STAINES-UPON-THAMES, United
Kingdom, Nov. 26, 2019
/PRNewswire/ -- Mallinckrodt plc (NYSE:
MNK), a global biopharmaceutical company, today announced findings
from a large retrospective study of Acthar® Gel
(repository corticotropin injection) in the treatment of the
respiratory disease symptomatic sarcoidosis that assessed patient
characteristics, treatment patterns, concomitant medication use and
physicians' assessments of treatment response. The study examined
medical records from 302 patients with advanced symptomatic
sarcoidosis, the majority of whom had comorbidities and had
previously been treated with corticosteroids. The analysis showed
that the use of Acthar Gel was associated with improved overall
health status in 95 percent of patients as reported by physicians'
assessments, with more than half of patients (54 percent) seeing
improvements in two or more symptoms. In addition, there was an
association observed between the use of Acthar Gel therapy and
reduced overall use of other medications. Results of the study were
recently published online in Therapeutic Advances in Respiratory
Disease, an online, open-access peer-reviewed journal.
Acthar Gel is approved by the U.S. Food and Drug
Administration (FDA) for the treatment of symptomatic
sarcoidosis.1 Please see Important Safety Information
for Acthar Gel below.
"Symptomatic sarcoidosis is a rare and clinically challenging
multisystem disease2,3 with high-dose corticosteroids as
the mainstay of therapy. Mallinckrodt
is committed to better understanding patients who may need an
alternative to corticosteroids," said George Wan, Ph.D., Vice President and Global
Head of Health Economics and Outcomes Research at Mallinckrodt. "This study examined records from
a large group of patients with advanced symptomatic sarcoidosis,
and as such provides real-world data to support the use of Acthar
Gel therapy in clinical practice in appropriate patients."
The study, titled "Repository corticotropin injection in
patients with advanced symptomatic sarcoidosis: retrospective
analysis of medical records," evaluated patient records from 302
adult (≥18, mean age=51 years) patients who were treated with
Acthar Gel in the previous 36 months at the time of data collection
from September 2017 to November 2017.
Study Methods
Patients were required to have completed an individualized
course of Acthar Gel therapy or received Acthar Gel for ≥6 months
at the time of data collection. Records were analyzed from 98
physicians in a range of specialties, including pulmonology,
rheumatology, primary care, dermatology, cardiology, ophthalmology,
gastroenterology and neurology.
- Sixty-four percent of patients had chest imaging and
biopsy-confirmed stage 3 or 4 sarcoidosis and 30 percent had been
hospitalized for sarcoidosis during the previous year.
- All patients had evidence of pulmonary involvement; 42 percent
had involvement of one extrapulmonary organ and 34 percent had
involvement in multiple extrapulmonary organs, most commonly the
skin (28 percent), joints (25 percent), heart (22 percent) and eyes
(22 percent).
- Patients' symptoms included mild-to-moderate shortness of
breath, fatigue, bone and joint pain, wheezing/coughing and
abnormal heartbeat prior to treatment with Acthar Gel.
- 76% of patients reported 1 or more comorbidities; 24 percent
had no comorbid conditions.
- The study examined concurrent medication use before, during and
after Acthar Gel therapy. Eighty-six percent of patients had
received other treatments in the three months prior to receiving
Acthar Gel and concurrent medications used included oral
corticosteroids, biologics, immunosuppressants and antimalarial
agents.
Additional Observations
The analysis found that patients had varied and individualized
dosing regimens. The mean duration of Acthar Gel treatment was 32.5
weeks, with 61.6 percent of patients continuing treatment for ≥6
months.
- Use of Acthar Gel was associated with a reduction in the use of
other medications.
- Acthar Gel was also associated with an overall decrease in use
of corticosteroids from 61.3 percent during the three months before
Acthar Gel initiation to 12.9 percent three months after the start
of Acthar Gel therapy.
- The analysis also showed an association between Acthar Gel
treatment and a decrease in the mean daily dose of corticosteroids
from 18.2 mg to 9.9 mg.
According to physicians' assessments of change in patient health
status following Acthar Gel therapy, improvements were reported in:
overall health status (95 percent) as measured by the question
"What is the patient's status as of the end of RCI therapy or the
six months point in therapy for ongoing treatment patients?" In
addition, physicians reported overall reduced symptoms (73
percent); improved lung function (38 percent); reduced inflammation
(33 percent); reduction or discontinuation of corticosteroids (32
percent); and increased quality of life (32 percent).
Limitations
- The study's retrospective design is limited by data collected
from patient medical records that could have errors or omissions.
Outcomes may be influenced by therapies not documented in the
chart.
- Most patients were on multiple therapies; the clinical outcomes
may not be solely attributable to Acthar Gel.
- There is an inherent risk of bias resulting in overestimation
of the effectiveness of Acthar Gel based on a subjective endpoint
such as physicians' assessments.
- As with any retrospective design, data are exploratory and
hypothesis-generating and comparisons between Acthar Gel and
control groups or other treatments cannot be made.
- The study did not capture adverse reactions in this cohort of
patients with symptomatic sarcoidosis.
The analysis was conducted by Mallinckrodt. The company is also currently
conducting a Phase 4, multicenter, randomized, double-blind,
placebo-controlled pilot study evaluating the efficacy and safety
of Acthar Gel in the treatment of pulmonary sarcoidosis. Read
more at: https://clinicaltrials.gov/ct2/show/NCT03320070.
About Sarcoidosis
Sarcoidosis is a challenging, yet
manageable, rare multisystem disease.2,3 In some cases
the symptoms may come and go throughout a lifetime. This is
referred to as symptomatic sarcoidosis. In people with sarcoidosis,
the immune system overreacts, forming clumps of cells called
granulomas that result in inflammation to the body's
tissues.4 The disease can impact any organ, but it most
often impacts the lungs, lymph nodes, eyes, and skin.2
Over 90 percent of people with sarcoidosis suffer lung
problems.4 Concomitant involvement of organs outside of
the lungs is common, occurring in as many as half of all
sarcoidosis cases.5
Acthar Gel (repository corticotropin
injection) Indications
Acthar Gel is an injectable
drug approved by the FDA for the treatment of 19
indications. Of these, today the majority of Acthar use is in these
indications:
- Adjunctive therapy for short-term administration (to tide the
patient over an acute episode or exacerbation) in rheumatoid
arthritis, including juvenile rheumatoid arthritis (selected cases
may require low-dose maintenance therapy)
- The treatment of symptomatic sarcoidosis
- Monotherapy for the treatment of infantile spasms in infants
and children under 2 years of age
- Treatment during an exacerbation or as maintenance therapy in
selected cases of systemic lupus erythematosus
- 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)
- 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.
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 information. It also uses its
website to expedite public access to time-critical information
regarding the company in advance of or in lieu of distributing a
press release or a filing with the U.S. 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 information. Visitors
to the website can also register to receive automatic e-mail and
other notifications alerting them when new 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 expectations regarding related
clinical trials, 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
Daniel Yunger
Kekst CNC
212-521-4879
mallinckrodt@kekstcnc.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. ©2019 Mallinckrodt. US-1901951 11/19
References
1 Acthar® Gel (repository
corticotropin injection) [prescribing
information]. Mallinckrodt ARD, Inc.
2 Judson MA. The clinical features of sarcoidosis:
a comprehensive review. Clin Rev Allerg Immunol. 2015;49:63-78.
3 Boughman 2016 Baughman RP, Field S, Costabel U,
et al. Sarcoidosis in America. Analysis based on health care use.
Ann Am Thorac Soc 2016;13:1244-1252.
4 Baughman RP, Culver DA, Judson MA. A concise
review of pulmonary sarcoidosis. Am J Respir Crit Care Med.
2011;183:573-581.
5 Shigemitsu H, Patel HV, Schreiber MP.
Extrapulmonary sarcoidosis. In: Judson MA, ed. Pulmonary
Sarcoidosis: A Guide for the Practicing Clinician. Vol 17.
New York, NY: Springer;
2014:149-186.
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SOURCE Mallinckrodt plc