One of our non-generic products under development is our Rexista™ (abuse deterrent oxycodone hydrochloride extended release tablets) product candidate, intended as an abuse and alcohol-deterrent controlled-release oral formulation of oxycodone hydrochloride for the relief of pain.
Rexista™ is a new drug candidate, with a unique long acting oral formulation of oxycodone intended to treat moderate-to-severe pain when a continuous, around the clock opioid analgesic is needed for an extended period of time. The formulation is intended to present a significant barrier to tampering when subjected to various forms of physical and chemical manipulation commonly used by abusers.
It is also designed to prevent dose dumping when inadvertently co-administered with alcohol. Dose dumping is the rapid release of an active ingredient from a controlled-release drug into the blood stream that can result in increased toxicity, side effects, and a loss of efficacy. Dose dumping can result by consuming the drug through crushing, taking with alcohol, extracting with other beverages, vaporizing or injecting.
In addition, when crushed or pulverized and hydrated, the proposed extended release formulation is designed to coagulate instantaneously and entrap the drug in a viscous hydrogel, which is intended to prevent syringing, injecting and snorting.
Our Rexista™ formulation is difficult to abuse through the application of heat or an open flame, making it difficult to inhale the active ingredient from burning.
Rexista™ also contains a blue dye that is emitted once the tablet is tampered with or crushed. This stigmatizing blue dye may act as a deterrent if abused orally or via the intra-nasal route and may also serve as an early warning mechanism to flag potential misuse or abuse.
The Company filed for an NDA for Rexista™ in November of 2016. In February 2017, the FDA accepted for filing the Company’s previously announced NDA seeking authorization to market its Rexista™ (abusedeterrent oxycodone hydrochloride extended release tablets) in the 10 mg, 15 mg, 20 mg, 30 mg, 40 mg, 60 mg and 80 mg strengths. The FDA has determined that the Company’s application is sufficiently complete to permit a substantive review, and has set a PDUFA target action date of September 25, 2017. The submission is supported by pivotal pharmacokinetic studies that demonstrated that Rexista™ is bioequivalent to OxyContin® (oxycodone hydrochloride extended release). The submission also includes abuse-deterrent studies conducted to support abuse-deterrent label claims related to abuse of the drug by various pathways, including oral, intra-nasal and intravenous, having reference to the FDA's "AbuseDeterrent Opioids — Evaluation and Labelling" guidance published in April 2015.
According to Symphony Health Solutions, OxyContin® (oxycodone hydrochloride controlled-release tablets), U.S sales are at $2.1 billion for 12 months ending December 2016.
Rexista Chronological facts:
In March 2015, we announced the results of three definitive open label, blinded, randomized, cross-over, Phase I pharmacokinetic clinical trials in which Rexista™ was compared to the existing branded drug Oxycontin® under single dose fasting, single dose steady-state fasting and single dose fed conditions in healthy volunteers. We had reported that the results from all three studies showed that Rexista™ met the bioequivalence criteria (90% confidence interval of 80% to 125%) for all matrices, i.e., on the measure of maximum plasma concentration or Cmax, on the measure of area under the curve time (AUCt) and on the measure of area under the curve infinity (AUCinf).
In May 2015, the FDA provided us with notification regarding our IND submission for Rexista™ indicating that we would not be required to conduct Phase III studies if bioequivalence to Oxycontin® was demonstrated based on pivotal bioequivalence studies. In January 2016, we announced that pivotal bioequivalence trials of our Rexista™, dosed under fasted and fed conditions, had demonstrated bioequivalence to Oxycontin® (oxycodone hydrochloride) extended release tablets as manufactured and sold in the U.S. by Purdue Pharma. The study design was based on FDA recommendations and compared the lowest and highest strengths of exhibit batches of our Rexista™ to the same strengths of Oxycontin®. The results show that the ratios of the pharmacokinetic metrics, Page 14 Cmax, AUC0-t and AUC0-f for Rexista™ vs Oxycontin®, are within the interval of 80% - 125% required by the FDA with a confidence level exceeding 90%. Having now demonstrated such bioequivalence, we believe we will not be required to conduct Phase III studies although no assurance can be given that we will not be required to conduct further studies for Rexista™. The FDA notification is significant as it provides a basis for an accelerated development plan for our Rexista™ product candidate, without the need for more costly and time consuming Phase III studies. In July 2016, the FDA completed its review of our previously requested waiver of the NDA user fee related to our Rexista™ NDA product candidate. The FDA, under the small business waiver provision section 736(d)(1)(D) of the Federal Food, Drug, and Cosmetics Act, granted the Company a waiver of the $1,187,100 application fee for Rexista™.
In July 2016, the Company announced the results of a food effect study conducted on its behalf for Rexista™. The study design was a randomized, one-treatment two periods, two sequences, crossover, open label, laboratory-blind bioavailability study for Rexista™ following a single 80 mg oral dose to healthy adults under fasting and fed conditions. The study showed that RexistaTM can be administered with or without a meal (i.e., no food effect). Rexista™ met the bioequivalence criteria (90% confidence interval of 80% to 125%) for all matrices, involving maximum plasma concentration and area under the curve (i.e., Cmax ratio of Rexista™ taken under fasted conditions to fed conditions, and AUC metrics taken under fasted conditions to fed conditions). The Company believes that Rexista™ is well differentiated from currently marketed oral oxycodone extended release products.
There can be no assurance that we will not be required to conduct further studies for Rexista™, that the FDA will ultimately approve the Company’s NDA for the sale of Rexista™ in the U.S. market, or that it will ever be successfully commercialized.