All opioid analgesics induce respiratory depression, which is invariably the cause of death in cases of opioid overdose.  In 2015 in the US, 91 people died each day from opioid overdose, comparable to the number from car accidents or gun violence.  More than half of these deaths were from legal prescription opioid pain killers (eg. hydrocodone and oxycodone).  The US economic burden of this crisis is estimated to be greater than $78 billion annually.

Many new abuse-deterrent opioids have been approved in recent years, but all are abuse deterrent formulations (ADF) of extended release (ER) products marketed to a small number of pain specialists at premium pricing.  These ER/ADF products represent only a small fraction of the opioids consumed nationally, while generic immediate release (IR) products represent 90% of the opioid prescriptions written in the US today.  The low rate of reimbursement for these generics is a major disincentive to investment in abuse deterrent technologies, and thus NO abuse deterrent IR products are on the market today.

The Quivive answer is to combine generic IR opioids with a generic respiratory stimulant (RS) using a regulatory approach known as the 505(b)(2) submission, which affords an accelerated path to regulatory approval.  The RS will be sub-therapeutic when used as directed, but will prevent death from respiratory depression following either accidental or intentional overconsumption.  Abuse deterrence is achieved by aversion to unpleasant, but not dangerous, RS side-effects when excessive doses are consumed.  These products will be combined into a simple fixed dose tablet without complex or in-licensed technology, ensuring a low cost of goods that will support competitive pricing and acceptance and reimbursement by third party payers.

Quivive has confirmed proof of concept in animal studies and a strong IP position, with published USPTO & WO-PCT applications and additional filed provisionals.  These applications cover the fixed-dose combination of all currently approved opioids, benzodiazepines, barbiturates, and sleeping pills with any/all currently approved respiratory stimulants for delivery by oral or non-parenteral routes – ie. a platform for a future pipeline of dozens of drugs that are both abuse deterrent and safer than current options.

Generic IR hydrocodone + acetaminophen (Vicodin, Norco, Lortab, etc.) was the most prescribed drug in the US in 2013, with 137 million prescriptions written for hydrocodone containing products that year.  Generic oxycodone is the second most prescribed opioid in the US and gaining fast due to recent DEA rescheduling of hydrocodone from Category III to II.  Thus, a safer abuse deterrent replacement for these products would address a very large US market.

 Quivive’s strong IP will support development of a platform of safer and abuse deterrent products wherever respiratory depression is a concern.  The first product (QEV-817), will be a safer IR hydrocodone/acetaminophen analgesic, to be followed by development of an IR oxycodone product.  Development of other combination products will be initiated as appropriate.