U.S. Food and Drug Administration Approves Kaleo's EVZIO™ for the Emergency Treatment of Opioid Overdose

RICHMOND, Va., April 3, 2014 /PRNewswire/ -- Kaleo (formerly Intelliject) today announced that the U.S. Food and Drug Administration (FDA) has approved EVZIO™ (naloxone hydrochloride injection) for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression. EVZIO is the first and only naloxone auto-injector intended to be available for immediate administration by family members or caregivers for suspected opioid overdose in settings where opioids may be present.¹

Opioids are part of a class of pain medications that work by binding to receptors in the brain that affect the body's perception of pain, and can cause fatal overdose when the amount of drug in the body is too high.² Opioids are used to treat pain associated with a variety of acute and chronic medical conditions. According to the Institute of Medicine, chronic pain affects about 100 million American adults – more than the total affected by heart disease, cancer and diabetes combined.³ More than 16,000 Americans die each year from prescription opioid overdose, and accidental drug poisoning has surpassed automobile collisions as the leading cause of accidental death in the U.S., driven largely by prescription opioids.^4,5

Naloxone, the active ingredient in EVZIO, has been used for more than 40 years for reversal of respiratory depression due to opioid overdose, but has been primarily used by emergency medical services, other medical professionals and in limited naloxone distribution programs.⁶ EVZIO will be available to patients and their family members or caregivers via a healthcare professional's prescription. EVZIO should be administered as quickly as possible when an opioid overdose is suspected because prolonged respiratory depression may result in damage to the central nervous system or death. Because people experiencing an opioid overdose generally lose consciousness, in most cases, family members or caregivers will likely be the ones who administer EVZIO. EVZIO uses voice and visual cues to assist in guiding a user through the injection process.¹

"Kaleo was founded on the idea that patients are true experts on how their conditions impact their lives, and EVZIO was developed with patient and caregiver input throughout to make sure it would be easy to use in stressful opioid emergencies with limited training," said Eric Edwards, MD, PhD, Chief Medical Officer of kaleo. "Immediate availability of EVZIO for family members and caregivers to administer during a suspected opioid overdose has the potential to save many lives."

"All patients taking an opioid pain medication accept some risk of potential overdose. No medication is side effect free, and potent pain relieving opioids have a narrow window of effectiveness, with some very serious possible side effects including potentially life-threatening respiratory depression," said Allen Burton, MD⁷, anesthesiologist and pain specialist at Houston Pain Centers and former chairman of the department of pain medicine at the University of Texas MD Anderson Cancer Center. "Until now, most people had to rely on emergency medical care to get access to an opioid reversal agent. Having naloxone available for use by caregivers as soon as signs of overdose are observed means an earlier intervention and better chance of survival."

The new drug application (NDA) for EVZIO was granted Fast Track status and received a priority review by the FDA, which are regulatory pathways to accelerate the review and approval of products that fill an unmet medical need. EVZIO is expected to be available this summer through all major pharmacies and via mail order with a healthcare professional's prescription. An assistance program will be available to help patients gain access to EVZIO.

"The FDA approval of EVZIO furthers our mission to make lifesaving products that put patients first," said Spencer Williamson, CEO of kaleo. "We are thankful to the patients and caregivers whose input guided the development process and resulted in an intuitive and important product we're proud to bring to market."

For more information on EVZIO, visit www.EVZIO.com.

Conference Call for Media
Kaleo will host a briefing for members of the media on Thursday, April 3, 2014, at 12 p.m. ET. Media can call 1-888-771-4371, confirmation number 37036155. The panel of speakers will include:

• Spencer Williamson, CEO of kaleo
• Eric Edwards, MD, PhD, Chief Medical Officer of kaleo
• Allen Burton, MD, anesthesiologist and pain specialist
• Knox H. Todd, MD, MPH, FACEP, emergency physician

About Opioid Overdose
Opioid overdose can cause a person's breathing to severely slow down and even stop. Opioid medications have a relatively narrow therapeutic window, meaning that even small changes – such as a single extra dose or the addition of a small amount of alcohol – can cause a potentially fatal overdose.⁸

Some risk factors for overdose include: history of substance abuse or dependence, taking high doses of opioids,⁶ no previous history of taking opioids,⁹ a recent dosage increase, extended-release or long-acting opioids,¹⁰ taking certain antidepressants like monoamine oxidase inhibitors (MAOIs) or certain drugs for anxiety, and a history of respiratory conditions such as asthma, COPD and sleep apnea.⁶ In addition, children living with someone consuming prescription opioids have been shown to be at increased risk.¹¹

Signs and symptoms of opioid overdose include very slow or absent breathing, loss of consciousness, extremely small pupils, and slow heartbeat.²

About EVZIO
EVZIO is a pre-filled, single-use auto-injector that works by temporarily blocking the effect of an opioid, potentially reversing the life-threatening respiratory depression and allowing the recipient to breathe more regularly. Once the effects of EVZIO wear off, the overdose symptoms may reappear and additional naloxone may be required. There is no potential for abuse or dependence with naloxone.¹

Each EVZIO delivers 0.4 mg naloxone hydrochloride injection (0.4 mL).

Indication

EVZIO is an opioid antagonist indicated for the emergency treatment of known or suspected opioid overdose, as manifested by respiratory and/or central nervous system depression.

EVZIO is intended for immediate administration as emergency therapy in settings where opioids may be present.

EVZIO is not a substitute for emergency medical care.

Important Safety Information

The following is important safety information associated with dosing and administration of EVZIO:

• EVZIO is for intramuscular or subcutaneous use only.
• Administer EVZIO to adult or pediatric patients into the anterolateral aspect of the thigh, through clothing if necessary.
• In pediatric patients under the age of one, the caregiver should pinch the thigh muscle while administering EVZIO.
• Seek emergency medical care immediately after use.
• The duration of action of most opioids is likely to exceed that of EVZIO resulting in a return of respiratory and/or central nervous system depression. Keep the patient under continued surveillance and repeated doses of EVZIO should be administered every 2 to 3 minutes, as necessary, while awaiting emergency medical assistance.
• If the electronic voice instruction system does not operate properly, EVZIO will still deliver the intended dose of naloxone hydrochloride when used according to the printed instructions on the flat surface of its label.

The following precautions should be taken when administering EVZIO:

• Consider other supportive and/or resuscitative measures while awaiting emergency medical assistance.
• Reversal of respiratory depression by partial agonists or mixed agonists/antagonists such as buprenorphine and pentazocine, may be incomplete or require higher doses of naloxone.
• Use in patients who are opioid dependent may precipitate acute abstinence syndrome.
• In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated.
• Patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects should be monitored in an appropriate healthcare setting.
• EVZIO should be used with caution in patients known to be hypersensitive to naloxone hydrochloride.

Opioid Withdrawal:
Abrupt reversal of opioid effects in persons who were physically dependent on opioids has precipitated signs and symptoms of opioid withdrawal including: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia.  In the neonate, opioid withdrawal signs and symptoms also included: convulsions, excessive crying, hyperactive reflexes.

Use in Post-Operative Settings:
The following adverse reactions have been identified during use of naloxone hydrochloride in the post-operative setting: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone hydrochloride in post-operative patients have resulted in significant reversal of analgesia and has caused agitation.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.  Please click here for full Prescribing Information.

About kaleo
Kaleo (formerly Intelliject) is a pharmaceutical company dedicated to putting a new generation of life-saving personal medical products in patients' hands. The company's first product, Auvi-Q™ (www.Auvi-Q.com) (Allerject™ in Canada), was licensed to Sanofi US which launched the product in early 2013. Our mission is to provide demonstrably superior medical products that empower patients and caregivers to confidently take control in potentially life-threatening situations. We believe patients and caregivers are the experts on how their medical condition impacts their lives, and are an integral part of our product development process. Each kaleo product combines an established drug with an innovative delivery platform with the goal of achieving superiority and cost effectiveness. Kaleo is a privately held company headquartered in Richmond, Virginia. For more information, visit www.kaleopharma.com.

©2014 kaleo, Inc. All rights reserved. PP-EVZ-US-0016 April 2014

SOURCE Kaleo