We’ve noted in previous postings the failure of JAZZ to convince the FDA Advisory Committee that XYREM should be approved for fibromyalgia, and our opinion that the FDA is unlikely to approve the drug as the PDUFA Date approaches. Motley’s Brian Orelli seems to share our opinion, as do the vast majority of the people responding to his poll. It does seem meaningful to restate our position at this time, both in support of Mr. Orelli, but also to clarify the regulatory position as we see it. There were significant issues raised about the RISK associated with this product. The REMS program offered by XYREM was felt to be inadequate by the Advisory Committee. More importantly, whatever the drug does or does not do in the intended patient population, in the absence of an adequate REMS program, it increases the risk of the non-patient population with no benefit to these non-patients. The FDA mandate is to protect and promote the health of the US population. With an inadequate REMS, the FDA must protect and not approve this drug until an adequate REMS is in place.
Posts tagged ‘Xyrem’
The FDA Advisory Committee meeting is now in the history books and the hopes of JAZZ Pharmaceuticals for Xyrem having a fibromyalgia indication seem lost forever. We monitored the discussion throughout the day and were happy to see that the Panel members weren’t pulling any punches. They confirmed our August 19, 2010 opinion that the risk clearly outweighed the benefits. The only surprise of the day came when the FDA ended the voting after the Panel declared that the proposed REMS program from JAZZ was inadequate. This avoided an up and down vote on the safety of the drug. We imagine that the Panel would have voted overwhelmingly negative on the safety of the drug. Accompanying that vote would have been an equally negative dialog that would have challenged the wisdom of keeping the drug on the market. In the absence of that negative vote, FDA and JAZZ can strengthen the existing REMS program and be in a stronger position to respond to the calls to withdraw the drug which are likely to be made.
Bloomberg today announced that the FDA review of Xyrem that has been provided to the Advisory Committee members reports that the drug is safe and effective for its intended proposed use in patients with fibromyalgia. As has been reported widely, the active ingredient, gamma hydroxybutyrate, has been illegally formulated as a street drug and associated with date rapes.
The FDA review really shouldn’t come as a big surprise. The drug is currently approved as safe and effective for the treatment of narcolepsy BUT… And this BUT is the detail in which the devil usually hides. It is currently considered a Schedule III controlled substance with a well thought out, limited distribution system. Even with this rigorous control system and even with the more rigorous system of a Schedule III drug in a controlled clinical trial, it is being abused and misused by other people, and has been associated with date rape. While the diversion rate is remarkably low, so is the use of this drug. The sponsor, Jazz Pharmaceuticals Inc, reports 26,000 narcolepsy patients treated between 2002 and 2008, certainly in keeping with its Orphan Drug status of less than 200,000 patients. Fibromyalgia on the other hand represents a patient population of 5,000,000. Doing the arithmetic (5,000,000/26,000), we find this almost 200 fold increase in the exposure to represent a significant challenge to an already cumbersome distribution system. Will the FDA take the chance that approval of this drug could result in a potential 200 fold increase in the number of date rape cases reported?
Will the sponsor, Jazz Pharmaceuticals Inc, be able to jazz up the current REMS program, including the distribution system, to plug existing holes and accomodate the increased number of patients?
The Advisory Committee discussion should be interesting. We think it will focus less on efficacy and safety and more on REMS and distribution systems. We think the Panel will conclude a 200 fold increase in the potential number of date rape cases has the same negative effect on the approval of a drug as would a 200 fold increase in the number of heart attacks for any “me too” drug trying to expand its approved indication. If they don’t, the FDA will. Remember, its all about benefit/risk and benefit/risk on this one is NFC!