Pfizer's first-in-class JAK inhibitor pricey for rheumatoid arthritis market

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Author: Ken Garber
Date: Jan. 2013
From: Nature Biotechnology(Vol. 31, Issue 1)
Publisher: Nature Publishing Group
Document Type: Article
Length: 1,419 words
Lexile Measure: 1380L

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On November 6, two weeks ahead of dead-line, the US Food and Drug Administration (FDA) approved the first Janus kinase (JAK) inhibitor for rheumatoid arthritis. With the approval, New York based Pfizer's small-molecule Xeljanz (tofacitinib) is poised to test the multibillion dollar rheumatoid arthritis market, currently dominated by tumor necrosis factor alpha (TNF) inhibitors. In clinical trials, Xeljanz showed similar efficacy to TNF inhibitors and a comparable safety profile. As a pill, it has obvious appeal and the indication is fairly generous--the drug is approved for moderate to severe rheumatoid arthritis in patients who fail methotrexate treatment. But Xeljanz is unlikely to quickly erode existing market share for the nine approved rheumatoid arthritis biologics. An unexpectedly high price point and uncertainty over long-term toxicity suggest Xeljanz's market entry will be gradual.

JAK inhibition is a completely novel mechanism in rheumatoid arthritis. Xeljanz's approval is the culmination of basic science research that began in the early 1990s at the US National Institutes of Health (NIH), identifying JAKs as the kinases that enable types I and II cytokine receptors to signal. NIH researchers also revealed the immunosuppressive effects of JAK inhibition and encouraged Pfizer to launch its JAK kinase inhibitor program, which originally focused on organ transplantation. Pfizer designed Xeljanz (tofacitinib) to be a JAK3 inhibitor--although the drug inhibits all three JAKs to some extent (Nat. Biotechnol. 29, 467-468, 2011). Rheumatoid arthritis is Xeljanz's first indication, but late-stage trials for psoriasis and ulcerative colitis are ongoing.

Leslie Crofford, a rheumatologist at the University of Kentucky in Lexington, welcomes the addition of Xeljanz to the available therapies, which already include a plethora of effective TNF inhibitors and other biologics. "The more options, the better," she says. With current treatments, the proportion of patients who achieve a 70% reduction in the number of tender and swollen joints and other parameters (ACR70 response), basically disease remission, is 20-30%, says Crofford. Though many others control their disease well using existing biologics, about half end up switching within five years of starting, according to Eric Matteson, chair of rheumatology at the Mayo Clinic in Rochester, Minnesota. "The opportunity to use drugs...

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Gale Document Number: GALE|A316204112