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 less than 10% 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 among physicians managing the pain of cancer patients indicates that ARX-02 could capture approximately a quarter of the cancer breakthrough pain prescriptions. In this research, ARX-02 was predicted to take share equally from both the immediate release oral products and the transmucosal products. Given the 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 diversion or abuse. ARX-02 is designed to improve the treatment of cancer breakthrough pain while adding a substantially heightened level of detection and deterrence around prescription opioid use, misuse and abuse. ARX-02 is being developed with a range of NanoTab dosage strengths to meet the various needs of opioid-tolerant patients.
Key Potential Benefits of ARX-02 as compared to current BTP products in the market are:
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 | Unmet Need Current BTP Products |
|---|---|
| Rapid onset of pain relief (10 minutes after dosing in Phase 2 clinical studies). | Oral transmucosal fentanyl-based (OTFC) products (i.e., Actiq, Fentora, and Onsolis), the only approved treatments for cancer BTP in the United States, have shown analgesia as different from placebo as early as 15-30 minutes after dosing.3-5 |
| Improved pharmacokinetics with a more consistent Tmax (time to maximum plasma concentration) and a shorter elimination half-life, more closely matching the timing of a BTP episode. This minimizes over-medication once the pain flare has resolved and allows for safer redosing during subsequent BTP events. | OTFC products have elimination half-lives of 6 to 14 hours to treat a cancer breakthrough pain event that typically lasts 15 to 60 minutes3-5. Also, these OTFC products report inconsistent Tmax that ranges from 20 to 240 minutes, and can result in erratic onset of action and the potential for dose-stacking. |
| Effective and well tolerated for the management of BTP. The majority (86%) of patients achieved an effective and tolerable dose during titration in Phase 2. | With existing BTP products, a high proportion of patients (25% of Actiq, 35% of Fentora, and 46% of Onsolis) failed to find a dose that provides efficacy with acceptable side effects.3-5 |
| Packaging technology that enhances patient safety by reducing the possibility of misuse or abuse, while providing healthcare professionals with usage data. | AcelRx is not aware of existing BTP products which have dose tracking or abuse-deterrent features. |
| No application site reactions. | With existing BTP products, patients report application site reactions such as tooth decay (Actiq) and mouth ulcers (Fentora)3,4. |
| ARX-02 provides sufentanil, an alternative opioid for treatment of for BTP. Sufentanil may provide efficacy and/or safety advantages in certain patient populations. | All existing BTP products are fentanyl-based products with very similar product profiles. Alternatives are not available for patients who fail to achieve acceptable analgesia and have side effects with existing products. |
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