Insmed Incorporated INSM today reported results from the Company's
phase 2 clinical trial of ARIKAYCE^TM, or liposomal amikacin for inhalation,
for the treatment of patients with treatment resistant nontuberculous
mycobacterial (NTM) lung infections. The randomized, double-blind,
placebo-controlled phase 2 clinical trial compared ARIKAYCE (590 mg delivered
once daily), added to standard of care treatment, versus standard of care
treatment plus placebo, in 90 adult patients with treatment resistant NTM lung
disease. 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 continue
to have persistently positive mycobacterial cultures.
The primary efficacy endpoint of the study was a semi-quantitative measurement
of the change in mycobacterial density on a seven-point scale from baseline
(day one) to the end of the randomized portion of the trial (day 84). ARIKAYCE
did not meet the pre-specified level for statistical significance although
there was a positive trend (p=0.148) in favor of ARIKAYCE. However, ARIKAYCE
did achieve statistical significance with regard to the clinically relevant
key secondary endpoint of culture conversion, with 11 out of 44 patients
treated with ARIKAYCE (added to standard of care treatment) demonstrating
negative cultures by day 84 of the study as compared to 3 out of 45 patients
treated with placebo (added to standard of care treatment) (p=0.01).
Patients receiving ARIKAYCE experienced a greater number of adverse events
than those receiving placebo. All adverse events experienced with ARIKAYCE
were consistent with those seen in similar patient populations receiving
inhaled antibiotics. The most common side effect was laryngeal irritation.
The Company plans to incorporate these results into discussions with the
regulatory agencies in the United States and Europe to determine next steps
for ARIKAYCE. The Company also intends to apply for Breakthrough Therapy
Designation for ARIKAYCE in the United States based upon the culture
conversion results. ARIKAYCE has already received Orphan Drug, Qualified
Infectious Disease Product (QIDP) and Fast Track designations from the U.S.
Food and Drug Administration (FDA) for the treatment of NTM lung infections
and recently received Orphan Drug Designation from the European Medicines
Agency (EMA).
“The results relating to the key secondary endpoint of culture conversion are
encouraging, and I believe demonstrate that ARIKAYCE has the potential to be
an option for treating even the most difficult treatment resistant patients
with NTM lung infections,” 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 a co-Principal Investigator on the study.
“We are encouraged by the achievement of culture conversion in this trial,
which we believe is the ultimate goal in the treatment of mycobacterial
infections,” said Dr. Renu Gupta, Executive Vice President, Development and
Chief Medical Officer of Insmed. “The design of this trial was such that the
patients who entered the trial and received drug were clearly resistant to
guideline therapy, making them the most treatment-challenged NTM patients.
Therefore the hurdle for showing any improvement with a therapy is extremely
high.”
“While ARIKAYCE did not achieve statistical significance on the primary
endpoint of bacterial density reduction, we are very pleased by the greater
number of culture conversions among patients receiving ARIKAYCE,” stated Will
Lewis, President and Chief Executive Officer of Insmed. “We now look forward
to the regulatory discussions in the US and Europe that will guide our path
forward.”
“We extend our gratitude to the investigators and their patients who
participated in this study,” concluded Mr. Lewis.
Primary Endpoint
The objective of the primary endpoint was to show a reduction in the density
of bacteria of at least one step along a seven point scale as a means of
identifying whether a trend suggestive of ultimate culture conversion could be
established. The number of patients showing at least a one-step reduction in
the treatment arm versus those in the placebo arm was not statistically
significant (p=0.148). The design of the study's primary endpoint was not
culture conversion because it was assumed that culture conversion would not be
achievable in 84 days treatment, particularly given the severe,
treatment-resistant patient population that was the subject of this study.
Secondary Endpoints
ARIKAYCE achieved statistical significance with regard to the secondary
outcome of culture conversion, with 11 out of 44 patients treated with
ARIKAYCE demonstrating negative cultures by day 84 of the study as compared to
3 out of 45 patients treated with placebo arm (standard of care therapy only)
(p=0.01). Data analyses for additional secondary, tertiary and exploratory
endpoints are ongoing and will be discussed at a presentation at the American
Thoracic Society meeting in May.
Safety
Patients receiving ARIKAYCE experienced adverse events consistent with those
seen in similar patient populations receiving inhaled antibiotics. Overall,
mild to moderate throat irritation was more common in the ARIKAYCE arm
compared to the placebo arm. One Suspected Unexpected Serious Adverse Reaction
(SUSAR) was observed in the ARIKAYCE arm, but there was no difference in
severe serious adverse reactions or hemoptysis between the two arms. Instances
of hearing loss or tinnitus, a side effect more commonly associated with
intravenous dosing of amikacin, were evenly balanced between the ARIKAYCE and
placebo arms. The study population was chronically ill with a mean age of 61.
Clinical Trial Design
Mycobacterial density is a measurement currently used in clinical practice to
assess the progress or decline of those patients with recalcitrant NTM.
Following the randomized portion of the study, all eligible patients had the
option to receive ARIKAYCE once daily for an additional 84 days in an
open-label design.
Patients in the trial were stratified for either Mycobacterium avium complex
(MAC) infections or Mycobacterium abscessus infections. These pathogens
collectively account for approximately 85% of all patients with NTM lung
disease in the U.S. Stratification was also performed based on patients with
cystic fibrosis versus those who do not have cystic fibrosis.
Conference Call and Webcast
Insmed management will host an investment community conference call today at
8:00 a.m. Eastern time, featuring several clinical trial investigators who are
experts in NTM. Shareholders and other interested parties may participate in
the call by dialing 888-803-5993 (domestic) or 706-634-5454 (international)
and referencing conference ID number 19390649. The call will be webcast live
and archived at http://investor.insmed.com/events.cfm.
A replay of the conference call will be accessible two hours after its
completion through April 1, 2014 by dialing 855-859-2056 (domestic) or
404-537-3406 (international) and referencing conference ID number 19390649.
The call will also be archived for 90 days on the Company's website at
www.insmed.com.
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