the only approved therapy to
address the underlying cause of LAL-D.7

Effect of Kanuma® on Survival to 3 Years of
Age and Liver Function in Infants with Rapidly Progressive Lysosomal
Acid Lipase Deficiency: Results from 2 Studies

The current analyses evaluated survival and the clinical profile of
infants surviving more than 3 years of age in two ongoing, open-label
studies of Kanuma® in infants who presented with signs or symptoms of
rapidly progressive LAL-D. Patients in the VITAL study (9 patients),
initiated treatment with Kanuma® at a median of 3.0 months of age and
received a starting dose of 0.35 mg/kg once-weekly for the first 2
weeks, with dose escalation up to 1, 3 or 5 mg/kg, per protocol.
Patients in the CL08 study (10 patients) initiated treatment with
Kanuma® at a median of 2.8 months of age and received 1 mg/kg
once-weekly with dose escalation up to 3 or 5 mg/kg, per protocol.

In the VITAL study, 6 of 9 patients survived to 12 months of age and in
CL08 study, 9 of 10 patients survived to 12 months of age. In both
studies, surviving patients had a dose increase to at least 3 mg/kg
once-weekly following protocol-defined criteria.

As of August 2017, the oldest patient had been receiving treatment with
Kanuma® for more than 6 years and is nearly 7 years old (81 months of

For the combined studies, a total of 6 patients died and the causes of
each death were considered by investigators to be unrelated to treatment
with Kanuma®. In the VITAL study, 4 patients died at 2.8, 2.9, 4.3 and
15 months, respectively. In the CL08 study, one patient died at 4.8
months of age and another at 13.8 months of age.

Combined Clinical Trial Results in Detail:

  • Survival: the Kaplan-Meier estimate of survival to 3 years of age was
    68% based on the combined data of both studies.
  • Weight gain: patients' median weight-for-age percentile, as measured
    by percentiles in the World Health Organization (WHO) growth chart of
    the general population, increased from 3.1 at baseline to 25.1 at week
    144 in VITAL; and 0.15 at baseline to 61.7 at week 144 in CL08,
    indicating substantial clinical improvement in growth in both studies.
  • Markers of liver disease and of hematological disease impact:
    • A reduction in the concentration of two liver injury markers,
      alanine aminotransferase (ALT) and aspartate aminotransferase
      (AST), were observed during the course of the treatment period.
      Patients treated with sebelipase alfa for 144 weeks experienced
      changes from Baseline in ALT in the VITAL study (median of 145.0
      U/L at Baseline [n=9] to 32.0 U/L at Week 144 [n=5]), and in the
      CL08 study (median of 37.0 U/L at Baseline [n=9] to 22.5 U/L at
      Week 144 [n=2]). In VITAL, AST decreased from a median of 125.0
      U/L at Baseline (n=9) to 49.5 U/L at Week 144 (n=4). In CL08, AST
      decreased from a median of 99.5 U/L at Baseline (n=8) to 61.0 U/L
      at Week 144 (n=2).
    • Improvements were also observed in liver function, as assessed by
      serum albumin concentration, and in hematologic parameters (i.e.
      hemoglobin concentration) during the course of treatment. Patients
      treated with sebelipase alfa for 144 weeks experienced changes
      from Baseline in serum albumin in the VITAL study (median of 29.0
      g/L at Baseline [n=9] and 34.0 g/L at Week 144 [n=5]) and in the
      CL08 study (median of 20.0 g/L at Baseline [n=9] and 34 g/L at
      Week 144 [n=2]), and a change in hemoglobin in the VITAL study
      (median of 93.0 g/L at Baseline [n=9] and 109.0 g/L at Week 144
      [n=5]), and in the CL08 study (median of 90.0 g/L at Baseline
      [n=7] and 112.0 g/L at Week 144 [n=3]).

All patients experienced one or more treatment emergent adverse events
(TEAEs). Seven patients experienced serious adverse events that were
considered related to sebelipase alfa; all resolved, and there were no
discontinuations due to adverse events.

About Lysosomal Acid Lipase Deficiency (LAL-D)

LAL-D is a genetic, chronic, progressive and potentially
life-threatening, yet underdiagnosed, ultra-rare disease associated with
significant morbidity and premature mortality.5 In patients
with LAL-D, deficient LAL enzyme activity leads to marked accumulation
of lipids (cholesteryl esters and triglycerides) in vital organs, blood
vessels, and other tissues, resulting in rapid and progressive
multi-organ damage including liver fibrosis and cirrhosis, liver
failure, accelerated atherosclerosis, cardiovascular disease, and, in
some cases, death or other devastating consequences.4,5

LAL-D affects patients of all ages and symptoms may manifest at any time
from infancy through adulthood. For LAL-D patients with symptoms
presenting in infancy, the median age of death is 3.7 months and
mortality by 12 months is nearly 100%.6 For those who develop
symptoms as children or adults, approximately 50% progress to liver
fibrosis, cirrhosis, or transplant within 3 years.8 Lack of
disease awareness of LAL-D has contributed to inadequate testing rates
despite the ability to diagnose LAL-D with a simple blood test.9,10

About Kanuma® (sebelipase alfa)

Kanuma® (sebelipase alfa) is an innovative enzyme replacement therapy
that addresses the underlying cause of lysosomal acid lipase deficiency
(LAL-D) by replacing the missing vital enzyme and reducing lipid
substrate accumulation in the lysosomes of cells throughout the body. In
clinical studies, treatment with Kanuma® improved survival in infants
with LAL-D and led to normal development. Kanuma treatment in children
and adults in clinical studies led to rapid and significant reductions
in alanine aminotransferase (ALT) and liver fat content, as well as
significant improvements in lipid parameters, which were sustained with
long-term treatment. Patients treated with Kanuma® have also shown
improvements in liver damage (as measured by Ishak fibrosis stage

Kanuma® is approved in the United States, European Union, Japan, and
other countries around the world. For its innovation in treating
patients with LAL-D, Kanuma® received the prestigious 2016 German Prix
Galien Award in the Orphan Product category.



Hypersensitivity reactions, including anaphylaxis, have been reported in
KANUMA-treated patients. In clinical trials, 3 of 106 (3 percent)
patients treated with KANUMA experienced signs and symptoms consistent
with anaphylaxis. These patients experienced reactions during infusion
with signs and symptoms including chest discomfort, conjunctival
injection, dyspnea, generalized and itchy rash, hyperemia, swelling of
eyelids, rhinorrhea, severe respiratory distress, tachycardia,
tachypnea, and urticaria. Anaphylaxis has occurred as early as the sixth
infusion and as late as 1 year after treatment initiation.

In clinical trials, 21 of 106 (20 percent) KANUMA-treated patients,
including 9 of 14 (64 percent) infants and 12 of 92 (13 percent)
pediatric patients, 4 years and older, and adults experienced signs and
symptoms either consistent with or that may be related to a
hypersensitivity reaction. Signs and symptoms of hypersensitivity
reactions, occurring in two or more patients, included abdominal pain,
agitation, fever, chills, diarrhea, eczema, edema, hypertension,
irritability, laryngeal edema, nausea, pallor, pruritus, rash, and
vomiting. The majority of reactions occurred during or within 4 hours of
the completion of the infusion. Patients were not routinely
pre-medicated prior to infusion of KANUMA in these clinical trials.

Due to the potential for anaphylaxis, appropriate medical support should
be readily available when KANUMA is administered.

Consider the risks and benefits of re-administering KANUMA following a
severe reaction. Monitor patients, with appropriate resuscitation
measures available, if the decision is made to re-administer the product.

Hypersensitivity to Eggs or Egg Products

Patients with a known history of egg allergies were excluded from the
clinical trials. Consider the risks and benefits of treatment with
KANUMA in patients with known systemic hypersensitivity reactions to
eggs or egg products.


The most common adverse reactions are:

In Patients with Rapidly Progressive Disease Presenting within the First
6 Months of Life (≥30 percent): diarrhea, vomiting, fever, rhinitis,
anemia, cough, nasopharyngitis, and urticaria.

In Pediatric and Adult Patients (≥8 percent): headache, fever,
oropharyngeal pain, nasopharyngitis, asthenia, constipation, and nausea.

Please click here
for the full Prescribing Information.

About Alexion

Alexion Pharmaceuticals, Inc. is a global biopharmaceutical company
focused on bringing hope to patients and families affected by rare
diseases by delivering innovative, life-changing therapies. Alexion
developed and commercializes the first and only approved complement
inhibitor to treat patients with paroxysmal nocturnal hemoglobinuria
(PNH), atypical hemolytic uremic syndrome (aHUS), and anti-acetylcholine
receptor (AChR) antibody-positive generalized myasthenia gravis (gMG).
In addition, Alexion 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). As the leader in complement biology for over 20 years, 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.
This press release and further information about Alexion can be found



1.   Jones S, Vijay S, et al. Effect of Sebelipase Alfa on Survival to 3
Years of Age and Liver Function in Infants with Rapidly Progressive
Lysosomal Acid Lipase Deficiency: Results from 2 Studies. Poster
presented at the WorldSymposium™ Annual Meeting 2018, San Diego, CA,
February 6. Poster 173.
2. Jones SA, et al. Survival in infants treated with sebelipase Alfa
for lysosomal acid lipase deficiency: an open-label, multicenter,
dose-escalation study. Orphanet J Rare Dis. 2017 Feb 8;12(1):25.
doi: 10.1186/s13023-017-0587-3.

Jones S, Vijay S, et al. Survival of infants with rapidly
progressive lysosomal acid lipase deficiency treated with
sebelipase alfa. Poster presented at the North American Society
for Pediatric Gastroenterology, Hepatology and Nutrition
(NASPGHAN) Annual Meeting, Las Vegas, NV, November 2, 2017.


4. Reiner Z, et al. Lysosomal acid lipase deficiency – an
under-recognized cause of dyslipidemia and liver dysfunction.
Atherosclerosis. 2014;235:21-30.
5. Bernstein DL, et al. Cholesteryl ester storage disease: review of
the findings in 135 reported patients with an underdiagnosed
disease. J Hepatol. 2013;58:1230-43.
6. Jones SA, et al. Rapid progression and mortality of lysosomal acid
lipase deficiency presenting in infants. Genetics in Medicine. 2016
7. Kanuma® (sebelipase alfa) Full Prescribing Information.
8. Burton et al. Progression of liver disease in children and adults
with lysosomal acid lipase deficiency. Current Medical Research and
Opinion. 2017; Vol. 33,Iss. 7.
9. Burton BK et al. Clinical Features of Lysosomal Acid Lipase
Deficiency. J Pediatr Gastroenterol Nutr. 2015;61:619-25.
10. 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.
11. Goodman ZD, et al. Change in liver fibrosis in children and adults
with lysosomal acid lipase deficiency after 52 weeks of sebelipase
alfa (ARISE trial) [AASLD abstract 561]. Hepatology.
2016;64:136-361. doi:10.1002/hep.28797/full.

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