ARX-02 Sufentanil NanoTab® Breakthrough Pain (BTP) Management System
According to published data, in 2006 approximately 700,000 cancer patients in the United States experienced episodes of pain that "breaks through" the regular baseline pain medication.1 Typically, this breakthrough pain (BTP) reaches maximum intensity within 5-10 minutes after onset, and the pain flare lasts 15-60 minutes.1 The occurrence of these BTP episodes is unpredictable, and patients may experience several episodes per day.
The prescription volume for oral transmucosal products for the management of cancer BTP is estimated to be 220,000 prescriptions per year. This suggests that a minimal number of cancer patients with BTP are treated with approved transmucosal BTP medications. In addition, many physicians use immediate release oral opioids to treat cancer BTP. This market may be larger than the transmucosal product market. Market research with physicians managing the pain of cancer patients indicated a positive reaction to the ARX-02 product profile and the potential benefits of ARX-02 compared to currently available products, ARX-02 may represent a significant commercial opportunity.
The ARX-02 Sufentanil NanoTab™ BTP Management System is a potential new treatment option for cancer patients who suffer from BTP. ARX-02 demonstrated a rapid onset of pain relief (10 minutes) in Phase 2 clinical studies. ARX-02 has a unique, consistent pharmacokinetic profile, and a shorter half-life than fentanyl BTP products. By more closely matching the half-life of sufentanil with the duration of a BTP episode, we believe the potential for over-medication with ARX-02 after the pain flare has resolved, or dose-stacking during subsequent, use is minimized.
ARX-02 consists of a magazine containing 30 single dose applicators, or SDAs, loaded into a unique multiple SDA “smart dispenser”, or MSD. Each single dose applicator includes a sufentanil NanoTab that a patient can self-administer to their sublingual space for oral transmucosal absorption.The MSD:
- protects and dispenses SDAs, one at a time,
- displays a recent dose indicator that is designed to mitigate overdosing,
- has child resistant, elderly friendly features, and
- provides electronic date and time stamping of each SDA removal event.
The date and time event log is designed to be retrieved from the MSD by a healthcare professional during an office visit to assist the prescriber in understanding the usage profile of the medication, including looking for patterns of misuse or potential abuse. ARX-02 is designed to improve the treatment of cancer breakthrough pain while adding a substantially heightened level of monitoring for physicians to more effectively manage patient populations. ARX-02 is being developed with a range of NanoTab dosage strengths to meet the various needs of opioid-tolerant patients.
All products currently approved for the treatment of cancer BTP are fentanyl-based and have a number of limitations, including:
- inconsistent Tmax that ranges from 20 to 240 minutes, and can result in erratic onset of action and the potential for dose-stacking;
- long elimination half-lives;
- local adverse events, such as dental caries and oral mucosal irritation; and
- drug packaging that lacks effective deterrence against abuse and misuse.
| Key Potential Benefits of ARX-02 |
|---|
| Rapid onset of pain relief (10 minutes after dosing in Phase 2 clinical studies). |
| Improved pharmacokinetics with a consistent Tmax (time to maximum plasma concentration) and a short elimination half-life, closely matching the timing of a BTP episode. This could minimize over-medication once the pain flare has resolved and allows for redosing during subsequent BTP events. |
| Effective and well tolerated for the management of BTP. The majority (86%) of patients achieved an effective and tolerable dose during titration in our Phase 2 study. |
| Packaging technology that enhances patient safety by reducing the possibility of misuse or abuse, while providing healthcare professionals with usage data. |
| No application site reactions identified in studies to date. |
| ARX-02 provides sufentanil, an alternative opioid for treatment of BTP. Sufentanil may provide efficacy and/or safety advantages in certain patient populations. |
ARX-02 Development Status
AcelRx has announced positive results from a Phase 2 clinical study evaluating the safety and efficacy of ARX-02 in the treatment of cancer breakthrough pain in opioid-tolerant patients. The primary endpoint of time-weighted Sum of the Pain Intensity Difference over the first 30 minutes after dosing (SPID-30) was statistically significant for ARX-02 compared to placebo (p<0.001). In addition, AcelRx completed an end-of-Phase 2 meeting with the FDA, that defined the required criteria for Phase 3 studies with ARX-02.
References
1: Portenoy RK and Hagen NA. Breakthrough pain:definition, prevalence and characteristics. Pain 1990; 41(3):273-281
2: Zeppetella, G. Opioids for Cancer Breakthrough Pain: A Pilot Study Reporting Patient Assessment of Time to Meaningful Pain Relief. J Pain Symptom Manage 2008;35:563-567
3: Actiq package insert
4: Fentora package insert
5: Onsolis package insert
ARX-02 Publications and Press Releases
Phase 1 clinical trial results
Phase 2 multicenter, randomized, placebo-controlled, crossover study results
