Apr 3 2014, 3:20pm CDT | by Forbes
The privately-held, Richmond, Virginia-based kaléo Pharma (formerly Intelliject) today received FDA approval for Evzio®, an automatic injector of the opioid overdose antidote, naloxone, specifically tested and intended for use by caregivers, family members, or coworkers.
The injection device approval came only four months after submission of their New Drug Application which was reviewed under FDA’s expedited, fast-track priority review, “a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need.”
In fact, approval of Evzio comes more than two-and-a-half months ahead of the agency’s planned June 20th completion date for review of the naloxone autoinjector.
The high-profile, opioid-related deaths of celebrities such as Heath Ledger, Cory Monteith, and Philip Seymour Hoffman have raised public consciousness of the dangers of opioid overdose. In most recent year for which data are available (2010), 16,651 people died of opioid overdoses .
That’s one opioid-related death every half hour, and that’s just in the U.S.
What is naloxone and what does it do?
Naloxone, available since 1971 as Narcan® for injection, is a potentially lifesaving drug in the event of accidental or intentional overdose with illicit opioids such as heroin or prescription opioids like oxycodone, hydrocodone, morphine, or fentanyl, among others.
When injected during the one-to-three hour time window where a patient or recreational drug user might be on the way to an overdose death, naloxone can reverse the binding of the other drug at the opioid receptors in the brain that control breathing. This intervention buys time for the person to be transported to a hospital for subsequent care.
In individuals with a history of hospitalization or rehab from opioid use, naloxone injection kits or nasal mist formulations have been distributed in some communities to family members or other caregivers. The Harm Reduction Coalition and the Lazarus Project are among such community groups.
But up to 60% of opioid overdoses occur in patients using their medicines as prescribed by their physicians. Some reasons are that opioid effects are intensified with anti-anxiety drugs, alcohol, and some antibiotics. In addition, patients with existing pulmonary problems such as asthma, sleep apnea of chronic obstructive pulmonary disease (COPD) are hypersensitive to the respiratory depressant effects of opioid pain relievers. Some children with a particular drug metabolism polymorphism are also hypersensitive to the opioid pain reliever, codeine.
So if naloxone has been on the market for over four decades, what makes kaléo’s naloxone autoinjector innovation so special?
Most importantly, the product overcomes a major hurdle that has prevented some states, such as Maine, from encouraging physician prescription of naloxone for use outside healthcare settings. Until recently, naloxone has only been intended for use by intravenous injection in emergency setting with paramedics or in hospital emergency rooms. The nasal spray of injectable naloxone is not an FDA-approved product and the syringe kits most often distributed in the community require that a caregiver assemble the needle using different components from different manufacturers.
How does it work?
Evzio is what this pharmacologist and former pharmacy professor would call “nifty.” The prescribed carton consists of two, electronic voice-directed automatic injectors of a single dose of naloxone together a similar trainer device to be used up 1,000 times for caregivers or family members to practice using the product. The product is designed to automatically give a intramuscular or subcutaneous injection of 0.4 mg naloxone by simply holding it to a person’s thigh, even over clothing.
The trainer device is shaped exactly like the actual naloxone injector but has a distinctly different color scheme to prevent accidental use during an overdose situation. Moreover, upon activation, the voice instructions will begin with, “This trainer can be used for practice purposes.” According to company leadership, pre-approval testing showed that 90% of volunteers properly administered the dose to a victim in an artificial, opioid overdose situation.
As for the yellow colored, naloxone auto injector, it’s about as large as a credit card and as thick as a cell phone. If an opioid overdose is suspected in a friend or other loved one, the caregiver removes the injection apparatus from the case and a battery-powered electronic voice module provides instructions. The user is instructed to removes the red safety clip and holds it to the patient’s thigh. It takes about five seconds for the needle to extrude from the apparatus, administer the dose, then retract back into the module. The voice even counts down, “5, 4, 3, 2, 1″ and informs the user when to remove the device after a click and hiss are heard./>/>
While a video demonstration is not yet available, the site for the company’s first product, Auvi-Q® epinephrine for injection, has a three-and-a-half minute video showing the proper use of this product , intended for use in severe allergic reactions that cause anaphylactic shock.
So how does a caregiver know if their loved one is experiencing an opioid overdose? These are the patient instructions for Evzio:
Signs and symptoms of an opioid emergency may include:
• unusual sleepiness and you are not able to awaken the person with a loud voice or rubbing firmly on the middle of their chest (sternum)
• breathing problems including slow or shallow breathing in someone difficult to awaken or they look like they are not breathing
• the black circle in the center of the colored part of the eye (pupil) is very small, sometimes called “pinpoint pupils” in someone difficult to awaken
Company officials said today that if a friend or caregiver is about to call 911 because they’re that worried about an unconscious person, Evzio should be given. If the situation is not due to opioids, the naloxone injection should have no other effect. In an opioid-tolerant individual, the injection may precipitate an acute withdrawal syndrome. But in all cases, the caregiver should summon medical help. Multiple injections may be necessary to continue to revive the patient until medical help arrives.
It’s important to note that even if a person doesn’t die from an opioid overdose, the respiratory depression cause by high doses of these drugs could deprive the brain of oxygen long enough to cause long-term damage.
Likely more expensive than current, unapproved naloxone kits
Unfortunately, kaléo officials were unprepared to discuss pricing of the product despite repeated questions from reporters during a media conference call today. While company officers cited that the unexpected early approval came ahead of their decisions on pricing structure, it was disappointing that they were unable to offer even an early ballpark figure.
Eric Edwards, MD, PhD, Chief Medical Officer of kaléo, said “We are very, very focused on assuring that Evzio is available to all patients that may benefit from it.”
Dr. Edwards added, “In fact, we’re working with the Harm Reduction Coalition and other not-for-profits [who] have a patient assistance program, all to assure that patients, no matter of their situation can get access to the Evzio product.”
Of course, no other similar product is officially approved for naloxone use outside the healthcare setting. The technology is also easy-to-use and far less cumbersome than trying to assemble and fill a syringe. As a former self-injector of allergy desensitization shots, I can say that it takes a bit of emotional composure for an untrained person to administer an injection. Taken together, I can appreciate the current reticence to give reporters an estimated price today, especially when a typical dose of naloxone for injection is about $45.
But we might get a feel for the price when looking at the currently marketed Auvi-Q epinephrine autoinjector. For a kit with two autoinjectors (but no practice injector), current U.S. retail pharmacy prices range from $410 to $456 without insurance coverage, or $361 with a discount. These prices are according to the pharmacy search website, GoodRx , self-described as, “an Orbitz for prescription drugs.”
With this product specifically approved for non-healthcare settings, it’s highly likely that most insurance carriers will provide some degree of coverage. But pricing for uninsured or indigent populations will most certainly rely on the partnership with harm reduction organizations. The company anticipates that Evzio might be prescribed at the same time as an opioid pain prescription, particularly for chronic pain patients who are most at risk for overdose even when using the medicine as directed.
Interestingly, the company was founded by Edwards and his twin brother, Evan, who experienced life-threatening allergies as kids (to peanuts, tree nuts, seafood and eggs) and carried epinephrine injector pens with them at all times. They found these products cumbersome to use and difficult to carry all the time and originally conceived of what became Auvi-Q when they were teenagers.
Kaléo relies on patient input for product design through to the finished product, an approach that they call Human Factors Engineering (HFE). They continue to seek other product areas where patient obstacles for life-saving medicines can be overcome.
The company is currently assembling a small sales and education force in anticipation of Evzio’s release this summer.
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