A blockbuster is born in J&J's Nucynta ER
This article was originally published in Scrip
Johnson & Johnson has received FDA approval for Nucynta ER in moderate to severe chronic pain. Armed with clinical trial data showing comparable efficacy and superior tolerability to the market-leading opioid OxyContin, Nucynta ER is likely to be a commercial success for Johnson & Johnson. Additional benefits in neuropathic pain will further strengthen the clinical argument for its use.
The US FDA has approved Johnson & Johnson’s opioid painkiller Nucynta ER (tapentadol extended release) for the management of moderate to severe chronic pain when a continuous around-the-clock opioid analgesic is needed for an extended period of time (scripintelligence.com, 29 August 2011). Johnson & Johnson already markets an immediate-release formulation, Nucynta, for moderate to severe acute pain, although the US approval of the twice-daily version is of greater significance to the company.
When Nucynta was first approved in 2008, it represented the first novel opioid analgesic in more than 25 years. In addition to being a mu-opioid receptor agonist, tapentadol also acts through norepinephrine reuptake inhibition, similarly to the related compound tramadol. However, unlike tramadol, tapentadol is a strong opioid and can compete with morphine and oxycodone in terms of efficacy.
Clinical studies of Nucynta ER, using Purdue Pharma's OxyContin (oxycodone controlled release) as a comparator, have confirmed the drug's potent analgesic efficacy. In a Phase III trial of patients with moderate to severe chronic low back pain, Nucynta ER and OxyContin produced placebo-subtracted reductions in pain intensity (measured on an 11-point numerical rating scale) of -0.7 and -0.8, respectively, over the study's 12-week maintenance period, with -0.8 and -0.9 point reductions at week 12. Fewer patients receiving Nucynta ER discontinued the study due to treatment-emergent adverse events (16.7% versus 31.7%) and common opioid-induced side effects such as nausea and constipation were significantly less prevalent among the Nucynta ER group. Experts in the pain field hypothesise that tapentadol's dual mode of action allows for an opioid-sparing effect and potentially limits typical opioid-induced side effects such as constipation.
Another notable problem associated with opioids, especially in the US, is their potential for misuse and diversion. This concern is underscored by the classification of strong opioids as Schedule II controlled substances by the US Drug Enforcement Agency. According to the National Institute on Drug Abuse, the number of individuals abusing pain medications for the first time quadrupled during the 1990s to 2.5 million in 2000. To counter this, drug developers are formulating tamper-resistant versions of their drugs, designed with a physical barrier to deter the common methods of abuse, such as crushing, chewing, snorting or injecting. Purdue is already selling tamper-resistant OxyContin tablets, while Johnson & Johnson has followed suit with Nucynta ER.
Questions raised about this tamper-resistant formulation were central to the FDA's initial rejection of Nucynta ER in October 2010. The FDA required data concerning the "conversion of the extended-release formulation used in clinical trials to a different extended-release formulation designed to increase mechanical resistance to breaking or crushing." Johnson & Johnson has now addressed the issues in the Complete Response Letter.
Datamonitor expects Johnson & Johnson to position Nucynta ER against OxyContin in the US market. Its favourable tolerability profile should ensure rapid uptake among patients that cannot achieve adequate pain relief due to the incidence or severity of side effects. Furthermore, Nucynta ER will benefit from the commercial backing of Johnson & Johnson, which is already a key player in the US chronic pain market. In addition to the immediate-release Nucynta, Johnson & Johnson also markets Duragesic (fentanyl transdermal patch), Ultram and Ultram ER (tramadol), Ultracet (tramadol and acetaminophen) and Jurnista (hydromorphone extended release).
Datamonitor forecasts US sales for chronic moderate to severe pain to surpass $600m. Sales in other markets, plus prescriptions for neuropathic pain, will likely see Nucynta ER attain blockbuster status. Johnson & Johnson and Grünenthal, tapentadol's originator, have shown that tapentadol is effective for treating diabetic peripheral neuropathic pain. It can be notoriously difficult for physicians to distinguish the exact aetiology of pain, and in many cases both nociceptive and neuropathic mechanisms contribute. The demonstration of efficacy in both nociceptive and neuropathic pain indications will see Nucynta ER become the drug of choice in such cases. Chronic back pain, which is estimated to be neuropathic in around one third of cases, therefore represents a substantial market opportunity for Johnson & Johnson.
Daniel Chancellor is an associate analyst in healthcare with Datamonitor