BRIDGEWATER, N.J., Jan. 4, 2021 /PRNewswire/ -- Insmed
Incorporated (Nasdaq: INSM), a global biopharmaceutical company on
a mission to transform the lives of patients with serious and rare
diseases, today announced that the first patient was dosed in
late December, 2020, in the frontline clinical trial program of
ARIKAYCE® (amikacin liposome inhalation suspension) in
patients with nontuberculous mycobacterial (NTM) lung disease
caused by Mycobacterium avium complex (MAC). The program
consists of ARISE, an interventional study designed to validate
cross-sectional and longitudinal characteristics of
patient-reported outcome (PRO) tools in MAC lung disease, and
ENCORE, a pivotal trial designed to establish, using the PRO tools
validated in the ARISE trial, the clinical benefits and evaluate
the safety of ARIKAYCE in patients with newly diagnosed MAC lung
disease.
ARIKAYCE was granted accelerated approval by the U.S. Food and
Drug Administration (FDA) in September of 2018 for the treatment of
MAC lung disease as part of a combination antibacterial drug
regimen for adult patients who have limited or no alternative
treatment options. It is the first and only therapy approved in the
U.S. for the treatment of MAC lung disease. The frontline clinical
trial program is intended to fulfill the FDA's post-marketing
requirement to allow for full approval of ARIKAYCE in the U.S. and
to support a supplemental new drug application (sNDA) for the use
of ARIKAYCE as a frontline treatment for patients with MAC lung
disease.
"We are very pleased to initiate the frontline clinical
development program for ARIKAYCE, potentially laying the groundwork
for a new standard of care for patients with MAC lung disease,"
said Martina Flammer, M.D., MBA,
Chief Medical Officer of Insmed. "ARIKAYCE has already changed the
treatment landscape of refractory MAC lung disease since its FDA
approval more than two years ago, and we are excited to build on
that foundation with the initiation of these studies. Our hope is
that this program will not only provide pivotal data for ARIKAYCE
in a frontline setting, but also will validate PRO tools for the
assessment of treatment benefit in clinical trials of patients with
MAC lung disease going forward."
ARISE is a randomized, double-blind, placebo-controlled Phase
3b study in adult patients with newly
diagnosed MAC lung disease that aims to generate evidence
demonstrating the domain specification, reliability, validity, and
responsiveness of PRO-based scores. Patients will be randomized 1:1
to receive ARIKAYCE plus background regimen or placebo plus
background regimen once daily for six months. Patients will then
discontinue all study treatments and remain in the trial for one
month for the continued assessment of PRO endpoints. The study is
expected to enroll approximately 100 patients.
ENCORE is a randomized, double-blind, placebo-controlled phase
3b study to evaluate the efficacy and
safety of an ARIKAYCE-based regimen in patients with newly
diagnosed MAC lung disease. Patients will be randomized 1:1 to
receive ARIKAYCE plus background regimen or placebo plus background
regimen once daily for 12 months. Patients will then discontinue
all study treatments and remain in the trial for three months for
the assessment of durability of culture conversion. The primary
endpoint is change from Baseline to Month 13 in respiratory
symptom score. The key secondary endpoint is the proportion of
subjects achieving durable culture conversion at Month 15. ENCORE
is expected to enroll approximately 250 patients.
Approximately 150 sites are expected to be initiated globally
for the ARISE and ENCORE clinical trials.
More information on these studies is available at
clinicaltrials.gov (ARISE: NCT04677543; ENCORE: NCT04677569).
About ARIKAYCE
ARIKAYCE is approved in the United
States as ARIKAYCE® (amikacin liposome inhalation
suspension) and in the EU as ARIKAYCE® Liposomal 590 mg
Nebuliser Dispersion. Current international treatment guidelines
recommend the use of ARIKAYCE for appropriate patients. ARIKAYCE is
a novel, inhaled, once-daily formulation of amikacin, an
established antibiotic that was historically administered
intravenously and associated with severe toxicity to hearing,
balance, and kidney function. Insmed's proprietary
PULMOVANCE® liposomal technology enables the delivery of
amikacin directly to the lungs, where liposomal amikacin is taken
up by lung macrophages where the infection resides, while limiting
systemic exposure. ARIKAYCE is administered once daily using the
Lamira® Nebulizer System manufactured by PARI
Pharma GmbH (PARI).
About PARI Pharma and the Lamira® Nebulizer
System
ARIKAYCE is delivered by a novel inhalation device, the
Lamira® Nebulizer System, developed by PARI.
Lamira® is a quiet, portable nebulizer that enables
efficient aerosolization of ARIKAYCE via a vibrating, perforated
membrane. Based on PARI's 100-year history working with aerosols,
PARI is dedicated to advancing inhalation therapies by developing
innovative delivery platforms and new pharmaceutical formulations
that work together to improve patient care.
IMPORTANT SAFETY INFORMATION FOR ARIKAYCE IN THE
U.S.
WARNING: RISK OF
INCREASED RESPIRATORY ADVERSE REACTIONS
ARIKAYCE has been associated with an increased risk of respiratory
adverse reactions,
including hypersensitivity pneumonitis, hemoptysis, bronchospasm,
and exacerbation of
underlying pulmonary disease that have led to hospitalizations in
some cases.
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Hypersensitivity Pneumonitis has been reported with the
use of ARIKAYCE in the clinical trials. Hypersensitivity
pneumonitis (reported as allergic alveolitis, pneumonitis,
interstitial lung disease, allergic reaction to ARIKAYCE) was
reported at a higher frequency in patients treated with ARIKAYCE
plus background regimen (3.1%) compared to patients treated with a
background regimen alone (0%). Most patients with hypersensitivity
pneumonitis discontinued treatment with ARIKAYCE and received
treatment with corticosteroids. If hypersensitivity pneumonitis
occurs, discontinue ARIKAYCE and manage patients as medically
appropriate.
Hemoptysis has been reported with the use of ARIKAYCE in
the clinical trials. Hemoptysis was reported at a higher frequency
in patients treated with ARIKAYCE plus background regimen (17.9%)
compared to patients treated with a background regimen alone
(12.5%). If hemoptysis occurs, manage patients as medically
appropriate.
Bronchospasm has been reported with the use of
ARIKAYCE in the clinical trials. Bronchospasm (reported as asthma,
bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea
exertional, prolonged expiration, throat tightness, wheezing) was
reported at a higher frequency in patients treated with ARIKAYCE
plus background regimen (28.7%) compared to patients treated
with a background regimen alone (10.7%). If bronchospasm occurs
during the use of ARIKAYCE, treat patients as medically
appropriate.
Exacerbations of underlying pulmonary disease has
been reported with the use of ARIKAYCE in the clinical trials.
Exacerbations of underlying pulmonary disease (reported as chronic
obstructive pulmonary disease (COPD), infective exacerbation of
COPD, infective exacerbation of bronchiectasis) have been reported
at a higher frequency in patients treated with ARIKAYCE plus
background regimen (14.8%) compared to patients treated with
background regimen alone (9.8%). If exacerbations of
underlying pulmonary disease occur during the use of ARIKAYCE,
treat patients as medically appropriate.
Anaphylaxis and Hypersensitivity Reactions: Serious
and potentially life-threatening hypersensitivity reactions,
including anaphylaxis, have been reported in patients taking
ARIKAYCE. Signs and symptoms include acute onset of skin and
mucosal tissue hypersensitivity reactions (hives, itching,
flushing, swollen lips/tongue/uvula), respiratory difficulty
(shortness of breath, wheezing, stridor, cough), gastrointestinal
symptoms (nausea, vomiting, diarrhea, crampy abdominal pain), and
cardiovascular signs and symptoms of anaphylaxis (tachycardia, low
blood pressure, syncope, incontinence, dizziness). Before therapy
with ARIKAYCE is instituted, evaluate for previous hypersensitivity
reactions to aminoglycosides. If anaphylaxis or a hypersensitivity
reaction occurs, discontinue ARIKAYCE and institute appropriate
supportive measures.
Ototoxicity has been reported with the use of ARIKAYCE in
the clinical trials. Ototoxicity (including deafness, dizziness,
presyncope, tinnitus, and vertigo) were reported with a higher
frequency in patients treated with ARIKAYCE plus background regimen
(17%) compared to patients treated with background
regimen alone (9.8%). This was primarily driven by tinnitus
(7.6% in ARIKAYCE plus background regimen vs 0.9% in the background
regimen alone arm) and dizziness (6.3% in ARIKAYCE plus background
regimen vs 2.7% in the background regimen alone arm). Closely
monitor patients with known or suspected auditory or vestibular
dysfunction during treatment with ARIKAYCE. If ototoxicity occurs,
manage patients as medically appropriate, including potentially
discontinuing ARIKAYCE.
Nephrotoxicity was observed during the clinical
trials of ARIKAYCE in patients with MAC lung disease but not at a
higher frequency than background regimen alone. Nephrotoxicity has
been associated with the aminoglycosides. Close monitoring of
patients with known or suspected renal dysfunction may be needed
when prescribing ARIKAYCE.
Neuromuscular Blockade: Patients with neuromuscular
disorders were not enrolled in ARIKAYCE clinical trials. Patients
with known or suspected neuromuscular disorders, such as myasthenia
gravis, should be closely monitored since aminoglycosides may
aggravate muscle weakness by blocking the release of acetylcholine
at neuromuscular junctions.
Embryo-Fetal Toxicity: Aminoglycosides can cause
fetal harm when administered to a pregnant woman. Aminoglycosides,
including ARIKAYCE, may be associated with total, irreversible,
bilateral congenital deafness in pediatric patients exposed in
utero. Patients who use ARIKAYCE during pregnancy, or become
pregnant while taking ARIKAYCE should be apprised of the potential
hazard to the fetus.
Contraindications: ARIKAYCE is contraindicated in
patients with known hypersensitivity to any aminoglycoside.
Most Common Adverse Reactions: The most common adverse
reactions in Trial 1 at an incidence ≥5% for patients using
ARIKAYCE plus background regimen compared to patients treated with
background regimen alone were dysphonia (47% vs 1%), cough (39% vs
17%), bronchospasm (29% vs 11%), hemoptysis (18% vs 13%),
ototoxicity (17% vs 10%), upper airway irritation (17% vs 2%),
musculoskeletal pain (17% vs 8%), fatigue and asthenia (16% vs
10%), exacerbation of underlying pulmonary disease (15% vs 10%),
diarrhea (13% vs 5%), nausea (12% vs 4%), pneumonia (10% vs 8%),
headache (10% vs 5%), pyrexia (7% vs 5%), vomiting (7% vs 4%), rash
(6% vs 2%), decreased weight (6% vs 1%), change in sputum (5% vs
1%), and chest discomfort (5% vs 3%).
Drug Interactions: Avoid concomitant use of ARIKAYCE
with medications associated with neurotoxicity, nephrotoxicity, and
ototoxicity. Some diuretics can enhance aminoglycoside toxicity by
altering aminoglycoside concentrations in serum and tissue. Avoid
concomitant use of ARIKAYCE with ethacrynic acid, furosemide, urea,
or intravenous mannitol.
Overdosage: Adverse reactions specifically associated
with overdose of ARIKAYCE have not been identified. Acute
toxicity should be treated with immediate withdrawal of ARIKAYCE,
and baseline tests of renal function should be undertaken.
Hemodialysis may be helpful in removing amikacin from the body. In
all cases of suspected overdosage, physicians should contact the
Regional Poison Control Center for information about effective
treatment.
U.S. INDICATION
LIMITED POPULATION: ARIKAYCE® is
indicated in adults, who have limited or no alternative treatment
options, for the treatment of Mycobacterium
avium complex (MAC) lung disease as part of a combination
antibacterial drug regimen in patients who do not achieve negative
sputum cultures after a minimum of 6 consecutive months of a
multidrug background regimen therapy. As only limited clinical
safety and effectiveness data for ARIKAYCE are currently available,
reserve ARIKAYCE for use in adults who have limited or no
alternative treatment options. This drug is indicated for
use in a limited and specific population of patients.
This indication is approved under accelerated approval based
on achieving sputum culture conversion (defined as 3 consecutive
negative monthly sputum cultures) by Month 6. Clinical benefit has
not yet been established. Continued approval for this indication
may be contingent upon verification and description of clinical
benefit in confirmatory trials.
Limitation of Use: ARIKAYCE has only been studied
in patients with refractory MAC lung disease defined as patients
who did not achieve negative sputum cultures after a minimum of 6
consecutive months of a multidrug background regimen therapy. The
use of ARIKAYCE is not recommended for patients with non-refractory
MAC lung disease.
Patients are encouraged to report negative side effects of
prescription drugs to the FDA.
Visit www.fda.gov/medwatch, or call 1–800–FDA–1088. You
can also call the Company at 1-844-4-INSMED.
Please see Full Prescribing
Information.
About Insmed
Insmed Incorporated is a global biopharmaceutical company on a
mission to transform the lives of patients with serious and rare
diseases. Insmed's first commercial product is a first-in-disease
therapy approved in the United
States and the European Union to treat a chronic,
debilitating lung disease. The Company is also progressing a robust
pipeline of investigational therapies targeting areas of serious
unmet need, including neutrophil-mediated inflammatory diseases and
rare pulmonary disorders. Insmed is headquartered in Bridgewater, New Jersey, with a growing
footprint across Europe and in
Japan. For more information, visit
www.insmed.com.
Forward-looking Statements
This press release contains forward-looking statements that
involve substantial risks and uncertainties. "Forward-looking
statements," as that term is defined in the Private Securities
Litigation Reform Act of 1995, are statements that are not
historical facts and involve a number of risks and uncertainties.
Words herein such as "may," "will," "should," "could," "would,"
"expects," "plans," "anticipates," "believes," "estimates,"
"projects," "predicts," "intends," "potential," "continues," and
similar expressions (as well as other words or expressions
referencing future events, conditions or circumstances) may
identify forward-looking statements.
The forward-looking statements in this press release are based
upon the Company's current expectations and beliefs, and involve
known and unknown risks, uncertainties and other factors, which may
cause the Company's actual results, performance and achievements
and the timing of certain events to differ materially from the
results, performance, achievements or timing discussed, projected,
anticipated or indicated in any forward-looking statements. Such
risks, uncertainties and other factors include, among others, the
following: failure to obtain, or delays in obtaining, regulatory
approvals for ARIKAYCE outside the U.S. or European Union or for
the Company's product candidates in the
U.S., Europe, Japan or other markets, including the
United Kingdom as a result of the
United Kingdom's exit from the
European Union; failure to successfully commercialize ARIKAYCE, the
Company's only approved product, in the
United States or European Union (amikacin liposome
inhalation suspension and Liposomal 590 mg Nebuliser Dispersion,
respectively), or to maintain U.S. or EU approval for ARIKAYCE;
business or economic disruptions due to catastrophes or other
events, including natural disasters or public health crises; impact
of the novel coronavirus (COVID-19) pandemic and efforts to reduce
its spread on the Company's business, employees, including key
personnel, patients, partners and suppliers; the risk that
brensocatib does not prove to be effective or safe for patients in
ongoing and future clinical studies, including the ASPEN and STOP-COVID19 studies; uncertainties
in the degree of market acceptance of ARIKAYCE by physicians,
patients, third-party payors and others in the healthcare
community; the Company's inability to obtain full approval of
ARIKAYCE from the FDA, including the risk that the Company will not
timely and successfully complete the study to validate a PRO tool
and the confirmatory post-marketing clinical trial required for
full approval of ARIKAYCE; inability of the Company, PARI or the
Company's other third-party manufacturers to comply with regulatory
requirements related to ARIKAYCE or the
Lamira® Nebulizer System; the Company's inability
to obtain adequate reimbursement from government or third-party
payors for ARIKAYCE or acceptable prices for ARIKAYCE; development
of unexpected safety or efficacy concerns related to ARIKAYCE or
the Company's product candidates; inaccuracies in the Company's
estimates of the size of the potential markets for ARIKAYCE or its
product candidates or in data the Company has used to identify
physicians, expected rates of patient uptake, duration of expected
treatment, or expected patient adherence or discontinuation rates;
the Company's inability to create an effective direct sales and
marketing infrastructure or to partner with third parties that
offer such an infrastructure for distribution of ARIKAYCE or any of
the Company's product candidates that are approved in the future;
failure to obtain regulatory approval to expand ARIKAYCE's
indication to a broader patient population; failure to successfully
conduct future clinical trials for ARIKAYCE, brensocatib,
treprostinil palmitil inhalation powder (TPIP) and the Company's
other product candidates due to the Company's limited experience in
conducting preclinical development activities and clinical trials
necessary for regulatory approval and its potential inability to
enroll or retain sufficient patients to conduct and complete the
trials or generate data necessary for regulatory approval, among
other things; risks that the Company's clinical studies will be
delayed or that serious side effects will be identified during drug
development; failure of third parties on which the Company is
dependent to manufacture sufficient quantities of ARIKAYCE or the
Company's product candidates for commercial or clinical needs, to
conduct the Company's clinical trials, or to comply with the
Company's agreements or laws and regulations that impact the
Company's business or agreements with the Company; the Company's
inability to attract and retain key personnel or to effectively
manage the Company's growth; the Company's inability to adapt to
its highly competitive and changing environment; the Company's
inability to adequately protect its intellectual property rights or
prevent disclosure of its trade secrets and other proprietary
information and costs associated with litigation or other
proceedings related to such matters; restrictions or other
obligations imposed on the Company by its agreements related to
ARIKAYCE or the Company's product candidates, including its license
agreements with PARI and AstraZeneca AB, and failure of the Company
to comply with its obligations under such agreements; the cost and
potential reputational damage resulting from litigation to which
the Company is or may become a party, including product liability
claims; the Company's limited experience operating internationally;
changes in laws and regulations applicable to the Company's
business, including any pricing reform, and failure to comply with
such laws and regulations; inability to repay the Company's
existing indebtedness and uncertainties with respect to the
Company's ability to access future capital; and delays in the
execution of plans to build out an additional third-party
manufacturing facility approved by the appropriate regulatory
authorities and unexpected expenses associated with those
plans.
The Company may not actually achieve the results, plans,
intentions or expectations indicated by the Company's
forward-looking statements because, by their nature,
forward-looking statements involve risks and uncertainties because
they relate to events and depend on circumstances that may or may
not occur in the future. For additional information about the risks
and uncertainties that may affect the Company's business, please
see the factors discussed in Item 1A, "Risk Factors," in the
Company's Annual Report on Form 10-K for the year
ended December 31, 2019, the Company's Quarterly Reports on
Form 10-Q for the quarters ended March 31, 2020, June 30, 2020 and September 30, 2020, and any subsequent Company
filings with the Securities and Exchange Commission (SEC).
The Company cautions readers not to place undue reliance on any
such forward-looking statements, which speak only as of the date of
this press release. The Company disclaims any obligation, except as
specifically required by law and the rules of the SEC, to publicly
update or revise any such statements to reflect any change in
expectations or in events, conditions or circumstances on which any
such statements may be based, or that may affect the likelihood
that actual results will differ from those set forth in the
forward-looking statements.
Contact:
Investors:
Argot Partners
Laura Perry or Heather Savelle
(212) 600-1902
Insmed@argotpartners.com
Media:
Mandy Fahey
Senior Director, Corporate Communications
Insmed
(732) 718-3621
amanda.fahey@insmed.com
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