Evzio (naloxone auto-injector) / Kaleo - LARVOL DELTA

Mechanistic pharmacokinetic-pharmacodynamic modeling and simulations of naloxone auto-injector 10 mg reversal of opioid-induced respiratory depression. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Mechanistic OIRD PK-pharmacodynamic (PD) models were constructed using published data for buprenorphine, morphine, and fentanyl. A second dose of 10 mg naloxone, administered 60 min post-opioid exposure, expedited recovery to 85% of baseline ventilation and delayed time to renarcotization compared with a single dose. In addition, when 10 mg naloxone was administered at 5, 15, 30, or 60 min before fentanyl or carfentanil exposure, rapid and profound OIRD was prevented."

Journal • PK/PD data • CNS Disorders • Depression • Mood Disorders • Psychiatry

Trends in Out-of-Pocket Costs for Naloxone by Drug Brand and Payer in the US, 2010-2018. (PubMed, JAMA Health Forum) - "Throughout the period, the mean OOP costs paid by uninsured patients were higher for Evzio at $1089.17 (95% CI, $884.17-$1294.17) compared with $73.62 (95% CI, $69.24-$78.00) for Narcan and $67.99 (95% CI, $61.42-$74.56) for generic naloxone. In this observational study, the findings indicated that the OOP cost of naloxone had been an increasingly substantial barrier to naloxone access for uninsured patients, potentially limiting use among this population, which constituted approximately 20% of adults with opioid use disorder."

Journal • Addiction (Opioid and Alcohol) • Substance Abuse

Naloxone Auto-injector as a Universal Precaution for Patients With Opioid Substance Use Disorder (clinicaltrials.gov) - P=N/A | N=402 | Completed | Sponsor: University of New Mexico | Unknown status ➔ Completed

Trial completion

Rapid Reversal of CNS-Depressant Drug Effect Prior to Brain Death Determination (clinicaltrials.gov) - P1; N=0; Withdrawn; Sponsor: Prisma Health-Midlands; N=40 ➔ 0; Trial completion date: Jun 2020 ➔ Jul 2021; Recruiting ➔ Withdrawn; Trial primary completion date: Dec 2019 ➔ Jul 2021

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Cardiovascular • CNS Disorders • Vascular Neurology

Economic burden of pediatric prescription opioid poisonings in the United States. (PubMed, J Manag Care Spec Pharm) - "The authors declare no conflicts of interest or financial interests. Portions of this study were presented as an abstract at the 22nd Annual ISPOR Meeting; May 22, 2017; Boston, MA."

Clinical • HEOR • Journal • Cardiovascular • CNS Disorders • Depression • Epilepsy • Pediatrics • Psychiatry • Respiratory Diseases

[VIRTUAL] Naloxone availability throughout California (WSMRF 2021) - "Of those pharmacies 75% carried Narca"

Addiction (Opioid and Alcohol) • CNS Disorders

An open-label, randomized, single-dose, two-period, two-treatment crossover bioavailability study comparing 5 mg/0.5 mL of intramuscular naloxone hydrochloride to 2 mg/0.4 mL intramuscular naloxone hydrochloride autoinjector in healthy subjects. (PubMed, J Opioid Manag) - "There has been a dramatic increase of deaths due to synthetic opioids such as fentanyl, some requiring multiple doses of naloxone for reversal of opioid tox-icity. These results are consistent with the study rationale that indicated higher doses of intramuscular naloxone hy-drochloride would result in higher C and AUCs. These PK characteristics may be desirable for reversing opioid toxicity caused by the higher, more potent synthetic opioids."

Clinical • Journal • Addiction (Opioid and Alcohol) • CNS Disorders

FDA to speed review of generic versions of opioid overdose antidote (Regulatory Focus) - "The US Food and Drug Administration (FDA) on Monday said it would prioritize and expedite the review of generic versions of drugs indicated for the emergency treatment of opioid overdoses....FDA says it will expedite the review of all abbreviated new drug applications (ANDAs) that reference new drug applications (NDAs) for drugs indicated for the emergency treatment of known or suspected opioid overdose. The NDAs include the Narcan injection and nasal spray, Evzio auto-injector...New original naloxone ANDAs will be prioritized and may be eligible for enhanced communication too...FDA adds."

ANDA

Take-Home Naloxone and Opioid Reversals – One-Year follow-up at Opioid Treatment Program (ASAM 2020) - "We recruited adult patients (≥ 18 years of age) with OUD receiving methadone, buprenorphine or naltrexone as a medication-assisted treatment (MAT)...Once enrolled, study participants received education on opioid overdose and were prescribed two naloxone autoinjectors at their initial visit...This study demonstrates the importance of take-home naloxone at an OTP setting, as take-home naloxone provides community members with direct access to naloxone in the event of an overdose. Therefore, the authors believe policy makers should consider making take-home naloxone a mandatory component of every OTP to prevent opioid overdose deaths in the community."

Trends and economic drivers for United States naloxone pricing, January 2006 to February 2017. (PubMed, Addict Behav) - "These cumulative increases totaled 2281% for the 0.4 MG single-dose products, 244% for the 2 MG single-dose products, 3797% for the 4 MG multi-dose products, and 469% for the 0.4 MG Evzio auto-injector. We believe that increased demand for naloxone from the opioid epidemic may explain the more gradual price increases for the 0.4 MG single-dose and 4 MG multi-dose products prior to 2012. On the other hand, we believe that the sudden, sustained prices increases occurring for all of the products since 2012 may be the result of a drug shortage for the 0.4 MG single-dose products and the fact that each naloxone product has historically been sold by only a single competitor."

Journal • Pricing

Rising price of naloxone restricts accessibility (Telegram.com) - "While naloxone effectively reverses the effects of an opioid overdose, medical experts said the rising price of one form of the drug may limit overall access to the life-saving medicine....Rising prices of pharmaceuticals is a challenge insurance companies face every day....BCBS requires no co-payment or prescriptions on two naloxone products, including Narcan’s nasal spray and injection. It does not cover Evzio’s auto-injection system."

Pricing

An Observational Study of Retail Pharmacy Naloxone Prescriptions: Differences Across Provider Specialties and Patient Populations. (PubMed, J Gen Intern Med) - "Our findings reflect a need to better understand barriers to uptake of naloxone prescribing behavior among physicians and other prescribers to ensure individuals have adequate opportunity to receive naloxone from their treating clinicians."

Clinical • Journal • Observational data

"In which @Surgeon_General demonstrates how to use a naloxone auto-injector at @Medscape. https://t.co/gpl5LFvDCW" (@ivanoransky)

Implementation and evaluation of an opioid overdose education and naloxone distribution (OEND) program at a Veterans Affairs Medical Center. (PubMed, Subst Abus) - "OEND educated 30% of the Veterans referred into the program via the consult service, the majority of whom were at a relatively low risk for opioid overdose."

Journal

Government Patent Use to Address the Rising Cost of Naloxone: 28 U.S.C. § 1498 and Evzio. (PubMed, J Law Med Ethics) - "§ 1498, a section of the federal code that allows the government to use patent-protected products for its own purposes in exchange for reasonable compensation, could be used to procure generic naloxone auto-injectors, or at least bring Kaléo to the negotiating table. Precedent exists for the use of § 1498 to procure pharmaceuticals, and it could give meaning to the federal government's recent declaration of a public health emergency around the opioid epidemic, discourage new market entrants from charging exorbitant prices, and yield important public health benefits."

Journal • Pricing

The feasibility of employing a home healthcare model for education and treatment of opioid overdose using a naloxone auto-injector in a private practice pain medicine clinic. (PubMed, Curr Med Res Opin) - "Twenty withdrew because their insurance declined coverage for the naloxone auto-injector. Those completing home health showed a statistically significant difference in their ability to correctly identify the steps needed to effectively respond to an overdose p = 0.03 Preliminary evidence would suggest training on overdose symptom recognition and proper use of prescription naloxone for treatment in the home setting by home health staff would prove more beneficial than the clinic setting, but feasibility was hindered by unaffordable costs related to insurance coverage limitations."

Journal

Adamis Pharmaceuticals announces presentation of ZIMHI data at IHV scientific meeting (GlobeNewswire) - "Adamis Pharmaceuticals Corporation...announced today the presentation of data pertaining to its investigational high dose naloxone product (ZIMHI) at the Institute of Human Virology (IHV) meeting...in a session on 'Opioid Intersection'....The Adamis data was presented by Dr. Ronald Moss, Chief Medical Officer at Adamis....Adamis presented data comparing the pharmacokinetics of ZIMHI to current doses of naloxone products (Evzio, Narcan, and generic Naloxone). ZIMHI had significantly higher and more rapid levels of naloxone in the blood compared to the other products....ZIMHI was shown in the model to rapidly compete out fentanyl from the receptors in the brain while current doses took longer."

PK/PD data • Preclinical

Adamis Pharmaceuticals Announces Presentation Pertaining to Its High Dose Naloxone Product Candidate at IHV Scientific Meeting (GlobeNewswire, Adamis Pharmaceuticals Corporation) - "Adamis Pharmaceuticals Corporation...announced today that Dr Ronald Moss, Chief Medical Officer, will be presenting data on October 4, 2019, pertaining to the company’s investigational high dose naloxone product candidate (ZIMHI) at the Institute of Human Virology (IHV) meeting (http://www.ihv.org/ihvmeeting/Program/) in a session on 'Opioid Intersection'. Naloxone is an opioid antagonist that competes opioids off their receptors in the brain. Dr Moss will be presenting data comparing the pharmacokinetics of ZIMHI to current doses of commercial naloxone products (Evzio, Narcan, and generic Naloxone). Additionally, Dr Moss will be presenting data on a model that simulates drug overdoses due to the more potent synthetic opioids such as fentanyl."

Clinical • Regulatory

Statement on continued efforts to increase availability of all forms of naloxone to help reduce opioid overdose deaths (FDA News) - "There are three FDA-approved forms of naloxone – injectable, auto-injector and nasal spray – and all three currently require a prescription, which can be a barrier for people...The FDA is working with other federal, state and local officials as well as health care providers, patients and communities across the country to increase availability of all forms of naloxone...several efforts are underway at the FDA to make naloxone more readily available and accessible."

FDA event

An Innovative Model for Naloxone Use Within an OTP Setting: A Prospective Cohort Study. (PubMed, J Addict Med) - "This study validates that naloxone is not commonly used on the index study participant, but is often used on a secondary target among people who inject drugs. The large number of overdose reversals reported in this prospective study suggests that this novel model for naloxone use may be replicated at other OTP settings to reduce opioid overdose deaths.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4."

Journal

Battling the opioid abuse crisis in Colorado - '"We’re following the Surgeon General’s lead by encouraging Coloradans to understand how important it is to know what naloxone is, how to use it, how to purchase it, and to keep it in your home, car or on your person so it’s available when needed,' said Robert Valuck, PhD, RPh..."

Media quote

Adamis Pharmaceuticals Provides Update on Litigation with kaléo Inc. (GlobeNewswire, Adamis Pharmaceuticals Corporation) - "Adamis Pharmaceuticals Corporation...today provided an update on the litigation with kaléo Inc regarding kaléo’s claims of patent infringement relating to Adamis’ higher dose naloxone injection product (ZIMHITM), as well as, new claims brought by Adamis against kaléo regarding its use of Adamis’ SYMJEPITM trademark. On Friday, June 21st, the company filed two motions in the United States District Court for the District of Delaware in response to kaléo’s patent infringement lawsuit relating to ZIMHI. Adamis filed an amendment to its original new drug application (“NDA”) removing any reference to kaléo’s EVZIO® product, which Adamis contends prevents kaléo from claiming infringement under the Hatch-Waxman Act. § 1125(a), and common law unfair competition and trademark infringement for kaléo’s use of Adamis’ SYMJEPI trademark."

Clinical • Corporate lawsuit

Rutgers study finds 'Narcan deserts' in NJ's largest cities (PATCH) - "People living in some of New Jersey's largest cities have less access to lifesaving opioid overdose drugs than those in smaller, wealthier towns, Rutgers University researchers say....A study that analyzed how a city's 'population and affluence' correlated with the availability of naloxone in retail pharmacies....The study compared naloxone availability in 90 retail pharmacies in 10 New Jersey cities...over a five-month period....'This shows that New Jersey has naloxone 'deserts' where the medication is needed most.'"

HEOR

Plasma levels of naloxone compared using various administration methods (eMPR) - P=PK/PD, N=30; "According to the results of a recently published study, FDANxSpray...was found to yield higher plasma concentrations of naloxone compared to other devices used to treat opioid overdoses....aimed to compare the pharmacokinetics (PK) of the two FDA-approved naloxone devices (Evzio and FDANxSpray) to the non-FDA approved improvised nasal naloxone device (INND)....FDA-approved 4-mg FDANxSpray should be considered...based on its ease of use as well as its ability to produce higher plasma concentrations."

PK/PD data

Study finds vast differences in ease-of-use for naloxone delivery methods (PRNewswire) - "Design Science Consulting, Inc., today announced results from a comparative analysis have determined that NARCAN® Nasal Spray is easier for non-medical personnel to administer than a prefilled syringe. The full study, entitled 'Comparative Human Factors Evaluation of Two Nasal Naloxone Administration Devices: NARCAN® Nasal Spray and Naloxone Prefilled Syringe with Nasal Atomizer,' was published in Pain and Therapy."

Clinical data