Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical
company focused on the unmet needs of patients with rare diseases,
today announced that the Company presented data at IDWeek 2018 and
at the CHEST Annual Meeting that provide additional insight into
Mycobacterium avium complex (MAC) lung disease, a chronic and
debilitating condition that can significantly increase patient
morbidity and mortality. The Company also presented additional data
from clinical trials of ARIKAYCE® (amikacin liposome inhalation
suspension), the first and only therapy approved in the U.S. 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. ARIKAYCE received accelerated
approval from the U.S. Food and Drug Administration (FDA) on
September 28, 2018.
“The data presented at IDWeek and CHEST add to the growing body
of research surrounding MAC lung disease and reaffirm our
understanding that this is a serious disease associated with
significantly increased mortality,” said Paul Streck, M.D., Chief
Medical Officer of Insmed. “We are very pleased that with the
recent FDA approval of ARIKAYCE, patients with MAC lung disease who
are refractory to the current standard of care now have an approved
treatment available. We are committed to gleaning additional data
from the ongoing CONVERT clinical trial program as well as
conducting a clinical study to support full approval of
ARIKAYCE.”
The following data were presented at IDWeek 2018,
October 3-7 in San Francisco:
All-cause Mortality Increased with Nontuberculous Mycobacterial
Lung Disease in US Medicare Beneficiaries
In this oral presentation on October 4, researchers shared
results from a database analysis assessing the rate and risk
factors of all-cause mortality in Medicare beneficiaries with
nontuberculous mycobacterial (NTM) lung disease. Researchers
reported that within Medicare Part A and B programs between 2008
and 2015, all-cause mortality was two times higher among patients
with NTM lung disease compared with age- and sex-matched controls.
When adjusted for comorbidities, patients with NTM lung disease had
a 1.3 times higher death rate than controls.
Incidence and Prevalence of Nontuberculous Mycobacterial Lung
Disease in US Medicare Beneficiaries, 2008-2015
In this poster presentation on October 4, researchers reported
results from an investigation to evaluate the incidence and
prevalence of NTM lung disease among Medicare Part A and B
beneficiaries. The study demonstrated that incidence increased from
2008 through 2013 and leveled off in more recent years, while
prevalence continued to rise through 2015. Incidence and prevalence
were higher in females than in males, and higher in Asian than in
other races/ethnicities.
Amikacin Liposome Inhalation Suspension (ALIS) Add-on Therapy
for Refractory Mycobacterium avium Complex (MAC) Lung Disease:
Effect of In Vitro Amikacin Susceptibility on Sputum Culture
Conversion
In a poster presentation on October 4, researchers reported the
results of a post-hoc analysis of the Phase 3 CONVERT (INS-212)
study to evaluate the impact of amikacin susceptibility on culture
conversion outcomes in the study. CONVERT is an ongoing randomized,
open-label comparison of ARIKAYCE plus guideline-based therapy
(GBT) with GBT alone in patients with treatment-refractory MAC lung
disease.
Researchers reported that at baseline, amikacin minimum
inhibitory concentrations (MIC), the lowest concentration of
amikacin that inhibits MAC growth, were similar across treatment
arms and across evaluated geographic regions. The percentage of
patients achieving culture conversion was similar for patients who
had MAC isolates with amikacin MIC values ranging from 8 μg/mL to
64 μg/mL. Additionally, conversion rates were similar for patients
with M. avium and M. intracellulare, and across geographic regions
studied in CONVERT. MAC isolates with postbaseline amikacin MIC
> 64 μg/mL were found in 7.7% of patients and were associated
with low culture conversion rates; no patients with concurrent
macrolide resistance achieved culture conversion.
The following data were presented at the CHEST Annual
Meeting, October 6-10 in San Antonio:
Relationship Between In Vitro Clarithromycin Susceptibility and
Sputum Culture Conversion with Add-on Amikacin Liposome Inhalation
Suspension (ALIS) for Treatment of Refractory Mycobacterium avium
Complex (MAC) Lung Disease
In this oral presentation on October 8, researchers reported
results from a post-hoc analysis of MAC species epidemiology,
macrolide susceptibility, and relationship to culture conversion in
the CONVERT study. Results demonstrated regional differences in MAC
species and macrolide susceptibility at baseline, with higher
prevalence of M. avium and higher rates of macrolide resistance in
Japan compared with other regions assessed. Researchers also
reported that culture conversion was numerically higher in the
ARIKAYCE plus GBT group compared with the GBT-alone group across
MAC species and geographic regions. Overall, culture conversion was
numerically lower among patients with macrolide resistance.
“The susceptibility analyses presented at IDWeek and CHEST
provide important insight into how susceptibility testing can help
guide treatment decisions for patients with MAC lung disease,” said
David Griffith, M.D., Professor of Medicine, W.A. and E.B. Moncrief
Distinguished Professor at The University of Texas Health Science
Center. “Importantly, the general trends of both analyses suggest
that patients treated with ARIKAYCE plus GBT had better
culture-conversion outcomes than patients treated with GBT alone
regardless of geography or MAC species, and across a wide range of
amikacin MICs. Not surprisingly, we observed lower culture
conversion rates overall among patients with amikacin MIC > 64
μg/mL or macrolide MIC ≥ 32 μg/mL.”
Extension Study of Amikacin Liposome Inhalation Suspension
(ALIS) for Treatment-Refractory Lung Disease Caused by
Mycobacterium avium Complex (MAC): Interim Analysis
In a poster presentation on October 10, researchers reported
interim results from the ongoing open-label single-arm extension of
the Phase 3 CONVERT study (INS-312) evaluating the long-term safety
and tolerability of once-daily ARIKAYCE in patients who did not
achieve culture conversion by Month 6 in CONVERT. As of the July
2017 data cutoff for this analysis, results were consistent with
the safety and tolerability of ARIKAYCE plus GBT observed in the
CONVERT trial. Treatment-emergent adverse events were reported by
72.9% of patients who had previously received ARIKAYCE plus GBT in
CONVERT and by 93.2% of patients who had ARIKAYCE added to GBT in
INS-312. There were no new safety signals.
Additionally, 27.4% of patients (17/62) who initiated add-on
ARIKAYCE in the extension study achieved culture conversion, which
is consistent with the 29.0% rate of culture conversion achieved by
patients receiving ARIKAYCE plus GBT in the CONVERT study.
Continuation of ARIKAYCE was associated with culture conversion in
6.1% of patients (3/49) who had received ARIKAYCE plus GBT in
CONVERT but had not achieved culture conversion during that
study.
ARIKAYCE is administered once daily using the Lamira™ Nebulizer
System (PARI Pharma GmbH [PARI]).
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 needs. Current guideline-based treatment
involves the use of multi-drug regimens that are not specifically
approved for MAC lung disease. The course of treatment is often two
years or more and is inadequate in treating the disease in many
patients.
About ARIKAYCE® (amikacin liposome
inhalation suspension)
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. 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 it is taken up by lung macrophages where the
infection resides. This approach prolongs the release of amikacin
in the lungs while limiting systemic exposure. ARIKAYCE is
administered once daily using the Lamira™ Nebulizer System
manufactured by PARI Pharma GmbH.
About PARI Pharma and the Lamira™ Nebulizer
System
ARIKAYCE® (amikacin liposome inhalation suspension) 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) and INS-312
CONVERT is a randomized, open-label, global Phase 3 trial
designed to confirm the sputum culture conversion results seen in
Insmed's Phase 2 clinical trial of ARIKAYCE in patients with
refractory NTM lung disease caused by MAC. CONVERT is being
conducted in 18 countries at more than 125 sites. The primary
efficacy endpoint is the proportion of patients who achieved sputum
culture conversion at Month 6 in the ARIKAYCE plus GBT arm compared
to the GBT-only arm. Patients who achieved sputum culture
conversion by Month 6 are continuing in the CONVERT study for an
additional 12 months of treatment following the first monthly
negative sputum culture. Patients who did not culture convert may
have been eligible to enroll in our INS-312 study. INS-312 is a
single-arm open-label extension study for patients who completed
six months of treatment in the INS-212 study but did not
demonstrate culture conversion by Month 6. Under the study
protocol, non-converting patients in the ARIKAYCE plus GBT arm
of the INS-212 study will receive an additional 12 months of
ARIKAYCE plus GBT. Patients who crossed over from the GBT-only arm
of the INS-212 study will receive 12 months of treatment of
ARIKAYCE plus GBT.
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 ARIKAYCE® (amikacin
liposome inhalation suspension), which is approved in the United
States 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.
MAC lung disease is a rare and often chronic infection that can
cause irreversible lung damage and can be fatal. Insmed's
earlier-stage clinical pipeline includes INS1007, a novel oral
reversible inhibitor of dipeptidyl peptidase 1 with therapeutic
potential in non-cystic fibrosis bronchiectasis and other
inflammatory diseases, and INS1009, an inhaled nanoparticle
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.
IMPORTANT SAFETY INFORMATION
WARNING: RISK OF INCREASED
RESPIRATORY ADVERSE REACTIONSARIKAYCE 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.
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.
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 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.
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: risks that the remainder of the data from the treatment
and off-treatment phases of INS-212 will not be consistent with the
six-month results of the study; uncertainties in the research and
development of the Company’s existing product candidates, including
due to delays in data readouts, such as the full data from the
INS-212 study, patient enrollment and retention or failure of the
Company’s preclinical studies or clinical trials to satisfy
pre-established endpoints, including secondary endpoints in the
INS-212 study and endpoints in the INS-212 extension study (the
INS-312 study); risks that subsequent data from the INS-312 study
will not be consistent with the interim results; imposition of
significant post-approval regulatory requirements on our product
candidates, including a requirement for a post-approval
confirmatory clinical study, or failure to maintain or obtain full
regulatory approval for the Company’s product candidates, if
received, due to a failure to satisfy post-approval regulatory
requirements, such as the submission of sufficient data from a
confirmatory clinical study; safety and efficacy concerns related
to the Company’s product candidates; uncertainties in the rate and
degree of market acceptance of product candidates, if approved;
inability to create an effective direct sales and marketing
infrastructure or to partner with third parties that offer such an
infrastructure for distribution of the Company’s product
candidates, if approved; failure to obtain, or delays in obtaining,
regulatory approval from the U.S. Food and Drug Administration,
Japan’s Ministry of Health, Labour and Welfare, Japan’s
Pharmaceuticals and Medical Devices Agency, the European Medicines
Agency, and other regulatory authorities for the Company’s product
candidates or their delivery devices, including due to insufficient
clinical data, selection of endpoints that are not satisfactory to
regulators or complexity in the review process for combination
products; lack of experience in conducting and managing preclinical
development activities and clinical trials necessary for regulatory
approval, including the regulatory filing and review process;
inaccuracies in the Company’s estimates of the size of the
potential markets for the Company’s product candidates or
limitations by regulators on the proposed treatment population for
the Company’s product candidates; failure of third parties on which
the Company is dependent to conduct the Company’s clinical trials,
to manufacture sufficient quantities of the Company’s product
candidates for clinical or commercial needs, including the
Company’s raw materials suppliers, or to comply with the Company’s
agreements or laws and regulations that impact the Company’s
business; inaccurate estimates regarding the Company’s future
capital requirements, including those necessary to fund the
Company’s ongoing clinical development, regulatory and
commercialization efforts as well as milestone payments or
royalties owed to third parties; failure to develop, or to license
for development, additional product candidates, including a failure
to attract experienced third-party collaborators; uncertainties in
the timing, scope and rate of reimbursement for the Company’s
product candidates; changes in laws and regulations applicable to
the Company’s business and failure to comply with such laws and
regulations; inability to repay the Company’s existing indebtedness
or to obtain additional capital when needed on desirable terms or
at all; failure to obtain, protect and enforce the Company’s
patents and other intellectual property and costs associated with
litigation or other proceedings related to such matters;
restrictions imposed on the Company by license agreements that are
critical for the Company’s product development, including the
Company’s license agreements with PARI Pharma GmbH and AstraZeneca
AB, and failure to comply with the Company’s obligations under such
agreements; competitive developments affecting the Company’s
product candidates and potential exclusivity related thereto; the
cost and potential reputational damage resulting from litigation to
which the Company is or may become a party; loss of key personnel;
and lack of experience operating internationally.
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, 2017 and any subsequent Company filings with the Securities and
Exchange Commission.
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 Securities and
Exchange Commission, 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:
Blaine Davis Insmed Incorporated (908) 947-2841
blaine.davis@insmed.com
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