Opioids (or opiates) have been the gold-standard drug class for severe pain relief for millennia. Despite its maturity, the global prescription opioids market was worth in excess of $10 billion in 2008. Significant market value has been maintained in the presence of nonbranded generics over the last few decades via drug delivery reformulations (e.g., fixed dose combination, controlled-release, patch), providing both market exclusivity and the possibility of a high price point.
As a result, distinct opioid sub-markets can now be identified based on the speed and length of action, convenience, and route of delivery. One such market is the emergence of short- and rapid-acting opioid formulations specifically designed to tackle breakthrough pain.
Common in late-stage cancer patients, breakthrough pain is a transient exacerbation of pain that occurs in those with otherwise stable, baseline-persistent pain. Breakthrough pain can also afflict noncancer patients suffering from conditions such as arthritis, low-back pain, and diabetic neuropathy.
Cephalon effectively created the short- and rapid-acting opioids market in 1998 when it launched Actiq (oral transmucosal fentanyl citrate), a lollipop formulation of fentanyl indicated for breakthrough cancer pain in opioid-tolerant patients. Actiq provided both a rapid onset of action (approximately 15 minutes) and a short duration of action (approximately two hours).
Cephalon launched a follow-on product to Actiq in 2006 in the U.S. Fentora (buccal fentanyl) is an effervescent buccal formulation of fentanyl, producing a quicker onset of action than Actiq at approximately 10 minutes. Generic versions of Actiq were also launched in 2006 in the U.S., providing nonbranded competition in the short- and rapid-acting opioids market.
The global short- and rapid-acting opioids market grew to nearly $800 million in 2007; however sales of this drug class declined in 2008 to around $700 million. While a proportion of this global downturn can be attributed to generic Actiq incursion in the U.S., this cannot explain the reduction in total volume of short- and rapid-acting opioid units sold (including generics) observed in 2008.
The drop in volume sales is likely a result of reduced off-label prescribing. In 2007, Cephalon agreed to settle a large lawsuit concerning marketing of Actiq for nonapproved indications in the U.S. As a significant proportion of Actiq’s prescriptions were off-label in noncancer indications (up to 80%), this spotlight on Cephalon’s marketing practices has hit sales of its breakthrough pain franchise.
Relying on predominantly breakthrough cancer pain patients has restricted the revenue potential for Fentora when compared with Actiq a few years earlier. In addition, Cephalon severely cut promotional spending on Fentora in the U.S., possibly as a result of the heightened scrutiny regarding marketing messages and the need to ensure that only cancer breakthrough pain patients were being targeted.
In order to enhance the revenue potential of Fentora in this more stringently monitored environment, Cephalon is seeking a broad noncancer breakthrough pain indication in the U.S.
Actiq and Fentora could be useful pharmacological tools for patients suffering from noncancer breakthrough pain if managed appropriately. The off-label prescribing observed with Actiq demonstrates the demand for such medication in noncancer breakthrough pain. Although delayed, Datamonitor believes that Fentora will receive the noncancer pain label being sought, both opening up a future market and serving a clear unmet need for patients.