FDA actions

FDA actions

The FDA has concluded a safety review of dabigatran (Pradaxa) and found that the drug is not associated with more serious bleeding events than warfarin. The review was done using insurance claims and data from the FDA's Sentinel Initiative. According to the FDA, the bleeding rates are consistent with the observations from large clinical trials, including RE-LY, which showed that bleeding rates in patients newly started on dabigatran were similar to rates associated with new use of warfarin. Therefore, the FDA has not changed its recommendation regarding dabigatran (FDA Drug Safety Communication, Nov. 2, 2012). The next day, The New York Times published an article reporting that dabigatran has been associated with more than 500 deaths in the United States since it was introduced. It also detailed several tragic cases of bleeding deaths associated with the drug. The article indicts the FDA stating "... the approval process was not sufficiently rigorous because it allowed a potentially dangerous drug to be sold without an option for reversing its effects." The article also mentions more than 100 lawsuits that have been filed in federal courts "...and thousands more are expected" (The New York Times Nov. 3, 2012:B1).

The FDA has expanded the approval of rivaroxaban (Xarelto) to include treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), both for acute treatment and prevention of recurrence. The drug is already approved for prevention of DVT and PE after knee and hip replacement surgery and for prevention of stroke in patients with non-valvular atrial fibrillation. It is the first oral drug approved to treat DVT and PE since warfarin was approved 60 years ago; but unlike warfarin, rivaroxaban can be used as monotherapy from diagnosis until treatment is discontinued. Approval was based on three studies of nearly 9500 patients with DVT or PE randomized to rivaroxaban, enoxaparin/vitamin K antagonist, or placebo. Rivaroxaban was equivalent to enoxaparin/vitamin K antagonist and superior to placebo for preventing recurrent DVT or PE.

The FDA has approved a new egg-free flu vaccine for adults. The vaccine is manufactured using cultured mammalian cells instead of fertilized chicken eggs. The manufacturer claims that the cell culture technology enables a rapid response to public health needs, such as a pandemic, since cell culture technology allows vaccines to be manufactured within weeks as opposed to traditional flu vaccines that depend on a large number of fertilized chicken eggs to grow the virus. Cell culture technology is used for several other vaccines including polio, rubella, and hepatitis A vaccines. Approval was based on a randomized, controlled clinical study of 7700 adults ages 18-49. The new vaccine was 83.8% effective in preventing influenza when compared to placebo. Injection site reactions are the most common side effects. The new vaccine is marketed as Flucelvax by Novartis.

The FDA has approved the first Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib, dosed orally twice a day, is approved for RA patients who have failed methotrexate. The drug will compete with the parenteral RA drugs adalimumab (Humira), etanercept (Enbrel), and infliximab (Remicade). Tofacitinib carries a boxed warning regarding the increased risk of opportunistic infections, tuberculosis, cancers, and lymphoma; increases in cholesterol and liver enzymes; and decreases in blood counts. Approval was based on seven clinical trials in which the drug showed improvements in clinical response and physical function compared to placebo in patients with moderate-to-severe RA. Tofacitinib will be marketed by Pfizer as Xeljanz. The cost is projected to be just over $2000 per month, similar to other non-methotrexate biologic treatment options.