STAINES-UPON-THAMES, United
Kingdom, March 4, 2020
/PRNewswire/ -- Mallinckrodt
plc (NYSE: MNK), a global biopharmaceutical company, today
announced findings from a retrospective medical record analysis to
assess practice patterns and outcomes of Acthar® Gel
(repository corticotropin injection) in the treatment of the
immune-mediated diseases rheumatoid arthritis (RA), systemic lupus
erythematosus (SLE) and dermatomyositis/polymyositis (DM/PM).
Results of the study were recently published online in Open
Access Rheumatology: Research and Reviews.
Acthar Gel is a naturally sourced complex mixture of
adrenocorticotropic hormone analogs and other pituitary peptides.
Acthar Gel is approved by the U.S. Food and Drug Administration
(FDA) as adjunctive therapy for short-term administration (to tide
the patient over an acute episode or exacerbation) in RA, including
juvenile RA (selected cases may require low-dose maintenance
therapy), and for use during an exacerbation or as maintenance
therapy in selected cases of: systemic lupus erythematosus,
systemic dermatomyositis (polymyositis).1 Please
see Important Safety Information for Acthar Gel below.
The study, titled "Treatment with Repository Corticotropin
Injection in Patients with Rheumatoid Arthritis, Systemic Lupus
Erythematosus, and Dermatomyositis/Polymyositis," examined 92 adult
patients (≥18 years of age) – 54 with RA, 30 with SLE and 8 with
DM/PM – who were treated at 14 U.S. clinical sites with Acthar Gel
between January 1, 2011 and
February 15, 2016. Researchers
collected data on patient demographics, disease and treatment
history; Acthar Gel dosing, frequency and duration; concomitant
medication use; and physicians' assessments of outcomes and adverse
events. Results of the analysis showed that across all three
patient populations, the most frequently reported reasons for
initiating treatment with Acthar Gel were inadequate response to
prior therapies, acute exacerbation or flare of disease, and need
for an alternative therapy. The findings also suggest that
patients' symptoms improved with Acthar Gel as reported by
physicians' impression of overall change after treatment initiation
and over the course of the study. Among 57 patients with data on
physician impression of change, 78.1 percent of patients with RA,
94.7 percent of patients with SLE and 66.7 percent of patients with
DM/PM had a rating of improved. Further, the mean time to best
impression of change was 3.4±2.5 months for RA, 4.3±2.7 for SLE,
and 3.4±1.6 for DM/PM.
"All three immune-mediated diseases examined in this study can
be difficult to manage, and patients can often experience
debilitating disease flares and exacerbations," said
Tunde Otulana, M.D., Senior Vice
President and Chief Medical Officer at Mallinckrodt. "The study suggests that Acthar
Gel may have been associated with an improvement in disease
exacerbations and symptoms, and it provides insights into
real-world practice patterns and outcomes associated with Acthar
Gel therapy that may help inform decision-making among clinicians
in managing these conditions."
Further, the study builds on the company's Phase 4 study of
Acthar Gel in RA patients (open-label portion, n=259; randomized,
placebo-controlled, blinded, withdrawal portion, n=154) presented
at the European Congress of Rheumatology 2019 (EULAR), June 12-15 in Madrid. The randomized, placebo-controlled,
double-blind two-part study demonstrated that significantly more
patients with persistently active RA who met response criteria at
week 12 (63 percent of patients in the open-label period who
achieved low disease activity (LDA) as assessed by Disease Activity
Score 28-joint count Erythrocyte Sedimentation Rate (DAS28-ESR) of
<3.2 at 12 weeks) maintained LDA with Acthar Gel (62 percent)
versus placebo (43 percent, P<0.05) at week 24. In the
double-blind period of the study (weeks 12-24), adverse events
(AEs) were reported in 33 percent of the Acthar Gel treatment group
and 40 percent of the placebo group. In the open-label period of
the study (weeks 0-12), AEs were reported in 38 percent of
patients. Overall AEs observed in the study were consistent with
previous trials of Acthar Gel. The study was subject to study
limitations, including that the results may not be solely
attributable to Acthar Gel.
Key Findings:2
- Data were collected from 92 patients (54 with RA; 30 with SLE;
8 with DM/PM) with mean age of over 49 years who were predominately
female. Data collection spanned the 12 months prior to and up to 12
months following initiation of Acthar Gel treatment.
- Prior to treatment with Acthar Gel, most patients had been
treated with multiple therapies, including the most common
therapies, which were as follows:
-
- Patients with RA:
-
- 94 percent non-biologic disease-modifying antirheumatic drugs
(DMARDs)
- 87 percent corticosteroids
- 87 percent biologic DMARDS
- Patients with SLE:
-
- 80 percent corticosteroids
- 73 percent nonbiologic DMARDs
- 57 percent immunosuppressive drugs
- Patients with DM/PM:
-
- 88 percent immunosuppressive drugs
- 75 percent corticosteroids
- In all three populations, the most common starting dose of
Acthar Gel was 80 U twice weekly, which was used for 84 percent of
RA patients, 75 percent of SLE patients, and 86 percent of DM/PM
patients.
- Changes in Acthar Gel dose occurred in 33 percent of patients
with RA, 43 percent of patients with SLE, and 25 percent of
patients with DM/PM.
- The usual dose of Acthar Gel is 40-80 units given
intramuscularly or subcutaneously every 24-72 hours.
- The mean duration of treatment was:
-
- 4.8 months in RA
- 6.5 months in SLE
- 6.8 months in DM/PM
- Among the 57 patients with data on physicians' impression of
change (n=32; 59 percent with RA, n=19; 63 percent with SLE, and
n=6; 75 percent with DM/PM), physicians rated their impression of
change as improved in 78.1 percent of patients with RA; 94.7
percent of patients with SLE; and 66.7 percent of patients with
DM/PM.
- Adverse events were reported in 14 patients (26 percent) with
RA; 5 patients with SLE (17 percent); and 2 patients with DM/PM (25
percent). Serious adverse events were reported in 1 patient with RA
(2 percent); 4 patients with SLE (13 percent); and 1 patient with
DM/PM (12 percent).
- Acthar Gel treatment was discontinued in 24 (44 percent) RA
patients, 6 (20 percent) SLE patients, and 5 (63 percent) DM/PM
patients. The most common reasons for discontinuation of Acthar Gel
were reported as:
-
- Patients with RA:
-
- AEs related to Acthar Gel (38 percent)
- Disease resolution/remission/treatment no longer necessary (17
percent)
- Physician choice (17 percent)
- Patients with SLE:
-
- Treatment-related AEs (50 percent)
- Patients with DM/PM:
-
- AEs related to Acthar Gel (40 percent)
- Lack of efficacy/inadequate response/disease progression (40
percent)
Study Limitations:2
- The study is limited by its retrospective design, small sample
size and reliance on medical records, some of which had missing
data and may have had errors and omissions (such as care received
at other clinics).
- Disease activity is difficult to assess through medical
records, as it is not routinely recorded or recorded with the
appropriate timing to allow evaluation of clinical response to
therapy.
- Utilization of physicians' impression of change as a
descriptive endpoint was a subjective measure relying on an
individual clinician's own standards of improvement and was not
available for 38 percent of the records evaluated.
- The study's retrospective noncomparative design did not allow
researchers to determine if patients were responding to other
therapies.
- Results are exploratory and should be interpreted with these
limitations in mind.
- Results may not be solely attributable to Acthar Gel.
The study was funded by Mallinckrodt.
About Rheumatoid Arthritis
RA is an autoimmune
disease. It is a chronic condition that causes pain, stiffness, and
swelling of the joints—all symptoms and signs caused by
inflammation.3 An estimated 1.5 million U.S. adults are
living with RA.4 Treatment is aimed at stopping
inflammation to put the disease in remission and relieve
symptoms.5 Nonsteroidal anti-inflammatory drugs are used
to ease symptoms whereas corticosteroids, disease-modifying
anti-rheumatic drugs and biologics are used to slow down the
disease activity.5
About Systemic Lupus Erythematosus
SLE is an
autoimmune disease in which the immune system produces antibodies
to cells within the body leading to widespread inflammation and
tissue damage.6 It is the most common form of lupus, a
condition that impacts an estimated 1.5 million
Americans.7 Ninety percent of those diagnosed with lupus
are women, often between the ages of 15-44.8 Lupus is
characterized by periods of illness "flares" and remissions and the
disease can affect the joints, skin, brain, lungs, kidneys, and
blood vessels. Symptoms and signs may include fatigue, pain or
swelling in joints, skin rashes, and fevers.6
About Dermatomyositis/Polymyositis
DM/PM are rare
inflammatory diseases that cause progressive muscle
weakness.9 For instance, muscle weakness associated with
PM involves those in the hips, thighs, shoulders, upper arms and
neck.10 DM also causes skin rashes.9 People
of all ages can be affected, though it usually occurs in adults
between the ages of 45-60 and is more common in
women.11,[12]
Acthar Gel (repository corticotropin injection)
Indications
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
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 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-2000329 03/20
References
1 Acthar® Gel (repository corticotropin injection)
[prescribing information]. Mallinckrodt ARD LLC.
2 Ho-Mahler N, Turner B, Eaddy M, Hanke ML, Nelson
WW. Treatment with repository corticotropin injection in patients
with rheumatoid arthritis, systemic lupus erythematosus, and
dermatomyositis/polymyositis. Open Access Rheumatology: Research
and Reviews. 2020:12 21-29.
3 Mayo Clinic website. Rheumatoid Arthritis.
Overview. Available at:
https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648.
Accessed November 5, 2019.
4 Arthritis Foundation. What is Rheumatoid
Arthritis? Available at:
http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/what-is-rheumatoid-arthritis.php.
Accessed November 5, 2019.
5 Arthritis Foundation. Rheumatoid Arthritis
Treatment. Available at:
http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/treatment.php.
Accessed November 5, 2019.
6 The Centers for Disease Control and Prevention.
Systemic lupus erythematosus (SLE or lupus). Available at:
https://www.cdc.gov/lupus/facts/detailed.html. Accessed
March 21, 2019.
7 Kabadi S, Yeaw J, Bacani AK, Tafesse E, Bos K,
Karkare S, et al. Healthcare resource utilization and costs
associated with long-term corticosteroid exposure in patients with
systemic lupus erythematosus. Lupus. 2018;27:1799-1809. doi:
10.1177/0961203318790675.
8 Pons-Estel GJ, Alarcon GS, Scofield L, Reinlib L,
Cooper GS. Understanding the epidemiology and progression of
systemic lupus erythematosus. Semin Arthritis Rheum. 2010;
39(4):257–268.
9 Medline Plus. Myositis.
https://medlineplus.gov/myositis.html. Accessed November 3, 2016.
10 Mayo Clinic. Polymyositis.
http://www.mayoclinic.org/diseases-conditions/polymyositis/basics/symptoms/con-20020710.
Accessed November 3, 2016.
11 Bernatsky S, Joseph L, Pineau CA, et al.
Estimating the prevalence of polymyositis and dermatomyositis from
administrative data: age, sex and regional differences. Ann
Rheum Dis. 2009;68:1192-1196.
12 Cheeti A, Panginikkod S. Dermatomyositis and
Polymyositis. [Updated 2019 Nov 13]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls
Publishing; 2020 Jan-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK532860/.
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