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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`Food and Drug Administration
`Silver Spring MD 20993
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`APPROVAL LETTER
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`NDA 20-845/S-009
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`INO Therapeutics, Inc.
`Attention: Mary Ellen Zamstein
`Senior Director, Regulatory Affairs
`6 State Route 173
`Clinton, NJ 08809
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`Dear Ms. Zamstein:
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`Please refer to your supplemental new drug application dated February 25, 2009, submitted under section
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`505(b) of the Federal Food, Drug, and Cosmetic Act for INOmax (nitric oxide) for Inhalation.
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`This supplemental new drug application provides for labeling revised as follows:
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`1. The label has been converted to the new PLR format.
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`2. The following text, which was originally under the DOSAGE AND ADMINISTRATION section,
`has been moved to the INDICATIONS AND USAGE section (this applies to both the FPI, and
`Highlights, where appropriate):
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`Utilize additional therapies to maximize oxygen delivery. In patients with collapsed alveoli,
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`additional therapies might include surfactant and high-frequency oscillatory ventilation.
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`The safety and effectiveness of inhaled nitric oxide have been established in a population receiving
`other therapies for hypoxic respiratory failure, including vasodilators, intravenous fluids, bicarbonate
`therapy, and mechanical ventilation. Different dose regimens for nitric oxide were used in the clinical
`studies [see Clinical Studies (14)].
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`Monitor for PaO2, methemoglobin, and inspired NO2 during INOmax administration.
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`3. The following new warning for use in patients with pre-existing left-ventricular dysfunction has been
`added to the appropriate sections of the label:
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`Highlights/RECENT MAJOR CHANGES:
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`Warnings and Precautions, Heart Failure (5.4)
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`8/2009
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`Highlights/WARNINGS AND PRECAUTIONS:
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`Heart Failure: In patients with pre-existing left ventricular dysfunction, inhaled nitric oxide may
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`increase pulmonary capillary wedge pressure leading to pulmonary edema (5.4).
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`Full Prescribing Information/WARNINGS AND PRECAUTIONS:
`5.4 Heart Failure
`Patients who had pre-existing left ventricular dysfunction treated with inhaled nitric oxide, even for
`short durations, experienced serious adverse events (e.g., pulmonary edema).
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` NDA 20-845/S-009
`Page 2
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`4. The first sentence of the OVERDOSAGE section has been changed from:
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`Overdosage with INOmax will be manifest by elevations in methemoglobin and NO2.
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`To:
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`Overdosage with INOmax will be manifest by elevations in methemoglobin and pulmonary toxicities
`associated with inspired NO2.
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`5. Under CLINICAL PHARMACOLOGY/Mechanism of Action, the following sentence has been
`added to the end of the first paragraph:
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`When inhaled, nitric oxide selectively dilates the pulmonary vasculature, and because of efficient
`scavenging by hemoglobin, has minimal effect on the systemic vasculature.
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`6. Under CLINICAL STUDIES, the title of the subsection on ARDS has been changed from:
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`Other Clinical Data: Adult Respiratory Distress Syndrome (ARDS)
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`To:
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`Ineffective in Adult Respiratory Distress Syndrome (ARDS)
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`7. The revision date has been updated.
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`We completed our review of this supplemental new drug application. It is approved, effective on the date
`of this letter, for use as recommended in the enclosed agreed-upon labeling text.
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`As soon as possible, but no later than 14 days from the date of this letter, please submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format as described at
`http://www.fda.gov/oc/datacouncil/spl.html that is identical to the enclosed labeling. Upon receipt, we
`will transmit that version to the National Library of Medicine for public dissemination. For administrative
`purposes, please designate this submission, “SPL for approved NDA 20-845/S-009.” Approval of this
`submission by FDA is not required before the labeling is used.
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`If you issue a letter communicating important information about this drug product (i.e., a “Dear Health
`Care Professional” letter), we request that you submit a copy of the letter to this NDA and a copy to the
`following address:
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`MedWatch
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`Food and Drug Administration
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`Suite 12B05
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`5600 Fishers Lane
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`Rockville, MD 20857
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`We remind you that you must comply with the requirements for an approved NDA set forth under
`21 CFR 314.80 and 314.81.
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` NDA 20-845/S-009
`Page 3
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`If you have any questions, please call Mr. Russell Fortney, Regulatory Project Manager, at (301) 796-
`1068.
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`Sincerely,
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`{See appended electronic signature page}
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`Norman Stockbridge, M.D., Ph.D.
`Director
`Division of Cardiovascular and Renal Products
`Office of Drug Evaluation I
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`Center for Drug Evaluation and Research
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`Enclosure: Agreed-upon labeling text
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`NORMAN L STOCKBRIDGE
`08/26/2009
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