Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical
company focused on the unmet needs of patients with rare diseases,
today announced top-line data from its Phase 3 CONVERT study.
Top-Line Efficacy Data
The global CONVERT study met its primary endpoint of culture
conversion by Month 6 with statistical and clinical
significance. The study demonstrated that the addition of
ALIS to guideline-based therapy (GBT) eliminated evidence of NTM
lung disease caused by MAC in sputum by Month 6 in 29% of patients,
compared to 9% of patients on GBT alone (p <0.0001). The trial
was powered to detect a treatment effect of 15% between the two
treatment groups. The CONVERT study enrolled 336 adult
patients with NTM lung disease caused by MAC who were refractory to
at least six months of GBT. Patients were randomized 2:1 to
receive ALIS plus GBT versus GBT alone. The primary endpoint
was the proportion of patients achieving culture conversion by
Month 6.
Insmed plans to pursue accelerated approval of ALIS under
subpart H based on the data from the CONVERT study, which will be
reviewed by the Division of Anti-Infective Products. FDA
previously granted this product breakthrough therapy designation
and fast track status and designated ALIS as a qualified infectious
disease product (QIDP) under the Generating Antibiotic Incentives
Now (GAIN) Act.
“We consider these compelling top-line data to be a remarkable
accomplishment in a rare disease state with no currently approved
therapies,” said Will Lewis, President and Chief Executive Officer
of Insmed. “We are particularly encouraged by the consistency of
these data when compared with our Phase 2 study results, and look
forward to additional data as the CONVERT study continues over the
next two years. We want to thank all the patients who
participated in this trial around the world as well as the
physicians who supported them. Treatment of this serious and
potentially debilitating disease is an unmet medical need, and we
expect these important data will enable us to submit for
accelerated approval.”
The Company also reported top-line data for several secondary
endpoints as of the 6-month timepoint. Top-line data for the
6-minute walk test indicates no statistically significant
difference between patients in the two arms. However, an
analysis of these data (per a pre-specified endpoint) shows that
patients who achieved culture conversion in either arm demonstrated
an improvement in 6-minute walk distance when compared to patients
who did not culture convert (p=0.0108). Top-line data for the
secondary endpoint of time to conversion demonstrated that patients
on GBT took approximately 30% longer to convert when compared to
patients on ALIS plus GBT (p<0.0001). The Company is
continuing its analysis of the impact of conversion on a variety of
other clinical measures.
“I am extremely pleased with and impressed by the culture
conversion results that ALIS demonstrated in treatment-refractory
patients with NTM lung disease caused by MAC. The
eradication of MAC is the first and most important goal for
treatment of 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 Sciences Center and
Principal Investigator in the CONVERT study. “I am not only
encouraged by the higher conversion rate, but also by the faster
time to conversion and safety profile of patients in the ALIS arm
of the study. Although it is not a parameter routinely
used in clinical practice, I also find it encouraging that
patients who achieved culture conversion showed improvement in
6-minute walk distance, a quality of life parameter, as was seen in
a prior ALIS study.”
"Today marks an important advance in our quest to bring a safe
and effective treatment to patients who suffer from NTM lung
disease caused by MAC. This represents the first ever global
Phase 3 controlled study in patients with NTM, a rare, progressive
and destructive infection that is associated with irreversible lung
damage and increased rates of mortality," said Paul Streck, M.D.,
Chief Medical Officer of Insmed. "The current guideline-based
therapy to which we were compared in this study is not approved for
the treatment of this disease, but is generally regarded as the
best available option for these patients. Our drug candidate,
ALIS, delivers high levels of an aminoglycoside directly to the
lung macrophages and pulmonary tissue where the infection resides,
and we believe this accounts for the significant impact on
conversion that the drug demonstrated in these trial results.”
Safety and Tolerability
In the study, serious treatment emergent adverse events were
similar between treatment arms. There were no distinctions
between treatment arms due to hearing loss or renal impairment,
side effects commonly associated with intravenous use of
amikacin. The overall dropout rate was 16.1%, with an 8.9%
dropout rate in the GBT arm and a 19.6% rate in the ALIS plus GBT
arm. Overall the rate of reported adverse events in the ALIS
plus GBT arm was higher and these events were predominately mild or
moderate in nature and generally declined after the second month of
treatment. These findings are consistent with the Phase 2
study results and demonstrate adverse events similar to those seen
in other clinical studies of inhaled antibiotics.
Patients Reporting Serious Treatment Emergent Adverse
Events >3% in Either Arm |
|
2:1 Randomization |
|
|
ALIS + GBT (n=223) |
|
GBT (n=112) |
Patients Reporting At least One Serious Treatment Emergent Adverse
Event |
|
20.2% (45) |
|
17.9% (20) |
|
|
|
|
|
System Organ Class |
Preferred Term |
|
|
|
Respiratory, Thoracic, Mediastinal Disorders |
|
11.7% (26) |
|
9.8% (11) |
|
Hemoptysis |
2.7% (6) |
|
4.5% (5) |
|
COPD (exacerbation) |
3.1% (7) |
|
0.9% (1) |
Infections and Infestations |
|
9.0% (20) |
|
5.4% (6) |
|
Pneumonia |
3.6% (8) |
|
1.8% (2) |
Cardiac Disorders |
|
0.4% (1) |
|
4.5% (5) |
Patient Deaths |
|
2.7% (6) |
|
4.5% (5) |
Conference Call
Insmed will host a conference call beginning today at 8:30 am
Eastern Time. Shareholders and other interested parties may
participate in the conference call by dialing (844) 707-0669
(domestic) or (703) 639-1223 (international) and referencing
conference ID number 79817122. The call will also be webcast
live on the company’s website.
To access the live webcast, or the subsequent archived
recording, visit the Investors section of the Insmed website at
www.insmed.com. The webcast will be available for replay on
Insmed’s website for two weeks following the call.
About NTM Lung Disease
NTM is a rare and serious disorder associated with increased
rates of morbidity and mortality. There is an increasing prevalence
of lung disease caused by NTM, and we believe it 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. We are not
aware of any approved inhaled therapies specifically indicated for
refractory NTM lung disease caused by MAC in North America, Japan
or Europe. Current guideline-based approaches involve use of
multi-drug regimens not approved for the treatment of NTM lung
disease, 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
was increasing at approximately 8% per year and that NTM patients
on Medicare over the age of 65 were 40% more likely to die over the
period of the study than those who did not have the disease. In the
US, we estimate there will be between 75,000 and 105,000 patients
with diagnosed NTM lung disease in 2018, of which we expect 40,000
to 50,000 will be treated for NTM lung disease caused by MAC.
We expect that between 10,000 and 15,000 of these patients will be
refractory to treatment. In Japan, we estimate there will be
between 125,000 and 145,000 patients with diagnosed NTM lung
disease in 2018, with approximately 60,000 to 70,000 of those
patients being treated for NTM lung disease caused by MAC and
15,000 to 18,000 of these treated patients being refractory to
treatment. We also estimate there will be approximately 14,000
patients with diagnosed NTM lung disease in the EU5 (comprised of
France, Germany, Italy, Spain and the United Kingdom) in 2018, of
which we estimate approximately 4,400 will be treated for NTM lung
disease caused by MAC and approximately 1,400 of these treated
patients will be refractory to treatment.
About ALIS
ALIS is a novel, inhaled, once daily formulation of amikacin
that is in late-stage clinical development for adult patients with
treatment-refractory NTM lung disease caused by MAC. Amikacin
solution for parenteral administration is an established drug that
has activity 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.
ALIS’s ability to deliver high levels of amikacin directly to the
lung distinguishes it from intravenous amikacin. ALIS is
administered once daily using an optimized, investigational eFlow®
Nebulizer System manufactured by PARI Pharma GmbH (PARI), a
portable aerosol delivery system.
About CONVERT
CONVERT is a randomized, open-label, global Phase 3 trial
designed to confirm the culture conversion results seen in Insmed’s
Phase 2 clinical trial of ALIS 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 achieve culture conversion at Month 6 in
the ALIS plus GBT arm compared to the GBT-only arm. Patients
who achieve culture conversion by Month 6 will continue in the
CONVERT study for an additional 12 months of treatment following
the first monthly negative sputum culture. Patients who do not
culture convert have the option of enrolling in our INS-312 study.
INS-312 is a single-arm open-label study where patients will
receive ALIS plus GBT for 12 months.
About Insmed
Insmed Incorporated is a global biopharmaceutical company
focused on the unmet needs of patients with rare diseases. Our lead
product candidate is ALIS for adult patients with treatment
refractory NTM lung disease caused by MAC, which is a rare and
often chronic infection that is capable of causing irreversible
lung damage and can be fatal. We are not aware of any approved
inhaled therapies specifically indicated for refractory NTM lung
disease caused by MAC in North America, Japan or Europe.
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
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.
Forward-looking Statements
This press release contains forward looking statements.
"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
factors include, among others: risks that the full six-month data
from the CONVERT study or subsequent data from the remainder of the
study’s treatment and off-treatment phases will not be consistent
with the top-line six-month results of the study; uncertainties in
the research and development of our existing product candidates,
including due to delays in data readouts, such as the full data
from the CONVERT study, patient enrollment and retention or failure
of our preclinical studies or clinical trials to satisfy
pre-established endpoints, including secondary endpoints in the
CONVERT study and endpoints in the INS-312 study; lack of safety
and efficacy of our product candidates; failure to develop, or to
license for development, additional product candidates, including a
failure to attract experienced third-party collaborators; failure
to obtain, or delays in obtaining, regulatory approval from the
United States Food and Drug Administration, Japan’s Ministry of
Health, Labour and Welfare, the European Medicines Agency, and
other regulatory authorities for our product candidates or their
delivery devices, including due to insufficient clinical data or
selection of endpoints that are not satisfactory to regulators,
complexity in the review process for combination products or
inadequate or delayed data from a human factors study required for
U.S. regulatory approval; lack of experience in conducting and
managing preclinical development activities and clinical trials
necessary for regulatory approval, including the regulatory filing
and review process; failure of third parties on which we are
dependent to conduct our clinical trials, to manufacture sufficient
quantities of our product candidates for clinical or commercial
needs, or to comply with our agreements or laws and regulations
that impact our business; failure to comply with license agreements
that are critical for our product development, including our
license agreements with PARI Pharma GmbH and AstraZeneca AB;
inaccuracies in our estimate of the size of the potential markets
for our product candidates; failure to maintain regulatory approval
for our product candidates, if received, due to a failure to
satisfy post-approval regulatory requirements, such as the
submission of sufficient data from confirmatory clinical trials;
uncertainties in the rate and degree of market acceptance of
product candidates, if approved; uncertainties in the timing, scope
and rate of reimbursement for our product candidates; competitive
developments affecting our product candidates; inaccurate estimates
regarding our future capital requirements, including those
necessary to fund our ongoing clinical development, regulatory and
commercialization efforts as well as milestone payments or
royalties owed to third parties; inability to repay our existing
indebtedness or to obtain additional financing when needed; failure
to obtain, protect and enforce our patents and other intellectual
property; inability to create an effective direct sales and
marketing infrastructure or to partner with third parties that
offer such an infrastructure for distribution of our product
candidates, if approved; the cost and potential reputational damage
resulting from litigation to which we are a party, including,
without limitation, the class action lawsuit pending against us;
failure to comply with the laws and regulations that impact our
business; loss of key personnel; and changes in laws and
regulations applicable to our business, including those related to
pricing and reimbursement of our product
candidates.
For additional information about the risks and uncertainties
that may affect our 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, 2016.
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.
Investor Contact:
Blaine Davis
Vice President, Head of Investor Relations
Insmed Incorporated
(908) 947-2841
blaine.davis@insmed.com
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