By a vote of 8 to 2, an independent arthritis advisory committee recommended in May 2012 that the U.S. Food and Drug Administration (FDA) approve a new, oral medication called tofacitinib for patients with moderate to severe rheumatoid arthritis, or RA, whose disease does not respond to at least one other currently available treatment. Tofacitinib would be the first oral disease-modifying antirheumatic drug, or DMARD, approved in more than a decade. Its effectiveness is being compared to that of biologic drugs.

Many committee members also stressed the need for long-term studies to track the drug’s safety if it does receive FDA approval.

The drug’s maker, Pfizer Inc., says it appreciates the panel’s “robust discussion” that led to the recommendation. “The RA patient population needs additional treatment options, and Pfizer looks forward to working with the FDA on next steps as it completes its review of the tofacitinib application,” Yvonne Greenstreet, MD, senior vice president and the head of Medicines Development Group for Pfizer Specialty Care, said in a written statement.

The FDA is not expected to make a final decision on tofacitinib until August. The agency is not required to follow the recommendations of its advisory committees, but generally does. Pfizer says it plans to make tofacitinib available to patients as soon as possible upon FDA approval

Tofacitinib is part of a new class of drugs known as “JAK inhibitors” that block Janus-associated kinase, or JAK, pathways, which are involved in the body’s immune response. JAK inhibitors are expected to compete for sales with biologic agents such as adalimumab, or Humira, and etanercept, or Enbrel, which revolutionized the treatment of RA and other types of inflammatory arthritis when they hit the marketplace almost 15 years ago. Unlike biologics, which are made from large and complex engineered proteins and taken by injection or infusion, JAK inhibitors are small-molecule medications that would be taken orally, once or twice a day.

Because they are not as complicated to manufacture, JAK inhibitors are expected to be less expensive than biologics, which can cost tens of thousands of dollars per year. Pfizer is not commenting on pricing.

For patients, JAK inhibitors will serve as an alternative to biologics – although they act in different ways. Tofacitinib essentially fights inflammation from inside the cell, while biologics block pro-inflammatory cytokines from outside the cell. There are several other small-molecule drugs like tofacitinib in testing phases, but this is the first to come before the FDA for approval.

“I think what’s notable about tofacitinib is it’s a new strategy for treating autoimmune diseases by blocking intracellular signaling,” explains John O’Shea, MD, scientific director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, or NIAMS, which is part of the National Institutes of Health, or NIH, in Bethesda, Md. Dr. O’Shea discovered one of the JAK pathways, for which he won the Arthritis Foundation's Howley Award in 2009. “What’s exciting to me about this is that we’ve gone from the discovery of a pathway about 20 years ago hopefully to new drugs that can help people with autoimmune diseases.”

Dr. O'Shea discloses he has had a collaborative research and development agreement with Pfizer since the 1990s and holds a patent with NIH for targeting JAKs.

If approved, the FDA will also have to decide on a dose – 5 mg and/or 10 mg – as well as the indication (the group of patients for which it will be approved).