STAINES-UPON-THAMES, United
Kingdom, Dec. 16, 2019
/PRNewswire/ -- Mallinckrodt plc
(NYSE: MNK), a global biopharmaceutical company, today confirmed
enrollment of the first patient in the company's Phase 4,
multi-center, multiple-dose, open-label study to assess the effects
of Acthar Gel as a therapy option in patients with severe
keratitis1.
"In my experience, a considerable number of severe keratitis
patients can have persistent disease that may not be resolved by
first-line treatment," said Eugene
McLaurin, MD and Fellow, American Academy of Ophthalmology
and American College of Surgeons. "I am pleased that the first
patient has been enrolled in this important Phase 4 study, the
results of which may potentially provide data to further support
Acthar Gel as a treatment option in appropriate keratitis
patients."
Acthar Gel is approved by the U.S. Food and Drug Administration
(FDA) for the 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 – one of the product's 19 indications. Please see
Important Safety Information below.
"The enrollment of the first patient in this study is an
important milestone in our assessment of Acthar's efficacy as a
treatment option for patients with keratitis," said Tunde Otulana, M.D., Chief Medical Officer at
Mallinckrodt. "We believe this
exploratory evaluation of patients whose severe keratitis persists
– after the use of one or more standard treatments – can
potentially help physicians better understand which individuals may
benefit from the drug as a treatment alternative."
About the Trial
The Phase 4 clinical study is titled
"A Multicenter, Open-Label Study to Assess the Efficacy and Safety
of Acthar Gel in Subjects with Severe Keratitis." This is a Phase
4, multicenter, multiple dose, open label study to examine the
effects of Acthar in adult subjects, with a target enrollment of
30. Subjects with current severe keratitis who meet entry criteria
will be treated with Acthar Gel 1 mL (80 units [U]) subcutaneously
(SC) two times per week for 12 weeks. Initial treatment will be
followed by a taper to Acthar 1 mL (80 U) SC once a week for two
weeks, then 0.5 mL (40 U) SC once a week for two
weeks1.
Response will be evaluated by determining the proportion of
patients who improved on the Impact of Dry Eye on Everyday Life
scale (time frame: from baseline to 12 weeks) and the proportion of
subjects who show improvement from baseline in the IDEEL symptom
bother score at 12 weeks1.
Full study details can be found on clinicaltrials.gov.
About Severe Keratitis
Keratitis is a painful
inflammation of the cornea which can result in partial or total
loss of vision if left untreated and is a significant cause of
ocular morbidity around the world.2 It can result
from infectious agents (e.g., microbes including bacteria, fungi,
amebae, and viruses) or from noninfectious causes (e.g., eye
trauma, chemical exposure, and ultraviolet
exposure).3 Conditions that affect the integrity of
the ocular surface epithelium (exposure keratitis, neurotrophic
keratitis, keratomalacia, recurrent corneal erosions) may also lead
to development of sterile corneal
ulcers.4 Non-infectious corneal ulcers may be
associated with various collagen vascular or other autoimmune
diseases, sometimes as the presenting sign of the
disease.3
About 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)
- 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)
- The treatment of symptomatic sarcoidosis
- 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 with regard to the
study described in this release, as well as 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
Investor Relations
Daniel J.
Speciale, CPA
Investor Relations and Strategy Officer
314-654-3638
daniel.speciale@mnk.com
Media
Daniel Yunger
Kekst CNC
212-521-4879
mallinckrodt@kekstcnc.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-1902249 12/19
References
1 https://clinicaltrials.gov/ct2/show/NCT04169061?term=acthar&recrs=ab&cond=Keratitis&cntry=US&draw=2&rank=1
2 Sharma S. Keratitis. Bioscience Reports.
2001;21:419-444.
3 Collier SA, Gronostaj MP, MacGurn, AK, Cope
JR, Awsumb KL, Yoder JS, et al. Estimated burden of
keratitis--United States, 2010.
MMWR Morb Mortal Wkly Rep. 2014;63(45):1027–1030..
4 Donzis PB, Mondino BJ. Management of
noninfectious corneal ulcers. Surv Ophthalmol. 1987;32:94–110.
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SOURCE Mallinckrodt plc