Xarelto/JNJ
As if to preempt the Xarelto sNDA submission, Public Citizen is campaigning to stave off approval on grounds the ROCKET-AF study was seriously flawed. Although I have heard many of these criticisms, I wonder what is the motive or agenda of Public Citizen? Are they interested in costs, wanting to avoid expensive new drugs with marginal advantages?
Urche
Public Citizen urges FDA not to approve rivaroxaban for use in AF
Oct 21, 2011 Sue Hughes
Washington, DC - The US consumer group Public Citizen is stepping up its pressure on the US Food and Drug Administration (FDA) to not approve the new oral anticoagulant rivaroxaban (Xarelto, Bayer/Johnson & Johnson) for stroke prevention in patients with atrial fibrillation (AF) [1].
In an October 20, 2011 letter to the agency [1], Public Citizen said that there are several areas of uncertainty in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial, a large-scale study of the drug in this indication, which raise questions as to whether rivaroxaban is as safe and effective as warfarin.
The organization says that the trial "had a suboptimal control arm, showed a possible rebound excess in stroke occurrence following rivaroxaban discontinuation, tested only one dose of the study drug with no rationale as to why the chosen dose was used, and involved ethical concerns related to study protocol and conduct."
Although the FDA's Cardiovascular and Renal Drugs Advisory Committee did end up recommending approval of rivaroxaban for this indication (by a nine to two majority with one abstention) at a meeting held on September 8, 2011, Public Citizen points out that the FDA's three clinical reviewers said the drug should not be approved unless the manufacturer conducts further studies to support the efficacy and safety of rivaroxaban over appropriately managed warfarin therapy.
The group also notes that several committee members—although voting affirmatively—expressed "serious reservations", recognizing there were still unanswered questions that they were relying on postmarketing studies to resolve and proposing that rivaroxaban be restricted a third-line drug.
"With so much uncertainty as to whether rivaroxaban is truly as safe and effective as existing therapy to prevent such strokes, and with two drugs already available to treat this condition, the FDA must not rush to approve rivaroxaban for such a broad use," states the consumer group in its letter.
They also say that the FDA should follow the recommendations of its expert reviewers and reject the new request to approve rivaroxaban to prevent strokes until the drug's manufacturers conduct another, better-designed clinical trial.
It also urged the FDA to investigate the design and conduct of the ROCKET-AF trial and the manufacturer's failure to provide certain patients with the appropriate standard of care. These concerns relate to the "unjustified decision" to test a single, once-daily dose of rivaroxaban, "despite evidence from previous studies that a twice-daily regimen was safer" and "the failure to provide adequate warfarin therapy during and after the trial," which Public Citizen says "exposed patients to life-threatening risks."
The FDA's decision on rivaroxaban for the stroke/AF indication is expected on or before November 4.
Source
1. Public Citizen. Letter to the FDA in response to new drug application (NDA) #202439. October 20, 2011. Available here.
