– If Approved, ARIKAYCE Will Be First and Only Therapy in the
European Union for This Difficult-to-Treat Condition –
– Decision from European Commission Expected Second Half of
2020 –
BRIDGEWATER, New Jersey,
July 24, 2020 /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
Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency has adopted a positive opinion
recommending ARIKAYCE Liposomal 590 mg Nebuliser Dispersion for the
treatment of non-tuberculous mycobacterial (NTM) lung infections
caused by Mycobacterium avium complex (MAC) in
adults with limited treatment options who do not
have cystic fibrosis. Consideration should be given to official
guidance on the appropriate use of antibacterial agents.
The European Commission (EC) will review the CHMP opinion, with
a final decision anticipated in the second half of 2020.
"Today's positive opinion from the CHMP marks an important step
in our journey to transform the way MAC lung disease is managed for
patients around the world. If approved by the EC, ARIKAYCE would be
the first therapy in both the European Union and the United States for patients with this
chronic, debilitating condition," said Will
Lewis, Chairman and Chief Executive Officer of Insmed. "We
look forward to potentially bringing ARIKAYCE to appropriate
patients in Europe as quickly as
possible."
The CHMP opinion is based on results from the Phase 3 CONVERT
study, which demonstrated that once-daily ARIKAYCE, when combined
with multi-drug regimen (MDR), improved sputum culture conversion
rates in patients with refractory NTM lung disease caused by MAC
compared to MDR therapy alone.
"The positive CHMP opinion underscores the potential benefit of
ARIKAYCE in the management of MAC lung disease for patients who are
particularly difficult to treat and continue to suffer in the
absence of an approved therapy in Europe," said Prof. Dr. Christoph Lange, Medical Director of Clinical
Infectious Diseases at the Medical Clinic of the Research Center
Borstel, Leibniz Lung Center, Germany. "As demonstrated in the Phase 3
CONVERT study, ARIKAYCE has the potential to improve
culture-conversion rates in patients with MAC lung disease who were
not responsive to standard of care—a critical milestone in the
treatment landscape of this disease."
In the United States, ARIKAYCE
(under the generic name amikacin liposome inhalation suspension),
is the first and only approved treatment for MAC lung disease as
part of a combination antibacterial drug regimen for adult patients
with limited or no alternative treatment options. Insmed has also
submitted a new drug application for ARIKAYCE in Japan for the
treatment of patients with NTM lung disease caused by MAC who did
not sufficiently respond to prior treatment. New international
treatment guidelines issued in July
2020 recommend the use of ARIKAYCE in combination with a
multidrug regimen in patients with MAC lung disease who have failed
standard therapy after at least six months of treatment.
ARIKAYCE previously received Orphan Drug Designation in the
European Union for the treatment of NTM lung infections.
About MAC Lung Disease
Mycobacterium avium complex (MAC) lung disease is a
rare and serious disorder that can significantly increase morbidity
and mortality. Patients with MAC lung disease can experience a
range of symptoms that often worsen over time, including chronic
cough, dyspnea, fatigue, fever, weight loss, and chest pain. In
some cases, MAC lung disease can cause severe, even permanent
damage to the lungs, and can be fatal. MAC lung disease is an
emerging public health concern worldwide with significant unmet
need.
About ARIKAYCE
In the United States, ARIKAYCE
is the first and only FDA-approved therapy indicated for the
treatment of Mycobacterium avium complex (MAC)
lung disease as part of a combination antibacterial drug regimen
for adult patients with limited or no alternative treatment
options. Current international treatment guidelines recommend
the use of ARIKAYCE in combination with a multidrug regimen in
patients with MAC lung disease who have failed standard therapy
after at least six months of treatment. 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).
ARIKAYCE is not approved in any country other than the United States.
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 liquid medications, including liposomal
formulations such as 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.
About CONVERT (INS-212)
CONVERT was a randomized, open-label, global Phase 3 study
designed to confirm the sputum culture conversion results seen in
Insmed's Phase 2 clinical study of ARIKAYCE in patients with
refractory NTM lung disease caused by MAC. CONVERT was conducted in
18 countries at more than 125 sites. In the U.S., the primary
efficacy endpoint was the proportion of patients who achieved
sputum culture conversion at Month 6 in the ARIKAYCE plus MDR arm
compared to the MDR-only arm. Patients who achieved sputum culture
conversion by Month 6 continued in the CONVERT study for an
additional 12 months of treatment following the first monthly
negative sputum culture. The CONVERT study also evaluated the
proportion of patients who maintained sputum culture conversion 3
months off all MAC treatment, which was the primary efficacy
endpoint in the EU.
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.
|
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,
ARIKAYCE® (amikacin liposome inhalation
suspension), is the first and only therapy approved in the
United States for the treatment of
refractory Mycobacterium avium complex (MAC) lung
disease as part of a combination antibacterial drug regimen for
adult patients with limited or no alternative treatment options.
MAC lung disease is a chronic, debilitating condition that can
cause severe and permanent lung damage. Insmed's earlier-stage
clinical pipeline includes brensocatib, a novel oral reversible
inhibitor of dipeptidyl peptidase 1 with therapeutic potential in
non-cystic fibrosis bronchiectasis and other inflammatory diseases,
and treprostinil palmitil, an inhaled formulation of a treprostinil
prodrug that may offer a differentiated product profile for rare
pulmonary disorders, including pulmonary arterial hypertension. 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 for the Company's
product candidates in the U.S., Europe, Japan or
other markets, including the United Kingdom as a result
of its recent exit from the European Union; failure to successfully
commercialize or maintain U.S. approval for ARIKAYCE, the Company's
only approved product; the risk that brensocatib does not prove
effective or safe for patients in the STOP-COVID19 study; 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 our business, employees, including key personnel,
patients, partners and suppliers; 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 complete
the confirmatory post-marketing study 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 brensocatib; inaccuracies in the
Company's estimates of the size of the potential markets for
ARIKAYCE or brensocatib 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; 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 and the Company's other
product candidates, including due to the Company's limited
experience in conducting preclinical development activities and
clinical trials necessary for regulatory approval and the Company's
inability to enroll or retain sufficient patients to conduct and
complete the trials or generate data necessary for regulatory
approval; 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 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 FDA-approved third-party manufacturing facility 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, our Quarterly Report on Form 10-Q for
the quarter ended March 31, 2020 and any subsequent
Company filings with the 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
Logo -
https://mma.prnewswire.com/media/801462/Insmed_Logo.jpg