Zogenix Inc., a pharmaceutical company commercializing and developing products for the treatment of CNS disorders and pain, has submitted a New Drug Application (NDA) for its lead investigational product candidate Zohydro (hydrocodone bitartrate extended-release capsules) to the US Food and Drug Administration (FDA) for the treatment of chronic pain.
Zohydro is a novel, oral, single-entity (without acetaminophen) extended-release formulation of various strengths of hydrocodone intended for administration every 12 hours for around the clock management of moderate to severe chronic pain. If approved, Zohydro 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. Zohydro, classified as a Drug Enforcement Agency (DEA) Schedule II drug product, would carry more strict prescription and dispensing rules as compared to the currently available hydrocodone combination products. In addition, Zogenix has included in the NDA a comprehensive Risk Evaluation and Mitigation Strategy (REMS) that is consistent with current FDA and industry-wide guidelines for extended-release opioid products. The REMS is intended to control inappropriate prescribing, misuse and abuse of extended-release opioids while maintaining patient access to essential pain medications.
“The NDA submission for Zohydro is a significant milestone, bringing us another step closer to making this important acetaminophen-free hydrocodone treatment option available to patients in need of around the clock therapy for chronic pain,” said Stephen Farr, PhD, president and chief operating officer of Zogenix. “Hydrocodone is often a physician's first opioid recommendation for treating acute, moderate or moderately severe pain. However, many patients are being treated with hydrocodone combination products that include acetaminophen and, when used in high dosages or over long periods of time, put themselves at risk for developing liver injury. Zohydro could provide a significant new treatment alternative that does not contribute to this health risk.”
The NDA submission is based on data from over 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. Study 801 successfully met its primary efficacy endpoint, demonstrating that Zohydro 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 per cent 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 compared to placebo. The study demonstrated that Zohydro was generally safe and well tolerated. Overall, the most commonly reported adverse events (greater than or equal to 2 per cent ) 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 for up to 12 months, further demonstrated that Zohydro was generally safe and well tolerated, and the incidence of adverse events was consistent with that seen in the pivotal phase III efficacy study.
In conjunction with Zohydro's NDA submission, Zogenix is required to make a milestone payment of $1.0 million to Alkermes Pharma Ireland Limited (APIL), a subsidiary of Alkermes, plc, under the Company's exclusive license agreement with APIL in the US for Zohydro.
Zohydro uses APIL's 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. It 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.