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An external review of Phase III data for Javelin Pharmaceuticals' Ereska has found previously negative top-line results for its primary endpoint to be statistically significant. While the findings offer renewed hope for the company, ketamine's association with drug abuse and its well-documented hallucinatory effects represent key weaknesses in the market place, despite Ereska's proven efficacy.
Prior to the third-party reassessment of pain score measurements, Javelin Pharmaceuticals reported that Ereska (intranasal ketamine) had narrowly missed the principal goal of a late-stage trial. However, a third-party biostatistics company verified the presence of inconsistencies in the previously disclosed top-line results (based upon data captured by an external vendor), bringing renewed hope to Javelin. Indeed, the company has benefited from a share increase of around 6% since the announcement of the re-examined data.
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been in use for over 25 years as an anesthetic, although is not approved for use as a pain reliever. Nevertheless, low-dose ketamine has been used off-label for the treatment of various pain complexes and the safety and efficacy of ketamine as an anesthetic and analgesic is well documented. According to IMS Health, ketamine achieved total sales of over $8m across the seven major markets (US, Japan, France, Germany, Italy, Spain and the UK) in 2008.
Javelin is developing Ereska - an intranasal formulation of ketamine - in the US and EU as an acute treatment for moderate and severe pain. The company plans to meet with the FDA to review the trial's results and discuss the development path for the drug.
Datamonitor believes that an FDA-approved formulation of ketamine for the treatment of moderate to severe pain will provide physicians with an accepted and regulated alternative to off-label use and opioids. Breakthrough pain, which affects approximately 42% of cancer patients across the seven major markets, is typically treated with opioids. In 2008, the opioids market was valued at an estimated $9.6 billion across the seven major markets and is forecast to grow in the future as a result of the launch of rapidly acting fentanyl products. However, opioids are associated with several adverse events and patients who use opioids chronically may display tolerance. For this reason, Datamonitor believes that there is a market for a non-opioid agent to treat breakthrough pain.
That said, myriad hallucinatory and other psychomimetic effects, observed at sub-anesthetic doses in healthy volunteers, counterbalance the benefits of ketamine. Indeed, the major competitive disadvantage of ketamine is its 'dissociative' or 'hallucinogenic' effects. Pain specialists interviewed by Datamonitor support this, expressing concerns related to potential safety issues despite ketamine's potential as an alternative to opioids. Therefore, Javelin will need to carefully monitor the hallucinatory side effects of ketamine in future trials of Ereska. Pain specialists also proposed that use of ketamine and an opioid such as Actiq (fentanyl citrate; Cephalon) in combination represents an interesting avenue of research.
As the only non-opioid in the current breakthrough pain pipeline, and being of an intranasal formulation, Ereska is well positioned to compete against Cephalon's Actiq and Fentora in this market. However, a substantial challenge for Javelin will be to tackle the negative perception of ketamine as a dangerous drug that is associated with narcotics abuse. In order to overcome this barrier, Javelin would benefit from seeking the marketing resources of a larger company with experience in the narcotic analgesics market.
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