Pfizer Announces Top-Line Results of Third Phase 3 Clinical Trial of Tofacitinib (CP-690,550)

PfizerPfizer Inc. announced top-line results from the ORAL Scan Phase 3 study (A3921044) of tofacitinib (development code: CP-690,550), formerly known as tasocitinib, an investigational, novel, oral JAK inhibitor. ORAL Scan is an ongoing two-year study in patients with moderate-to-severe active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX) and were randomized to receive tofacitinib 5 or 10 mg BID or placebo added to background MTX. The data reported are from a planned analysis at one year.

The ORAL Scan study met all primary endpoints at the 10 mg BID dose, showing statistically significant changes versus placebo in reducing signs and symptoms of RA, as measured by ACR20 response rates at six months; in reducing the progression of structural damage, as measured by change from baseline in modified Total Sharp Score (mTSS) at six months; in improving physical function, as measured by mean change in HAQ DI at three months; and in reaching DAS28-4(ESR) <2.6 at six months.

For the 5 mg BID dose, the study demonstrated statistically significant improvements versus placebo in ACR20 response rates at six months, but the difference from placebo in mTSS did not reach statistical significance at six months. Due to the pre-specified step-down statistical procedure, no further testing was performed on HAQ DI and DAS28-4(ESR) <2.6 for the 5 mg BID dose.

No new safety signals emerged in the ORAL Scan study. The efficacy and safety profile of tofacitinib in this study remains consistent with that seen previously in the clinical program. A full analysis of the ORAL Scan efficacy and safety data will be submitted to a future scientific meeting.

About ORAL Scan
ORAL Scan is an ongoing two-year study that randomized 800 patients with moderate-to-severe active RA who had an inadequate response to MTX to receive tofacitinib 5 or 10 mg BID or placebo added to background MTX. At the three month visit, non-responding placebo-assigned patients were advanced in a blinded fashion to a predetermined treatment of tofacitinib, 5 or 10 mg BID, for the remainder of the study. At the end of six months, all placebo-assigned patients were advanced to their predetermined tofacitinib treatment assignment in a blinded fashion for the remainder of the study. The two year data from this study are expected in 2012.

About Rheumatoid Arthritis
Rheumatoid arthritis is a chronic inflammatory autoimmune disease that typically affects the hands and feet, although any joint lined by a synovial membrane may be affected. RA affects approximately 1.3 million people in the U.S.(1) and one percent of the adult population worldwide.(2)

About Tofacitinib
Tofacitinib is a novel, oral Janus kinase (JAK) inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy for RA. More than 4,000 RA patients have been treated with tofacitinib in clinical trials to date. Unlike current therapies for RA, which are directed at extracellular targets such as pro-inflammatory cytokines, tofacitinib takes a novel approach, targeting the intracellular signaling pathways that operate as hubs in the inflammatory cytokine network.

In addition to ORAL Scan (A3921044), the ORAL Trials clinical program includes the following pivotal Phase 3 studies of tofacitinib in RA:

  • ORAL Solo (A3921045): 6-month study in inadequate responders to a disease modifying anti-rheumatic drug (DMARD), traditional or biologic, receiving tofacitinib monotherapy, evaluating signs and symptoms and physical function.
  • ORAL Sync (A3921046): 12-month study in inadequate responders to a DMARD (traditional or biologic) receiving tofacitinib and background traditional DMARD(s), evaluating signs and symptoms and physical function.
  • ORAL Standard (A3921064): 12-month study in inadequate responders to MTX receiving tofacitinib and background MTX, with active comparator of adalimumab and background MTX, evaluating signs and symptoms and physical function.
  • ORAL Step (A3921032): 6-month study in inadequate responders to TNF-inhibiting therapy receiving tofacitinib and background MTX, evaluating signs and symptoms and physical function.

In addition, there is an ongoing Phase 3 study that will not be a part of the initial registration:

  • ORAL Start (A3921069): 24-month study in MTX-naïve patients receiving tofacitinib monotherapy or MTX, including a structural endpoint in addition to evaluating signs and symptoms and physical function.

Pfizer is also studying orally administered tofacitinib in psoriasis, inflammatory bowel disease (Crohn’s disease and ulcerative colitis) and renal transplant, and topical tofacitinib in both psoriasis and dry eye disease.

Pfizer Inc.: Working together for a healthier world™
At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Our diversified global health care portfolio includes human and animal biologic and small molecule medicines and vaccines, as well as nutritional products and many of the world's best-known consumer products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as the world's leading biopharmaceutical company, we also collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us.

1. Arthritis Today. “What is Rheumatoid Arthritis.” Accessed 24 February 2011. Available at: http://www.arthritistoday.org/conditions/rheumatoid-arthritis/all-about-ra/what-is-ra.php.
2. Rubbert-Roth A, Finckh A. Treatment options in patients with rheumatoid arthritis failing initial TNF inhibitor therapy: a critical review. Arthritis Res Ther. 2009; 11(Suppl 1): S1.Published online 2009 April 6. doi: 10.1186/ar2662.

Most Popular Now

Delivering insulin in a pill

Given the choice of taking a pill or injecting oneself with a needle, most of us would opt to regulate a chronic health condition by swallowing a pill. But for millions o...

Can aspirin treat Alzheimer's?

A regimen of low-dose aspirin potentially may reduce plaques in the brain, which will reduce Alzheimer's disease pathology and protect memory, according to neurological r...

FDA approves first drug comprised of an active ing…

The U.S. Food and Drug Administration today approved Epidiolex (cannabidiol) [CBD] oral solution for the treatment of seizures associated with two rare and severe forms o...

Researchers develop a new method for turning skin …

Our bodies consist of many different kinds of cells, each with their own role. The Japanese scientist Shinya Yamanaka had made earlier the discovery, earning the Nobel Pr...

Some existing anti-cancer drugs may act in part by…

Bolstering the notion that RNA should be considered an important drug-discovery target, scientists at Scripps Research have found that several existing, FDA-approved anti...

Poliovirus therapy for recurrent glioblastoma has …

A genetically modified poliovirus therapy developed at Duke Cancer Institute shows significantly improved long-term survival for patients with recurrent glioblastoma, wit...

Human clinical trial reveals verapamil as an effec…

Researchers at the University of Alabama at Birmingham Comprehensive Diabetes Center have discovered a safe and effective novel therapy to reduce insulin requirements and...

Novartis Clear about Psoriasis survey data highlig…

Novartis announced today the publication of global Clear about Psoriasis survey data in the Journal of the European Academy of Dermatology and Venereology[1]. The publica...

New small molecules pave the way for treating auto…

The innate immune system is the first line of defense, with cells that quickly identify "foreign" motifs from viruses and bacteria and mount up a counterattack to elimina...

How targeting metabolism can defeat cancer stem ce…

Researchers are the University of Michigan Rogel Cancer are unraveling a crucial thread that explains why cancer so often becomes resistant to treatment. In a breakthroug...

Amgen and MBC Biolabs announce winners of the Amge…

Amgen (NASDAQ:AMGN) and MBC BioLabs (formerly QB3@953) announced that Delve Therapeutics and Mitokinin have won the Amgen Golden Ticket at MBC BioLabs. Each company recei...

FDA warns of imposters sending consumers fake warn…

The U.S. Food and Drug Administration is warning consumers about criminals forging FDA warning letters to target individuals who tried to purchase medicines online or ove...