The US Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for Zogenix's Zohydro ER (hydrocodone bitartrate extended-release capsules), lead investigational product candidate for the treatment of moderate to severe chronic pain. Under the Prescription Drug User Fee Act (PDUFA), the goal for a standard review of an NDA is 10 months from NDA submission, and the has assigned a target action date of for the Zohydro ER NDA.

Zohydro ER is an oral, single-entity (without acetaminophen) novel extended-release formulation of various strengths of hydrocodone intended for administration every 12 hours for continuous, around-the-clock management of moderate to severe chronic pain for an extended period of time. If approved, Zohydro ER could be the first hydrocodone product to offer the benefit of less frequent dosing and the ability to treat patients with chronic pain without the risk of acetaminophen-related liver injury. Currently, hydrocodone is only available in immediate-release, combination products, most commonly with the analgesic acetaminophen, and requires dosing every 4 to 6 hours. Based on a recent discussion with the FDA, we anticipate the agency will convene an advisory committee for Zohydro ER during the PDUFA review period. The advisory committee provides the FDA with independent expert advice and recommendations; however, the final decision regarding approval is made by the FDA.

“We are pleased with the decision by the FDA to accept our submission for filing and look forward to working with them throughout the regulatory process,” said Stephen Farr, PhD, president and chief operating officer of Zogenix. “If approved, Zohydro ER will be classified as a Drug Enforcement Agency (DEA) Schedule II drug, subject to stricter prescribing and dispensing rules compared to the currently prescribed hydrocodone products. In addition, the Risk Evaluation and Mitigation Strategy (REMS) for Zohydro ER will be consistent with the recently introduced FDA-approved REMS for Extended Release and Long Acting Opioids. We are supportive of these measures to reduce the inappropriate prescribing and misuse of opioid products which, by including the hydrocodone class, creates consistent controls across all extended release opioid products. The approval of Zohydro ER would allow appropriate DEA registered physicians to treat chronic pain patients using hydrocodone for moderate to severe pain while avoiding acetaminophen-related liver injury.”

The NDA submission is based on data from more than 1,100 patients with chronic pain participating in the pivotal phase III efficacy study (Study 801) and an open-label phase III safety study (Study 802) of Zohydro ER. Study 801 successfully met its primary efficacy endpoint, demonstrating that Zohydro ER resulted in significantly (p=0.008) improved chronic pain relief compared to placebo. The two key secondary endpoints in this study (the proportion of patients with at least 30% improvement in pain intensity and the improvement of overall satisfaction of medication) were also met. Additional study endpoints were supportive of the efficacy of Zohydro ER compared to placebo. The most commonly reported adverse events (=2%) in the placebo-controlled pivotal phase III efficacy Study 801 in opioid-experienced patients were consistent with those typically seen with chronic opioid therapy and were constipation, nausea, somnolence, fatigue, headache, dizziness, dry mouth, vomiting and pruritus. Study 802, in which patients received Zohydro ER for up to 12 months, demonstrated that the incidence of adverse events with Zohydro ER for up to 12 months was consistent with that seen in the pivotal phase III efficacy study.

Zohydro ER is an oral, single-entity, novel extended-release formulation of hydrocodone without acetaminophen for the management of moderate to severe chronic pain in patients requiring continuous, around the clock opioid therapy for an extended period of time. If approved, Zohydro ER could be the first single-entity hydrocodone therapy for pain, avoiding the potential for liver injury associated with the use of acetaminophen in high doses or over long periods of time.

Zohydro ER uses patented Spheroidal Oral Drug Absorption System (SODAS) drug delivery technology, which serves to enhance the release profile of hydrocodone to provide extended-release pain relief relative to existing immediate-release combination products.

Chronic pain is defined as ongoing or recurrent pain that adversely affects an individual's well-being. An estimated 116 million people in are burdened with chronic pain, at an estimated national economic cost of annually.

Chronic pain can be treated with both immediate-release and extended-release opioids. Currently marketed hydrocodone products are only immediate-release and contain an analgesic combination ingredient, primarily acetaminophen. Acetaminophen may cause liver injury when used in high dosages, over long periods of time or in accidental overdoses due to multiple acetaminophen products being taken at once.

Zogenix is a pharmaceutical company commercializing and developing products for the treatment of central nervous system disorders and pain.