Lower Risk Opioids

Although the efficacy of opioid analgesics for chronic pain is now established, there is continued concern on the part of FDA, DEA and clinicians about their safety, abuse and diversion. DEA Schedule II (C-II) strong opioids such as morphine (e.g., Embeda®, Avinza®), oxycodone (e.g., OxyContin®), oxymorphone (e.g., Opana® ER), hydromorphone (e.g., Exalgo®) and fentanyl (e.g., Duragesic® patch) are used to treat severe intractable pain; however, clinicians are frequently reticent to use such drugs for patients with pain of moderate intensity.

There is therefore a need of extended release opioid analgesics with a lower DEA schedule (e.g., C-III or C-V) to treat moderate pain when non-opioid analgesics (e.g., acetaminophen, NSAIDs, COX-2 inhibitors) fail to provide adequate pain relief. Such treatments can avoid or even delay the need for strong (C-II) opioids. According to the DEA, C-III to C-V opioids have a low potential for abuse relative to Schedule II (C-II) opioids (http://tinyurl.com/2cxnzxp). This lower abuse potential includes reduced risk for physical dependence and reduced “liking” by recreational drug users.”

In addition to the low risk of abuse, C-III opioids have practical advantages over C-II opioids. Prescriptions for C-II drugs cannot be refilled. A new prescription must be issued each time. In contrast, prescriptions for C-III drugs may be refilled up to five times in six months. Additionally, prescriptions for C-II drugs must be written and be signed by the practitioner, while prescriptions for C-III drugs may by written, phone-in or faxed.

If given a choice, clinicians are more likely to use extended release opioids which have a C-III Schedule over a C-II Schedule, particularly for moderate to moderately severe pain. There are no marketed C-III extended release opioids in the United States.

The sales of tramadol, an unscheduled opioid approved for the treatment of moderate to moderately severe pain demonstrate the potential for our C-III opioid analgesics. The total U.S. market for tramadol exceeded 27 million prescriptions in 2009, with an annual growth rate in prescriptions of 6.2%. According to Wolters Kluwer Pharma Solutions, in 2009, the market for tramadol in major markets exceeded $2 billion.

Market Potential in Moderate to Moderately Severe Pain