Data in American Journal of Respiratory and
Critical Care Medicine demonstrate ARIKAYCE’s potential to
achieve early and sustained negative sputum cultures
Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical
company focused on the unmet needs of patients with rare diseases,
today announced the online publication of data from its phase 2
study of ARIKAYCE™ (liposomal amikacin for inhalation or LAI) in
the American Journal of Respiratory and Critical Care Medicine.
ARIKAYCE is a novel formulation of amikacin administered once-daily
using an optimized eFlow® Electronic Nebulizer (PARI Pharma GmbH).
ARIKAYCE is being studied in treatment-refractory nontuberculous
mycobacterial (NTM) lung disease.
The phase 2 study evaluated ARIKAYCE in patients with
nontuberculous mycobacterial lung infections who had been unable to
achieve culture conversion to negative despite receiving a
multi-drug guideline-based regimen for six or more months. Although
the primary endpoint was not reached, data from the study suggest
that the addition of ARIKAYCE to the guideline-based multi-drug
regimen can achieve early and sustained negative sputum cultures.
In addition, culture conversion resulting from ARIKAYCE plus
multi-drug treatment was associated with improvements in the
six-minute walk test. ARIKAYCE is currently being evaluated in a
global phase 3 randomized open-label clinical study designed to
evaluate the culture conversion results observed in the phase 2
clinical study. The phase 3 study, which is known as the CONVERT
study, is enrolling adult non-cystic fibrosis patients with an NTM
lung infection caused by Mycobacterium avium complex
(MAC).
“Pulmonary nontuberculous mycobacterial disease is a chronic,
progressive infection associated with irreversible lung damage and
mortality,” said Eugene Sullivan, MD, chief medical officer of
Insmed. “Current treatment options are not approved for pulmonary
NTM and are limited to lengthy multi-drug regimens that are
associated with intolerance, treatment failures, and problematic
multi-drug interactions. The novel drug formulation of liposomal
amikacin for inhalation delivers high levels of a potent
aminoglycoside directly to the lung macrophages where the infection
resides. There is an important unmet need among patients with
refractory NTM lung disease and data from this phase 2 study
suggest that liposomal amikacin could be a treatment
option.”
Insmed’s clinical development program in refractory NTM lung
disease represents the largest and most comprehensive program
conducted to date. Insmed has received multiple designations for
ARIKAYCE from the U.S. Food and Drug Administration (FDA) for the
treatment of NTM, including: orphan, breakthrough therapy,
Qualified Infectious Disease Product (QIDP), and Fast Track status.
Products in development under QIDP status gain certain incentives
if they are approved by the FDA, which include a five-year
extension of data exclusivity provisions and priority review of its
NDA. Fast Track status is intended to facilitate development and
expedite review of drugs to treat serious and life-threatening
conditions.
Study Design
The phase 2 study was a randomized, double-blind,
placebo-controlled study that evaluated the efficacy and safety of
ARIKAYCE in adults with NTM lung disease due to MAC or
Mycobacterium abscessus (M. abscessus) that was refractory to
guideline-based therapy. Eligibility for the study required
patients to have been on the American Thoracic Society/Infectious
Disease Society of America (ATS/IDSA) guideline therapy for at
least six months prior to screening and to have had persistently
positive mycobacterial cultures. The study included an 84-day
double-blind phase in which subjects were randomized 1:1 either to
ARIKAYCE once-daily plus a multi-drug regimen or to placebo
once-daily plus a multi-drug regimen. After completing the 84-day
double-blind phase, subjects had the option of continuing in an
84-day open-label phase during which all subjects received ARIKAYCE
plus a multi-drug regimen. The study also included 28-day and
12-month off-ARIKAYCE follow-up assessments.
Study Results
Eighty-nine subjects were randomized and dosed in the study. Of
the 80 subjects who completed the 84-day double-blind phase, 78
subjects entered the open-label phase during which all patients
received ARIKAYCE plus a multi-drug regimen for 84 days.
Seventy-six (76) percent (59/78) of subjects who entered the
open-label phase of the study completed the open-label study.
The primary efficacy endpoint of the study was the change from
baseline (day 1) to the end of the double-blind phase of the trial
(day 84) in a semi-quantitative measurement of mycobacterial
density on a seven-point scale. The primary endpoint did not reach
statistical significance; however, a positive numerical trend in
favor of ARIKAYCE was observed (p=0.072). The p-value for the key
secondary endpoint of culture conversion to negative at Day 84 was
0.003, in favor of ARIKAYCE. A shorter time to first negative
sputum culture was also observed with ARIKAYCE relative to placebo
during the double-blind phase (p=0.013).
The microbiologic outcomes from the study were also explored
post hoc using a more stringent definition of culture conversion,
which is defined as at least three consecutive monthly sputum
samples that test negative for NTM. This definition of culture
conversion is in the guidelines and used in clinical practice.
Twenty-three subjects achieved at least three consecutive
negative monthly sputum samples by the 28-day follow-up assessment,
of which four started to convert at baseline prior to
administration of study drug. For the 19 patients who achieved
culture conversion, 17 achieved culture conversion after receiving
ARIKAYCE, 10 who were randomized to ARIKAYCE in the double-blind
phase and seven after entering the open-label phase. Two patients
achieved culture conversion while receiving placebo in the
double-blind phase.
The majority of patients who achieved culture conversion (three
consecutive negative monthly sputum samples) during the
double-blind phase continued to have negative cultures through the
open-label and follow-up phases.
At the end of the double-blind phase, the ARIKAYCE group
improved from baseline in mean distance walked in the six-minute
walk test. At the end of the open-label phase, patients in
the ARIKAYCE group continued to improve in the mean distance walked
in the six-minute walk test while the patients who previously
received placebo in the double-blind phase and subsequently
received ARIKAYCE in the open-label phase demonstrated a reduced
rate of decline from baseline.
The majority (90 percent) of patients in both
treatment groups experienced at least one treatment-emergent
adverse event with most events either mild or moderate in severity.
During the double-blind phase a greater percentage of patients
treated with ARIKAYCE experienced dysphonia, bronchiectasis
exacerbation, cough, oropharyngeal pain, fatigue, chest discomfort,
wheezing, and infective pulmonary exacerbation of cystic fibrosis.
No clinically relevant changes were detected in laboratory values
and vital signs.
About Nontuberculous Mycobacteria Lung
Disease
NTM is a rare and serious disorder associated with
increased morbidity and mortality. There is an increasing rate of
lung disease caused by NTM and this is an emerging public health
concern worldwide. Patients with NTM lung disease may experience a
multitude of symptoms such as fever, weight loss, cough, lack of
appetite, night sweats, blood in the sputum, and fatigue. Patients
with NTM lung disease frequently require lengthy hospital stays to
manage their condition. There are no products specifically
indicated for the treatment of NTM lung disease in the US, Europe
and Canada. Current guideline-based approaches involve multi-drug
regimens that may cause severe side effects and treatment can be as
long as two years or more.
The prevalence of human disease attributable to NTM
has increased over the past two decades. In a decade long study
(1997 to 2007), researchers found that the prevalence of NTM in the
US is increasing at approximately 8% per year and that NTM patients
on Medicare over the age of 65 are 40% more likely to die over the
period of the study than those who did not have the disease. A 2015
publication from co-authors from several US government departments
projected 181,037 national annual cases in 2014 costing the US
healthcare system approximately $1.7 billion.
For more information about NTM lung disease, visit
NTMfacts.com.
About ARIKAYCE
ARIKAYCE, or liposomal amikacin for inhalation, is
a novel, once daily formulation of amikacin that is in late-stage
clinical development for patients with NTM lung disease. Amikacin
solution for parenteral administration is an established drug that
is effective against a variety of NTM; however, its use is limited
by the need to administer it intravenously and by toxicity to
hearing, balance, and kidney function. Insmed’s advanced pulmonary
liposome technology uses charge neutral liposomes to deliver
amikacin directly to the lung where it is taken up by the lung
macrophages where the NTM infection resides. This prolongs the
release of amikacin in the lungs while minimizing systemic exposure
thereby offering the potential for decreased systemic toxicities.
ARIKAYCE’s ability to deliver high levels of amikacin directly to
the lung distinguishes it from intravenous amikacin. ARIKAYCE is
administered once daily using an optimized, investigational eFlow®
Nebulizer System manufactured by PARI Pharma GmbH, a novel, highly
efficient and portable aerosol delivery system.
About PARI Pharma and the eFlow® Electronic
Nebulizer
Arikayce is delivered by a novel, inhalation
device, the eFlow® Electronic Nebulizer, developed by PARI Pharma
GmbH. eFlow 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 Pharma is dedicated to advancing inhalation
therapies by developing innovative platforms and new pharmaceutical
formulations that work together to improve patient care.
About Insmed
Insmed Incorporated is a global biopharmaceutical
company focused on the unmet needs of patients with rare diseases.
The company is advancing a global phase 3 clinical study of
ARIKAYCE (liposomal amikacin for inhalation) in nontuberculous
mycobacteria (NTM) lung disease, a rare and often chronic infection
that is capable of causing irreversible lung damage and can be
fatal. There are currently no products indicated for the treatment
of NTM lung disease in the United States or European Union (EU).
Insmed’s earlier-stage clinical pipeline includes INS1007, a novel
oral inhibitor of dipeptidyl peptidase I with therapeutic potential
in non-cystic fibrosis bronchiectasis, and INS1009, a nebulized
prodrug formulation of treprostinil that may offer a differentiated
product profile for rare pulmonary disorders such as pulmonary
arterial hypertension (PAH), idiopathic pulmonary fibrosis (IPF),
sarcoidosis, and severe refractory asthma. To complement its
internal research, Insmed actively seeks in-licensing opportunities
for a broad range of rare diseases. For more information,
visit www.insmed.com.
“Insmed” and “ARIKAYCE” are the company's
trademarks. All other trademarks, trade names or service marks
appearing in this press release are the property of their
respective owners.
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are statements that are not historical facts and involve a number
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uncertainties and other factors, which may cause actual results,
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differ materially from the results, performance, achievements or
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forward-looking statements. Such factors include, among others, the
factors discussed in Item 1A “Risk Factors” in the company’s Annual
Report on Form 10-K for the year ended December 31, 2015 and
subsequent quarterly reports on Form 10-Q, and the following: the
ability to complete development of, receive, and maintain
regulatory approval for, and successfully commercialize ARIKAYCE,
INS1007 (formerly known as AZD7986), and INS1009; the number of
patients enrolled and the timing of patient enrollment in the
company’s global phase 3 clinical study of ARIKAYCE; estimates of
expenses and future revenues and profitability; status, timing, and
the results of preclinical studies and clinical trials and
preclinical and clinical data described herein; the sufficiency of
preclinical and clinical data in obtaining regulatory approval for
the company’s product candidates; the timing of responses to
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licensing of product candidates; ability to attract third parties
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limitation, the class action lawsuit recently filed against the
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The company cautions readers not to place undue
reliance on any such forward-looking statements, which speak only
as of the date they are made. Insmed disclaims any obligation,
except as specifically required by law and the rules of the
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Insmed Incorporated:
Susan Mesco
Head of Investor Relations
908-947-4326
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