A world of trouble and complications are coming to bear on Xyrem (gamma hydroxybutyrate, or GHB), an orphan drug indicated for narcolepsy, marketed by Jazz Pharmaceuticals (Palo Alto, CA). The drug, a powerful depressant, is a DEA-listed Schedule III narcotic, and has been abused in “date rape” cases, among others. It was approved in 2002 with a then-current RiskMAP (mitigation action plan) that included, among other things, a black-box warning.
Last May, the company received a warning letter from FDA about unreported deaths—an obviously “serious adverse event” that is supposed to be reported to FDA within 15 days. In response to FDA, and then in its 10Q financial report at the end of June, the company pointed a finger at Express Scripts Specialty Distribution Services (St. Louis), its exclusive distributor, stating that adverse events “had not always been reported to us” in accordance with its procedure. As reported on the blog Pharmalot, Express Scripts, not exactly disagreeing, said that it “has worked closely with Jazz Pharmaceuticals over the past several months” to address the FDA concerns. But FDA, in an Oct. 11 warning letter, says that Jazz’ response “lacks sufficient corrective actions” and the problems still need to be addressed.
It turns out that this has been an ongoing dispute between Jazz and FDA; similar warning letters were sent in 2007. And behind that is the fact that the 2002 RiskMAP is still under discussion with FDA to convert it to the REMS program that has replaced RiskMAP; Xyrem is still not included on FDA’s list of current REMS. GHB has been around for decades; the Jazz patent exclusivity expires a year from now, and a year ago, according to Jazz’ June 10Q, Roxane Laboratories filed a Paragraph IV ANDA to produce a generic therapy, and the two companies are now in court. At this point, it’s hard to say which will happen first: Jazz fixing its RiskMAP/REMS, or the generic appearing on the market.