- Patients experienced sustained improvements
in physical function, speed, agility, and strength -
Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) announced today
that researchers presented data showing that the rapid benefits of
Strensiq® (asfotase alfa) achieved in adolescents and adults (ages
13-66 years at study entry) with hypophosphatasia (HPP) within the
first 6 months were sustained through 5 years of treatment.1 These
are the final data from the extension phase of a randomized,
open-label, dose-ranging Phase 2 trial of Strensiq and they confirm
previously presented interim results.
The results were presented at the European Calcified Tissue
Society (ECTS) Congress in Austria and demonstrate a reduction in
two key biomarkers of HPP disease activity, as well as improvements
in physical function in patients treated with Strensiq, as observed
in tests to measure walking distance, running speed and agility,
and muscle strength. Strensiq was generally well-tolerated. The
most common treatment-related adverse events were mild to moderate
injection-site reactions.1
“The findings of this phase 2 study suggest that asfotase alfa
appears to be safe and effective long-term and reduces the
debilitating burden of HPP in adolescent and adult patients,” said
lead author, Priya S. Kishnani, M.D., Division Chief, Medical
Genetics, Duke University School of Medicine, Durham, North
Carolina. “Patients with HPP can suffer multiple fractures,
deformities, short stature, impaired mobility, pain, and limited
activities of daily living.”
Strensiq is approved in the United States as a treatment for
patients with perinatal-, infantile- or juvenile-onset HPP.
Strensiq is also approved in Australia, Canada, the European Union,
Israel, Japan, South Korea, and Switzerland.
Further details of the study results1
- Reductions in plasma concentrations of
plasma pyridoxal 5’ phosphate (PLP) and inorganic pyrophosphate
(PPi) levels at 6 months were greater in patients treated with
Strensiq than in the control group. PLP and PPi are substrates of
the enzyme (tissue non-specific alkaline phosphatase, TNSALP) that
patients with HPP lack and that Strensiq replaces. As such, PLP and
PPi are biomarkers to measure reduction in HPP disease activity.
Decreases from Baseline in both PLP and PPi levels were maintained
through 5 years.
- Physical function, as measured by the
Six Minute Walk Test (6MWT), improved from a median of 76 percent
of that predicted for healthy peers at Baseline (n=15; below normal
range) to a median of 85 percent predicted (n=16; within the normal
range) by 6 months in patients treated with Strensiq. Results were
sustained through 5 years of treatment and increased to 88 percent
(n=11) at 5 years.
- Speed and agility, as measured by
median change from Baseline in the BOT-2 Running Speed and Agility
subscale, increased by a median of 4 points after 5 years of
treatment (n=11).
- Strength, as measured by median change
from Baseline in the BOT-2 Strength subscale, increased by a median
of 3.5 points after 5 years of treatment (n=12).
- 1 patient withdrew because of serious
AEs of injection site hypersensitivity and anaphylactoid reaction
(1 episode each). This patient subsequently received Strensiq
post-marketing without reaction. All patients experienced ≥1
treatment-emergent adverse event (TEAE); the majority of TEAEs were
mild in intensity.
In the primary phase of this study, patients were randomized to
receive no treatment (n=6), 0.3 mg/kg/day of Strensiq (n=7), or 0.5
mg/kg/day of Strensiq (n=6) for 6 months. The majority of patients
(with the exception of 1 adult patient) had confirmed
pediatric-onset HPP. At 6 months, all 19 patients entered the
extension phase of the study and were treated with 0.5 mg/kg/day of
Strensiq, then changed to 1 mg/kg/day, 6 times a week, over the
next 6 to 12 months. Fourteen patients completed the study over 5
years. Data from both Strensiq dosage groups were pooled for the
primary analysis.
The approved dosing regimen for patients with
perinatal/infantile-onset and juvenile-onset HPP is 2 mg/kg
administered subcutaneously three times per week, or 1 mg/kg
administered six times per week. (The U.S. Prescribing Information
recommends increasing the dose to 3 mg/kg three times per week in
patients with infantile-onset HPP in cases of insufficient
efficacy).
About Hypophosphatasia (HPP)
HPP is a genetic, chronic, progressive, and potentially
life-threatening ultra-rare metabolic disease that can affect
people of all ages. HPP is characterized by defective bone
mineralization that can lead to weakness and deformity of bones,
fractures and other skeletal abnormalities, as well as systemic
complications such as profound muscle weakness, muscle, bone and
joint pain, seizures in perinatal/infantile forms of HPP, and
respiratory failure leading to premature death in infants.2-6 HPP
is traditionally classified by the age of the patient at the onset
of symptoms of the disease, with perinatal-, infantile- and
juvenile-onset HPP defined by the onset of the first symptom prior
to 18 years of age.
HPP can have devastating consequences for patients at any stage
of life.2 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 percent at 5
years.7 In these patients, mortality was primarily due to
respiratory failure.2,6,8 In patients surviving and those with
juvenile-onset HPP, long-term clinical sequelae include recurrent
and non-healing fractures, profound muscle weakness, debilitating
pain, and the requirement for ambulatory assistive devices such as
wheelchairs, wheeled walkers and canes.2,5
HPP is caused by mutations in the gene encoding an enzyme known
as tissue non-specific alkaline phosphatase (TNSALP). This enzyme
plays a critical role in the proper mineralization of bones.2,3
About Strensiq® (asfotase alfa)
Strensiq® (asfotase alfa) is a highly innovative bone-targeted
enzyme replacement therapy that treats the underlying cause of HPP
by replacing the missing TNSALP enzyme. In clinical studies of
patients with HPP who had their first symptom prior to the age of
18, treatment with Strensiq improved overall survival in infants,
enhanced bone mineralization and improved height, weight and
mobility.
Strensiq is approved in Australia, Canada, the European Union,
Israel, Japan, South Korea, and Switzerland, and the United
States.
IMPORTANT SAFETY INFORMATION
Hypersensitivity reactions, including anaphylaxis, have been
reported in STRENSIQ-treated patients. Signs and symptoms
consistent with anaphylaxis included difficulty breathing, choking
sensation, nausea, periorbital edema, and dizziness. These
reactions have occurred within minutes after subcutaneous
administration of STRENSIQ and can occur in patients on treatment
for more than one year. Other hypersensitivity reactions have also
been reported in STRENSIQ-treated patients, including vomiting,
fever, headache, flushing, irritability, chills, skin erythema,
rash, pruritus and oral hypoesthesia. If a severe hypersensitivity
reaction occurs, discontinue STRENSIQ treatment and initiate
appropriate medical treatment. Consider the risks and benefits of
re-administering STRENSIQ to individual patients following a severe
reaction. If the decision is made to re-administer the product,
monitor patients for a reoccurrence of signs and symptoms of a
severe hypersensitivity reaction.
Localized lipodystrophy, including lipoatrophy and
lipohypertrophy, has been reported at injection sites after several
months in patients treated with STRENSIQ. Advise patients to follow
proper injection technique and to rotate injection sites.
Patients with HPP are at increased risk for developing ectopic
calcifications. In clinical trials, 14 cases (14%) of ectopic
calcification of the eye, including the cornea and conjunctiva, and
the kidneys (nephrocalcinosis) were reported. There was
insufficient information to determine whether or not the reported
events were consistent with the disease or due to STRENSIQ. No
visual changes or changes in renal function were reported.
Ophthalmology examinations and renal ultrasounds are recommended at
baseline and periodically during treatment with STRENSIQ to monitor
for signs and symptoms of ophthalmic and renal ectopic
calcifications and for changes in vision or renal function.
The most common adverse reactions (≥ 10%) are injection site
reactions, lipodystrophy, ectopic calcifications and
hypersensitivity reactions.
Please click here for the full Prescribing Information.9
About Alexion
Alexion is a global biopharmaceutical company focused on
developing and delivering life-transforming therapies for patients
with devastating and rare disorders. Alexion is the global leader
in complement inhibition and has developed and commercializes 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.
In addition, Alexion’s metabolic franchise includes two highly
innovative enzyme replacement therapies for patients with
life-threatening and ultra-rare disorders, hypophosphatasia (HPP)
and lysosomal acid lipase deficiency (LAL-D). Alexion is advancing
its rare disease pipeline with highly innovative product candidates
in multiple therapeutic areas. 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). Forward-looking
statements are subject to factors that may cause Alexion’s results
and plans to differ from those expected, including, for example,
risks and uncertainties of drug development, decisions of
regulatory authorities regarding the adequacy of our research,
marketing approval or material limitations on the marketing of
Strensiq for HPP, delays in arranging satisfactory manufacturing
capabilities and establishing commercial infrastructure for
Strensiq for HPP, the possibility that results of clinical trials
are not predictive of safety and efficacy results of Strensiq in
broader or different patient populations, the adequacy of our
pharmacovigilance and drug safety reporting processes, the risk
that estimates regarding the number of patients with Strensiq and
observations regarding the natural history of patients with
Strensiq 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, 2017 and in Alexion's other filings with the SEC.
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. Kishnani P, Rockman-Greenberg, C, Denker A, et al.
Biochemical and Physical Function Outcomes in Adolescents and
Adults With Hypophosphatasia Treated With Asfotase Alfa for 5
Years: Results From a Phase 2 Study. Poster presented at the
European Calcified Tissue Society Congress, Salzburg, Austria, May
15, 2016.
2. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol
Rev. 2013; 10(suppl 2):380-388.
3. 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.
4. Whyte MP, Greenberg CR, Salman N, et al. Enzyme-replacement
therapy in life-threatening hypophosphatasia. N Engl J Med. 2012;
366(10):904-913.
5. Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy
with hypophosphatasia. Arch Dis Child. 1990; 65(1):130-131.
6. 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.
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. U.S. Prescribing Information for STRENSIQ® (asfotase
alfa)
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Alexion Pharmaceuticals, Inc.MediaEmily Vlasak,
475-230-3782Associate Director, Corporate
CommunicationsORInvestorsElena Ridloff, CFA, 475-230-36014Vice
President, Investor Relations
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