STAINES-UPON-THAMES, United
Kingdom, March 5, 2020
/PRNewswire/ -- Mallinckrodt plc
(NYSE: MNK), a global biopharmaceutical company, today announced
publication of findings from a prospective, open-label pilot study
to assess the efficacy and safety of Acthar® Gel
(repository corticotropin injection) in patients with
immunoglobulin A nephropathy (IgAN) at high risk of chronic kidney
disease progression.1 The study was published in
Kidney International Reports, the journal of the
International Society of Nephrology. IgAN, also known as Berger's
disease, is a kidney disease that occurs when IgA deposits build up
in the kidneys, causing inflammation that damages kidney
tissues2,3
The study, titled "An Open-Label Pilot Study of
Adrenocorticotrophic Hormone in the Treatment of lgA Nephropathy at
High Risk of Progression," demonstrated that treatment with Acthar
Gel resulted in a significant reduction in 24-hour urinary protein
(P=0.007) with a stable estimated glomerular filtration rate (eGFR)
(P=0.1) – a measure of renal function – following six months of
treatment with 80 units twice weekly, and an additional six-month
follow up. Elevated amounts of urinary protein (>1 g/24 hours)
are associated with increased risk of progression to end-stage
renal disease and up to 50 percent of patients with IgAN and
proteinuria will progress to end-stage renal disease within 15
years.1 No patients discontinued the study due to side
effects and there were no serious adverse events reported. Six
patients were treated for infections. The most common other adverse
events were injection reaction, muscle soreness, acne, hot flashes,
anxiety and insomnia.1
Acthar® Gel (repository corticotropin injection)
is indicated to induce a diuresis or a remission of proteinuria
(excess protein in the urine) in nephrotic syndrome without uremia
of the idiopathic type or that due to lupus
erythematosus.4 Please see Important Safety Information
for Acthar Gel below.
"IgAN is a clinically challenging immune-mediated kidney disease
in which patients are at risk of rapidly progressing to end-stage
renal disease, yet there are limited therapeutic options for the
reduction of proteinuria in IgAN available to physicians and
patients," said Tunde Otulana,
M.D., Senior Vice President and Chief Medical Officer at
Mallinckrodt. "We are encouraged by
these results and are committed to supporting additional research
in this patient population with unmet needs."
Study Methods1
- The prospective, open-label study assessed 19 patients >18
years of age with biopsy-proven IgAN treated with Acthar Gel 80
units subcutaneously twice weekly for six months and followed
patients for a total of 12 months.
- Subjects were required to have a urinary protein >1 g/24
hours despite adequate renin-angiotensin system inhibition and eGFR
>30 ml/min at enrollment.
- The primary endpoint was: change in proteinuria and eGFR from
baseline to 12 months. Complete response was defined as a 24-hour
urinary protein <300 mg and ≤10 percent reduction in eGFR and
partial response was defined as a >50 percent reduction in
urinary protein and ≤25 percent reduction in eGFR.
- The primary safety endpoint was incidence of infections
(pneumonia, urinary tract infections and pyelonephritis) and rate
of developing diabetes.
Key Findings1
- The study demonstrated a significant reduction in 24-hour
urinary protein from mean 2.6 to 1.3 g (P=0.007) at 12-month
follow-up after being treated with Acthar Gel.
- Following treatment with Acthar Gel, patients had stable eGFR,
a measure for kidney function (mean 65.5 to 61.1 ml/min,
P=0.1).
- Eight patients (42 percent) achieved partial remission (PR).
There were no complete remissions. Of the eight patients who
achieved PR, seven had proteinuria less than 1 g at 12 months, with
a median 24-hour urinary protein of 625 mg (344–1458 mg).
- Fifty-three adverse events (AEs) were reported, including six
infections (two viral and four bacterial) that were treated
effectively with anti-infectives. No serious AEs were reported and
no patients developed hyperglycemia.
Study Limitations1
- Results may not be solely attributable to Acthar Gel.
- This study's small sample size and lack of a placebo group for
comparison limit the ability to make associations between clinical
outcomes and potential predictors.
- Due to the limited follow-up, it is not known what long-term
outcomes patients experienced, including changes in eGFR, which may
occur over a longer period of time.
"Patients with IgAN are at risk of renal failure progressing to
end-stage renal disease," said James A.
Tumlin, M.D., FASN, Professor of Medicine at Emory University. "There is a great need to
identify effective treatment options for these patients, and it's
encouraging to see new research in this area of high unmet
need."
About IgA Nephropathy
Immunoglobulin A (IgA)
nephropathy is one of the most common kidney
diseases.2,5 Also known as Berger's disease, IgAN
is a kidney disease that occurs when the IgA deposits build up in
the kidneys.2 IgA is an antibody produced by the body's
immune system.3 Buildup of IgA antibodies results
in inflammation that may hamper the kidneys' ability to filter
wastes from the blood over time.5 While IgA
nephropathy often progresses slowly over many years, the course of
the disease can vary in each patient. Some patients may experience
blood in their urine without developing problems, some may achieve
complete remission, while others develop end-stage kidney
failure.3,5 While there is no cure for IgAN,
certain medications can slow its course.3,5 IgAN
can occur at any age, although the first evidence of kidney disease
most frequently appears when people are in their teens to late
30s.3 In the U.S., IgAN is twice as likely to appear in
men than in women.3 While found in people all over
the world, IgAN is more common among Asians and
Caucasians.6
Acthar® Gel (repository corticotropin
injection) is indicated for:
- Treatment during an exacerbation or as maintenance therapy in
selected cases of systemic lupus erythematosus
- Monotherapy for the treatment of infantile spasms in infants
and children under 2 years of age
- The treatment of acute exacerbations of multiple sclerosis in
adults. Controlled clinical trials have shown Acthar Gel to be
effective in speeding the resolution of acute exacerbations of
multiple sclerosis. However, there is no evidence that it affects
the ultimate outcome or natural history of the disease
- Inducing a diuresis or a remission of proteinuria in nephrotic
syndrome without uremia of the idiopathic type or that due to lupus
erythematosus
- Treatment during an exacerbation or as maintenance therapy in
selected cases of systemic dermatomyositis (polymyositis)
- The treatment of symptomatic sarcoidosis
- Adjunctive therapy for short-term administration (to tide the
patient over an acute episode or exacerbation) in: psoriatic
arthritis, rheumatoid arthritis, including juvenile rheumatoid
arthritis (selected cases may require low-dose maintenance
therapy), ankylosing spondylitis
- Treatment of severe acute and chronic allergic and inflammatory
processes involving the eye and its adnexa such as: keratitis,
iritis, iridocyclitis, diffuse posterior uveitis and choroiditis,
optic neuritis, chorioretinitis, anterior segment inflammation
IMPORTANT SAFETY INFORMATION
Contraindications
- Acthar should never be administered intravenously
- Administration of live or live attenuated vaccines is
contraindicated in patients receiving immunosuppressive doses of
Acthar
- Acthar is contraindicated where congenital infections are
suspected in infants
- Acthar is contraindicated in patients with scleroderma,
osteoporosis, systemic fungal infections, ocular herpes simplex,
recent surgery, history of or the presence of a peptic ulcer,
congestive heart failure, uncontrolled hypertension, primary
adrenocortical insufficiency, adrenocortical hyperfunction or
sensitivity to proteins of porcine origins
Warnings and Precautions
- The adverse effects of Acthar are related primarily to its
steroidogenic effects
- Acthar may increase susceptibility to new infection or
reactivation of latent infections
- Suppression of the hypothalamic-pituitary-axis (HPA) may occur
following prolonged therapy with the potential for adrenal
insufficiency after withdrawal of the medication. Adrenal
insufficiency may be minimized by tapering of the dose when
discontinuing treatment. During recovery of the adrenal gland
patients should be protected from the stress (e.g. trauma or
surgery) by the use of corticosteroids. Monitor patients for
effects of HPA suppression after stopping treatment
- Cushing's syndrome may occur during therapy but generally
resolves after therapy is stopped. Monitor patients for signs and
symptoms
- Acthar can cause elevation of blood pressure, salt and water
retention, and hypokalemia. Blood pressure, sodium and potassium
levels may need to be monitored
- Acthar often acts by masking symptoms of other
diseases/disorders. Monitor patients carefully during and for a
period following discontinuation of therapy
- Acthar can cause GI bleeding and gastric ulcer. There is also
an increased risk for perforation in patients with certain
gastrointestinal disorders. Monitor for signs of bleeding
- Acthar may be associated with central nervous system effects
ranging from euphoria, insomnia, irritability, mood swings,
personality changes, and severe depression, and psychosis. Existing
conditions may be aggravated
- Patients with comorbid disease may have that disease worsened.
Caution should be used when prescribing Acthar in patients with
diabetes and myasthenia gravis
- Prolonged use of Acthar may produce cataracts, glaucoma and
secondary ocular infections. Monitor for signs and symptoms
- Acthar is immunogenic and prolonged administration of Acthar
may increase the risk of hypersensitivity reactions. Neutralizing
antibodies with chronic administration may lead to loss of
endogenous ACTH activity
- There is an enhanced effect in patients with hypothyroidism and
in those with cirrhosis of the liver
- Long-term use may have negative effects on growth and physical
development in children. Monitor pediatric patients
- Decrease in bone density may occur. Bone density should be
monitored for patients on long-term therapy
- Pregnancy Class C: Acthar has been shown to have an embryocidal
effect and should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus
Adverse Reactions
- Common adverse reactions for Acthar are similar to those of
corticosteroids and include fluid retention, alteration in glucose
tolerance, elevation in blood pressure, behavioral and mood
changes, increased appetite and weight gain
- Specific adverse reactions reported in IS clinical trials in
infants and children under 2 years of age included: infection,
hypertension, irritability, Cushingoid symptoms, constipation,
diarrhea, vomiting, pyrexia, weight gain, increased appetite,
decreased appetite, nasal congestion, acne, rash, and cardiac
hypertrophy. Convulsions were also reported, but these may actually
be occurring because some IS patients progress to other forms of
seizures and IS sometimes mask other seizures, which become visible
once the clinical spasms from IS resolve
Other adverse events reported are included in the full
Prescribing Information.
Please see full Prescribing Information for
additional Important Safety Information.
ABOUT MALLINCKRODT
Mallinckrodt is a global business consisting of
multiple wholly owned subsidiaries that develop, manufacture,
market and distribute specialty pharmaceutical products and
therapies. The company's Specialty Brands reportable segment's
areas of focus include autoimmune and rare diseases in specialty
areas like neurology, rheumatology, nephrology, pulmonology and
ophthalmology; immunotherapy and neonatal respiratory critical care
therapies; analgesics and gastrointestinal products. Its Specialty
Generics reportable segment includes specialty generic drugs and
active pharmaceutical ingredients. To learn more about Mallinckrodt, visit www.mallinckrodt.com.
Mallinckrodt uses its website as a
channel of distribution of important company information, such as
press releases, investor presentations and other financial
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Securities and Exchange Commission (SEC) disclosing the same
information. Therefore, investors should look to the Investor
Relations page of the website for important and time-critical
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information is made available on the Investor Relations page of the
website.
CAUTIONARY STATEMENTS RELATED TO FORWARD-LOOKING
STATEMENTS
This release includes forward-looking statements
concerning Acthar Gel including its potential impact on patients
and anticipated benefits associated with its use. The statements
are based on assumptions about many important factors, including
the following, which could cause actual results to differ
materially from those in the forward-looking statements:
satisfaction of regulatory and other requirements; actions of
regulatory bodies and other governmental authorities; changes in
laws and regulations; issues with product quality, manufacturing or
supply, or patient safety issues; and other risks identified and
described in more detail in the "Risk Factors" section of
Mallinckrodt's most recent Annual
Report on Form 10-K and other filings with the SEC, all of which
are available on its website. The forward-looking statements made
herein speak only as of the date hereof and Mallinckrodt does not assume any obligation to
update or revise any forward-looking statement, whether as a result
of new information, future events and developments or otherwise,
except as required by law.
CONTACTS
For Trade Media
Inquiries
Caren Begun
Green Room Communications
201-396-8551
caren@greenroompr.com
For Financial/Dailies Media Inquiries
Jim Heins
H+K Strategies
212-885-0463
jim.heins@hkstrategies.com
Investor Relations
Daniel J.
Speciale, CPA
Vice President, Investor Relations and IRO
314-654-3638
daniel.speciale@mnk.com
Mallinckrodt, the "M" brand mark and
the Mallinckrodt Pharmaceuticals logo are trademarks of
a Mallinckrodt company. Other brands are trademarks of
a Mallinckrodt company or their respective
owners. ©2020 Mallinckrodt. US-2000135 3/20
References
1 Zand, L, Canetta P, Lafayette R, Aslam N, Jan
N, Sethi S, et al. An Open-Label Pilot Study of
Adrenocorticotrophic Hormone in the Treatment of IgA Nephropathy at
High Risk of Progression. Kidney Int Rep, Volume 5, Issue 1, 58-65.
doi: 10.1016/j.ekir.2019.10.007. eCollection 2020 Jan.
2 Schena FP, Nistor I. Epidemiology of IgA
Nephropathy: A global perspective. Semin. Nephrol. 2018;38(5):
435–442. doi: 10.1016/j.semnephrol.2018.05.013.
3 Wyatt RJ, Julian BA. IgA Nephropathy. N Engl J
Med. 2013;368(25):2402–2414. DOI: 10.1056/NEJMra1206793
4 Acthar® Gel (repository
corticotropin injection) [prescribing
information]. Mallinckrodt ARD LLC.
5 Lafayette RA, Kelepouris E. Immunoglobulin A
nephropathy: advances in understanding of pathogenesis and
treatment. Am J Nephrol 2018;47(suppl 1):43–52. doi:
10.1159/000481636.
6 Satpathy HK. IgA Nephropathy. In: Ferri FF, ed.
Ferri's Clinical Advisor 2013. 1st ed. St. Louis: Mosby; 2012: 570–571.
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