STAINES-UPON-THAMES, United
Kingdom, Nov. 12, 2019
/PRNewswire/ -- Mallinckrodt plc (NYSE:
MNK), a global biopharmaceutical company, today announced data on
patient-reported outcomes (PROs) showing Acthar® Gel
(repository corticotropin injection) improved disease measures that
impact rheumatoid arthritis (RA) patients with persistently active
disease, as well as new data from an exploratory analysis. The
data originate from new analyses from Mallinckrodt's Phase 4 study of Acthar Gel in
RA patients with persistently active disease and was recently
presented at the 2019 American College of Rheumatology/Association
of Rheumatology Professionals (ACR/ARP) Annual Meeting, held
Nov. 8-13 in Atlanta.
The study posters can be accessed here on the
company's website.
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).1 Please see
Important Safety Information for Acthar Gel below.
"Patient-reported outcomes, like fatigue, pain, and physical
functioning, are an important part of any trial assessing clinical
treatment outcomes. These additional data shed light on managing
this challenging patient population whose symptoms persist after
use of first-line therapies and suggest Acthar Gel treatment
improved PROs in patients with persistently active RA," said Dr.
Nancy E. Lane, Distinguished
Professor of Medicine, Rheumatology and Aging, and Director of the
UC Davis Center for Musculoskeletal Health. "The data exploring
the effect of Acthar Gel treatment on patient-reported outcomes may
help clinicians better understand Acthar Gel's use for patients
with difficult-to-manage RA, those who have continued symptoms
following standard therapies. The need for additional treatment
options in this patient population is critical."
Patient-Reported Outcomes and Impact of Treatment (Abstract
#439)
New data from the company's two-part Phase 4 multicenter,
placebo-controlled study assessing the efficacy and safety of
Acthar Gel in patients with persistently active RA who were
previously treated with disease-modifying anti-rheumatic drugs
(DMARDs) and corticosteroids showed that Acthar Gel treatment
significantly improved patient-reported pain, fatigue, physical
functioning and work-related impairment as early as Week 4, and
resulted in clinically meaningful improvements in PROs.
The analysis examined PRO measures as a secondary endpoint from
Part 1 of the study, the 12-week open-label period, and assessed
mean changes at baseline and at Weeks 4, 8 and 12.
Patient-Reported Outcomes From the 12-Week Open-label RCI
Treatment Perioda,2
PRO
Assessment
|
Baseline, Mean
(SD)
|
Week
4
|
Week
8
|
Week
12
|
Mean Change From
Baseline (SD)
|
FACIT-F
|
22.8 (8.4)
|
−5.0
(8.2)*
|
−6.5
(8.4)*
|
−8.7
(8.4)*
|
HAQ-DI
|
1.7 (0.6)
|
−0.5
(0.5)*
|
−0.6
(0.6)*
|
−0.84
(0.6)*
|
Patient global
assessment of disease
activityb,3
|
63.4
(20.0)
|
−17.8
(23.6)*
|
−25.7
(25.2)*
|
−35.0
(27.3)*
|
WPAI-RA
|
Percent work time
missed due to RAc
|
24.9
(27.6)
|
−7.0
(26.6)
|
−5.2
(28.0)
|
−10.8
(26.5)**
|
Percent impairment
while working due to RAc
|
50.3
(27.1)
|
−18.7
(24.4)*
|
−18.0
(23.9)*
|
−25.2
(25.3)*
|
Percent overall work
impairment due to RAc
|
58.1
(28.6)
|
−17.6
(27.0)*
|
−17.6
(27.5)*
|
−25.5
(29.2)*
|
Percent activity
impairment due to RAc
|
63.2
(24.2)
|
−18.1
(24.3)*
|
−22.5
(25.3)*
|
−32.8
(27.4)*
|
Patient global
assessment of paind
|
64.9
(20.4)3
|
−20.8
(23.3)*
|
−27.6
(25.3)*
|
−37.4
(27.4)*
|
*p<0.001 vs
baseline. **p=0.003 vs baseline.
|
a mITT population (all patients who
received study drug and had any post-treatment efficacy
assessment).
|
b MCID = 15% absolute/20% relative
improvement.
|
c MCID = 7% absolute
change.
|
d MCID = 11.
|
Abbreviations and
MCID references: FACIT-F; Functional Assessment of Chronic Illness
Therapy – Fatigue (MCID = 3-41); HAQ-DI, Health
Assessment Questionnaire – Disability Index (MCID = 0.2); MCID,
minimum clinically important difference; mITT, modified
intent-to-treat; PRO, patient-reported outcome; RCI, repository
corticotropin injection; SD, standard deviation; WPAI-RA, Work
Productivity and Activity Impairment Questionnaire – Rheumatoid
Arthritis.
|
AEs observed in the Phase 4 study were consistent with those in
previous trials of Acthar Gel.
Study Limitations
- Sample bias may exist for the open-label phase of the ongoing
study, and patients were aware that they were receiving Acthar
Gel.4
- Examiner bias may also exist as the patient had to reach low
disease activity in order to enter the second phase of the
study.4
- The results cannot be solely attributed to Acthar Gel since
patients were on different medications at the start of the trial
and no washout periods were undertaken.4
"Mallinckrodt remains committed to
the rheumatology community and to improving the lives of patients
with autoimmune-mediated diseases like RA who continue to have
debilitating symptoms and disease exacerbations despite standard
treatments," said Steven
Romano, M.D., Chief Scientific Officer and Executive Vice
President at Mallinckrodt. "We are pleased to be at this
year's ACR Annual Meeting to present new data on Acthar Gel that
will broaden our understanding of its utility in rheumatology
clinical practice for patients with difficult-to-manage RA and
areas of high unmet need."
Assessment of Bone and Cartilage Turnover Markers (Abstract
#528)
A new exploratory analysis from the Phase 4 RA study assessed
bone markers associated with bone loss to evaluate the impact of
Acthar Gel treatment on bone turnover in patients with persistently
active RA. Bone and cartilage biomarker levels were evaluated
throughout the study, at baseline and Weeks 12 and 24 and included:
C-terminal cross-linking telopeptide (CTX), C-terminal
cross-linking telopeptide of type I collagen (CTX-I),
osteoprotegrin (OPG), N-terminal propeptide of type I collagen
(PINP), and soluble receptor activator of nuclear factor kappa-β
ligand (sRANKL) and cartilage degradation biomarkers (C-terminal
cross-linking telopeptide of type II collagen (CTX-II) and CTX-II
creatinine (CRT).
At Week 12, the open-label period, significant decreases in mean
levels of the bone turnover biomarker PINP (P<0.01) and mean
levels of cartilage degradation biomarkers CTX-II (P<0.01) and
CTX-II CRT (P<0.001) were observed. At Week 24, the end of the
study's double-blind period, there was a significant increase from
baseline in mean sRANKL levels at both Week 12 and Week 24
(P<0.05) compared to placebo, suggesting a potential increase in
osteoclast differentiation. Mean levels of all other bone and
cartilage biomarkers remained stable at all time points and markers
of bone degeneration remained stable.5
Results from the full RA study were presented earlier this year
at the Annual European League Against Rheumatism (EULAR 2019) in
Madrid in June. More information
on the Phase 4 RA study can be found here on
ClinicalTrials.gov.
About Rheumatoid Arthritis
RA is an autoimmune disease. It is a chronic condition that causes
pain, stiffness, and swelling of the joints—all symptoms caused by
inflammation.6 An estimated 1.5 million U.S. adults are
living with RA.7 Treatment is aimed at stopping
inflammation to put the disease in remission and relieve
symptoms.8 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.8
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 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-1901844 11/19
References
|
|
|
|
|
1 Acthar® Gel
(repository corticotropin injection) [prescribing
information]. Mallinckrodt ARD LLC.
|
2 Data on File, Mallinckrodt, 2019.
Furst D, Wan G, Liu J, Zhu J, Bartels-Peculis L, Panaccio M,
Fleischmann R. Improved Patient-Reported Outcomes in Patients with
Persistently Active Rheumatoid Arthritis Following Treatment with
Repository Corticotropin Injection. Poster presented at: 2019
American College of Rheumatology/Association of Rheumatology
Professionals (ACR/ARP) Annual Meeting November 8-13, Atlanta,
GA.
|
3 Data on File, Mallinckrodt, 2019.
Furst D, Wan G, Liu J, Zhu J, Bartels-Peculis L, Panaccio M,
Fleischmann R. Improved Patient-Reported Outcomes in Patients with
Persistently Active Rheumatoid Arthritis Following Treatment with
Repository Corticotropin Injection [abstract]. Arthritis Rheumatol.
2019; 71 (suppl 10).
https://acrabstracts.org/abstract/improved-patient-reported-outcomes-in-patients-with-persistently-active-rheumatoid-arthritis-following-treatment-with-repository-corticotropin-injection/.
Accessed November 8, 2019.
|
4 Fleischmann R, Furst DE, Brasington
R, Connolly-Strong E, Liu J, Barton ME. A multicenter study
assessing the efficacy and safety of repository corticotropin
injection in patients with rheumatoid arthritis: preliminary
interim data from the open-label treatment period. Poster presented
at: American College of Rheumatology and Association of
Rheumatology Health Professionals (ACR/ARHP) Annual Meeting;
October 19-24, 2018; Chicago, IL.
|
5 Data on
File, Mallinckrodt, 2019. Fleischmann R, Furst DE, Connolly-Strong
E, Liu J, Zhu J, Brasington R. Assessment of Bone and Cartilage
Turnover Markers Following Treatment With Repository Corticotropin
Injection in Patients With Persistently Active Rheumatoid
Arthritis. Poster presented at: 2019 American College of
Rheumatology/Association of Rheumatology Professionals (ACR/ARP)
Annual Meeting November 8-13, Atlanta, GA.
|
6 Mayo
Clinic website. Rheumatoid Arthritis. Overview. Available
at: https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648.
Accessed November 5, 2019.
|
7 What is
Rheumatoid Arthritis? Arthritis Foundation. Available
at: http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/what-is-rheumatoid-arthritis.php.
Accessed November 5, 2019.
|
8
Arthritis Foundation. Rheumatoid Arthritis Treatment. Available
at: http://www.arthritis.org/about-arthritis/types/rheumatoid-arthritis/treatment.php.
Accessed November 5, 2019.
|
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