FDA Panel Recommends Tofacitinib Approval for RA

Joe Barber Jr, PhD

May 09, 2012

May 9, 2012 — The US Food and Drug Administration Arthritis Advisory Committee voted 8-2 today to recommend the approval of tofacitinib, the first selective oral Janus kinase (JAK) inhibitor to treat rheumatoid arthritis.

The 10-member panel was asked to "discuss new drug application 203214, tofacitinib tablets, Pfizer Inc., for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs)," according to background material provided before the meeting.

The committee was charged with considering 4 questions. The first question was, "Do the data provide substantial evidence of the efficacy of tofacitinib for radiographic outcomes?" On this question, 2 panel members voted yes and 8 voted no.

In voting yes, Leslie Crofford, MD, from the University of Kentucky School of Medicine in Lexington, suggested that the evidence of radiographic efficacy was substantial and that she did not interpret substantial to mean "definitive."

Conversely, in voting no, Elizabeth Smith, a patient representative from Burke, Virginia, indicated that she did not consider the evidence of radiographic efficacy to be substantial. However, in agreement with other committee members, she noted that a better answer might not be available.

The second question considered by the committee was, "Overall, do the data provide substantial evidence of the efficacy of tofacitinib for the treatment of moderately to severely active rheumatoid arthritis in patients who have had inadequate response to one or more [DMARDs]?" On this question, all 10 panel members voted yes.

The committee expressed that the data were consistent across studies. In particular, Maria E. Suarez-Almazor, MD, PhD, from the University of Texas M.D. Anderson Cancer Center in Houston, suggested that the efficacy of tofacitinib against rheumatoid arthritis was similar to that of other biologics.

The third item considered by the committee was, "Is the safety profile of tofacitinib adequate to support approval of tofacitinib for the treatment of moderately to severely active rheumatoid arthritis in patients who have had inadequate response to one or more DMARDs?" On this question, 7 panel members voted yes, 2 voted no, and 1 abstained.

In its presented materials, Pfizer proposed the availability of 5- and 10-mg doses of tofacitinib to be taken twice a day on the basis of its preclinical and clinical research. During its presentation, the FDA noted that the drug was associated with dose- and/or treatment duration-dependent increases in malignancy rates, lipid and cholesterol levels, and serious infection rates.

In abstaining, James Ware, PhD, from the Harvard School of Public Health in Boston, Massachusetts, noted that he understood the value of the drug but found its safety profile challenging. Many of the panel members who voted yes indicated a preference for the 5-mg dose, suggesting that its efficacy appeared to be similar to that of the 10-mg dose.

In addition, several panel members expressed concern that the indication for the drug was too broad. In voting no, Lenore Buckley, MD, MPH, from the Virginia Commonwealth University School of Medicine in Richmond, stated that she would have voted yes for this question if the proposal targeted a more limited patient population such as high-risk patients.

The final question discussed by the committee was, "Do the efficacy and safety data provide substantial evidence to support approval of tofacitinib for the treatment of moderately to severely active rheumatoid arthritis in patients who have had inadequate response to one or more DMARDs?" On this question, 8 panel members voted yes and 2 voted no.

Many of the panel members reiterated their preference for the 5-mg dose over the 10-mg dose and the need for longer-term safety data. In voting no, Sherine Gabriel, MD, from Mayo Medical School in Rochester, Minnesota, agreed with Dr. Buckley that the indication was too broad and said that she would have supported approval with a more limited indication.

During the open public hearing session of the meeting, David Mandel, MD, a rheumatologist from Ohio, supported the approval of tofacitinib for the treatment of rheumatoid arthritis.

"As an oral medication, tofacitinib offers some very promising advantages to patients of ours who do not have access to infusion, who are 'needle-phobic,' or who [have difficulty in traveling to the clinic for infusions]," Dr. Mandel stated during the meeting. "This medication will improve the care of our patients with rheumatoid arthritis."

The commentator has disclosed no relevant financial relationships.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....