Pfizer Inc. (NYSE:PFE) announced today detailed results from OPT Compare (A3921080), a Phase 3 study of tofacitinib, the first in a new class of treatment, oral Janus kinase (JAK) inhibitors, the safety and efficacy of which are being investigated for the treatment of adults with moderate-to-severe chronic plaque psoriasis. Top-line results from OPT Compare were previously announced in October 2013. This is the first of five studies from the Phase 3 Oral treatment Psoriasis Trial (OPT) Program, one of the largest global clinical trial programs in moderate-to-severe chronic plaque psoriasis to date. The results of OPT Compare showed that in a step-down procedure design, tofacitinib 10 mg twice daily (BID) was non-inferior to high-dose ENBREL ® (etanercept) 50 mg twice weekly (BIW), and tofacitinib 5 mg twice daily did not meet the non-inferiority criteria compared to high-dose ENBREL. No new safety signals for tofacitinib were observed in the OPT Compare study. Detailed results of this study are being presented as an oral presentation during the Latest in Dermatology Research Symposium at the 72nd American Academy of Dermatology (AAD) Annual Meeting held in Denver, at 9:45 a.m. MDT today. “We are pleased to present the detailed results of OPT Compare, the first Phase 3 trial showing non-inferiority of an oral small molecule, tofacitinib, versus an injected biologic agent, ENBREL, in psoriasis. The results demonstrated that tofacitinib 10 mg twice daily had similar efficacy to high-dose ENBREL 50 mg twice weekly,” said lead author Hervé Bachelez, M.D., Ph.D., Sorbonne Paris Cité Université Paris Diderot, Department of Dermatology, APHP Hôpital Saint-Louis, Paris, France. OPT Compare is a 12-week, non-inferiority study comparing the efficacy and safety of tofacitinib 5 mg and 10 mg BID to high-dose ENBREL 50 mg BIW, the approved starting dose for ENBREL for the first 12 weeks, and placebo for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis. The results of the study showed that tofacitinib 10 mg BID was non-inferior to high-dose ENBREL 50 mg BIW as measured by Psoriasis Area and Severity Index (PASI) 75 response and Physician’s Global Assessment (PGA) response. The proportion of patients that achieved a PASI75 response at week 12 was: tofacitinib 10 mg BID: 63.6 percent; ENBREL 50 mg BIW: 58.8 percent; tofacitinib 5 mg BID: 39.5 percent; placebo: 5.6 percent. The proportion of patients that achieved “clear” or “almost clear” in PGA at week 12 were: tofacitinib 10 mg BID: 68.2 percent; ENBREL 50 mg BIW: 66.3 percent; tofacitinib 5 mg BID: 47.1 percent; placebo: 15.0 percent. Tofacitinib 5 mg BID did not meet the non-inferiority criterion of 15 percent difference compared to high-dose ENBREL as measured by PASI75.
The efficacy and safety profile of tofacitinib in this study was expected based on what was seen in the Phase 2 clinical trial and dose modeling. Rates of selected safety events of special interest in the study patient population, including serious infections, herpes zoster, non-melanoma skin cancer and cardiovascular events, were below 1 percent and similar for all active treatment groups (both tofacitinib arms and the ENBREL arm). The most frequent adverse events across active treatment groups were infections (most commonly nasopharyngitis and upper respiratory tract infections). Injection site reactions were more frequent among patients receiving active ENBREL treatment compared with the tofacitinib and placebo arms, whereas increases in cholesterol and creatine phosphokinase were more common in tofacitinib recipients.The detailed OPT Compare study results mark the completion of the first Phase 3 trial for tofacitinib in psoriasis. Top-line results for the second completed study, OPT Retreatment (A3921111), were previously announced in October 2013, and detailed results will be presented at a future scientific meeting. Top-line results from two of the three remaining trials in the Phase 3 Oral treatment Psoriasis Trial (OPT) Program, the OPT Pivotal 1 and OPT Pivotal 2 trials (A3921078 and A3921079), are anticipated in the second quarter of 2014, and these four studies, in addition to a long-term extension study, will form the planned psoriasis submission package to regulatory authorities. About OPT Compare (A3921080) OPT Compare was a Phase 3 randomized, double-blind, double-dummy, placebo-controlled 12-week non-inferiority study comparing the efficacy and safety of tofacitinib 5 mg and 10 mg BID to high-dose ENBREL (etanercept) 50 mg BIW and placebo (oral tablet and subcutaneous injection) for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis who had an inadequate response to, intolerance to, or contraindication to conventional systemic therapy. Patients that previously failed treatment with a tumor necrosis factor (TNF) inhibitor were excluded from this study. There were 1,106 patients enrolled in this study in 23 countries outside of the U.S. and Canada (three Latin American countries, three in Asia, 16 in Europe, and one in the Middle East).
About the OPT Clinical Trial ProgramThe Phase 3 OPT clinical trial program consists of five studies (including one open-label, long-term extension study) evaluating oral tofacitinib 5 mg and 10 mg BID in adults with moderate-to-severe chronic plaque psoriasis. It is a global, multi-study, comprehensive clinical development program that includes over 3,600 patients in 36 countries, and is one of the largest global clinical trial programs in moderate-to-severe chronic plaque psoriasis to date. The OPT Program is designed to specifically evaluate tofacitinib in moderate-to-severe chronic plaque psoriasis, and to support an independent assessment of the benefit: risk profile of tofacitinib in this particular patient population. In addition to OPT Compare, the OPT Program includes the following Phase 3 studies of tofacitinib in psoriasis:
- OPT Retreatment (A3921111): A phase 3 randomized, mixed-blind, three-period, parallel group, placebo-controlled study evaluating the efficacy and safety of the withdrawal and retreatment with tofacitinib 5 mg and 10 mg BID compared to placebo in adult patients with moderate-to-severe chronic plaque psoriasis.
- OPT Pivotal #1 (A3921078) and OPT Pivotal #2 (A3921079): Two Phase 3, 52-week, multi-site, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the safety and efficacy of tofacitinib 5 mg and 10 mg BID. The primary objectives of the studies are to compare the efficacy of tofacitinib to placebo for the reduction in severity of plaque psoriasis as measured by the proportion of patients achieving a PGA response of “clear” or “almost clear,” at week 16, and the proportion of patients achieving PASI75 relative to baseline at week 16, as well as to evaluate the safety and tolerability of tofacitinib over 52 weeks.
- OPT Extend (A3921061): An open-label long-term extension study evaluating the safety and tolerability of tofacitinib. Patients who participated in the Phase 2 trial or any of the other Phase 3 studies had the option, if eligible, to enroll in this study.
- It is not known if XELJANZ is safe and effective in people with Hepatitis B or C.
- XELJANZ is not for people with severe liver problems.
- It is not known if XELJANZ is safe and effective in children.
- XELJANZ can lower the ability of the immune system to fight infections. Some people have serious infections while taking XELJANZ, including tuberculosis (TB), and infections caused by bacteria, fungi, or viruses that can spread throughout the body. Some people have died from these infections. Healthcare providers should test patients for TB before starting XELJANZ, and monitor them closely for signs and symptoms of TB and other infections during treatment. People should not start taking XELJANZ if they have any kind of infection unless their healthcare provider tells them it is okay.
- XELJANZ may increase the risk of certain cancers by changing the way the immune system works. Malignancies were observed in clinical studies of XELJANZ.
- The risks and benefits of treatment should be considered prior to initiating XELJANZ in patients with chronic or recurrent infection; who have been exposed to tuberculosis; with a history of a serious or an opportunistic infection; who have resided or traveled in areas of endemic tuberculosis or endemic mycoses; or with underlying conditions that may predispose them to infection.
- Viral reactivation, including cases of herpes virus reactivation (e.g., herpes zoster), was observed in clinical studies with XELJANZ.
- Use of live vaccines should be avoided concurrently with XELJANZ. Update immunizations in agreement with current immunization guidelines prior to initiating XELJANZ therapy.
- Some people who have taken XELJANZ with certain other medicines to prevent kidney transplant rejection have had a problem with certain white blood cells growing out of control (Epstein Barr virus-associated post-transplant lymphoproliferative disorder).
- Some people taking XELJANZ get tears in their stomach or intestines. This happens most often in people who also take nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or methotrexate. Patients should tell their healthcare provider right away if they have fever and stomach-area pain that does not go away, or a change in bowel habits. XELJANZ should be used with caution in patients who may be at increased risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis).
- XELJANZ can cause changes in certain lab test results including low blood cell counts, increases in certain liver tests, and increases in cholesterol levels. Healthcare providers should do blood tests before starting patients on XELJANZ and while they are taking XELJANZ, to check for these side effects. Normal cholesterol levels are important to good heart health. Healthcare providers may stop XELJANZ treatment because of changes in blood cell counts or liver test results.
- Use of XELJANZ in patients with severe hepatic impairment is not recommended.
- Patients should tell their healthcare providers if they plan to become pregnant or are pregnant.
- It is not known if XELJANZ will harm an unborn baby. To monitor the outcomes of pregnant women exposed to XELJANZ, a registry has been established. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-311-8972.
- Patients should tell their healthcare providers if they plan to breastfeed or are breastfeeding. Patients and their healthcare provider should decide if they will take XELJANZ or breastfeed. They should not do both.
- In carriers of the hepatitis B or C virus (viruses that affect the liver), the virus may become active while using XELJANZ. Healthcare providers may do blood tests before and during treatment with XELJANZ.
- Common side effects include upper respiratory tract infections (common cold, sinus infections), headache, diarrhea, and nasal congestion, sore throat, and runny nose (nasopharyngitis).