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AbbVie Announces the Launch of Robust Phase 3 Clinical Trial Program Evaluating ABT-494, an Investigational Selective JAK1 Inhibitor, for the Treatment of Rheumatoid Arthritis
 
 
  Jak inhibitors exhibit a novel mechanism of HIV inhibition in primary human and rhesus macaque macrophages and lymphocytes: 'functional cure?'......
http://www.natap.org/2012/ResisWksp/ResisWksp_16.htm
 
Galapagos and Gilead Announce Global Partnership to Develop Filgotinib for the Treatment of Rheumatoid Arthritis and Other Inflammatory Diseases/HIV Cure application.....http://www.natap.org/2016/HIV/010416_01.htm

 
Abstract 37 by RF Schinazi and colleagues was on the topic of a novel series of inhibitors of HIV replication called Jak inhibitors. These compounds are able to interfere with the Jak-STAT pathway in activated lymphocytes and macrophages in the aftermath of HIV infection. Activation and reactivation of cells was performed using monoclonal antibodies against CD3 and/or CD28 and activation was monitored by flow cytometry. The Jak-STAT pathway is routinely stimulated in HIV-infected cells and can therefore be perceived as a logical target for drug development. Now, in this proof of concept study, it has been shown that two lead compounds termed Tofacitinib and Jakafi demonstrated excellent inhibition of HIV replication at concentrations ranging between 0.02-0.3 ÁM in cultured human lymphocytes and macrophages as well as against replication of a SHIV in lymphocytes and macrophages obtained from rhesus macaques. Moreover, these compounds were not toxic and the selectivity index for each of these compounds was high. This is the first demonstration that targeted blockage of the Jak-STAT pathway might be an effective way of interfering with HIV replication in both macrophages and lymphocytes. Moreover, the data suggest that these compounds might interfere with the ability of HIV to achieve latency in a variety of target cell types and that they were active against all of a variety of forms of drug-resistant HIV-1 that were tested. In addition, activity was demonstrated in regard to latently infected cells that were re-activated so as to become overt producers of HIV. The field will now await further studies on some of the molecules in this series, at least some of which are already approved by the Food and Drug Administration in regard to other disease indications, such as rheumatoid arthritis and myeleofibrosis.
 
http://www.natap.org/2012/ResisWksp/ResisWksp_13.htm
 
Aging - New drugs - (01/08/16)
 
......the small-molecule compound ABT263, which is a specific inhibitor of the apoptosis genes BCL2 and BCL2L1 (encoding BCL-2 and BCL-xL, respectively), selectively induced apoptosis of senescent cells in culture in a cell type- and species-independent (mouse as well as human).......Senescent cells, now identifiable by a validated set of independent markers, accumulate in tissues during aging or upon tissue damage induced by stimuli such as irradiation1. Multiple distinct roles for senescent cells in tissues have been suggested. However, it is now commonly accepted that senescent cells contribute to tissue attrition and to aging-associated initiation of cancer, in part via the factors they secrete, collectively known as the senescence-associated secretory phenotype (SASP).
 
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AbbVie Announces the Launch of Robust Phase 3 Clinical Trial Program Evaluating ABT-494, an Investigational Selective JAK1 Inhibitor, for the Treatment of Rheumatoid Arthritis
 
- After positive results in the BALANCE Phase 2 trials, ABT-494, a second generation(1) oral selective JAK1 inhibitor, has moved into Phase 3 clinical trials for rheumatoid arthritis, starting in December 2015
 
- Five Phase 3 trials will evaluate over 4,000 patients with moderate to severe rheumatoid arthritis
 
Jan 8, 2016
 
NORTH CHICAGO, Ill., Jan. 8, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced the start of a large Phase 3 clinical trial program to study the use of ABT-494, an investigational, once-daily, oral selective JAK1 inhibitor for the treatment of rheumatoid arthritis (RA). This program will include adult patients with inadequate responses (IR) to conventional or biologic disease-modifying antirheumatic drugs (DMARDs), as well as methotrexate-naive patients.
 
"We continue to leverage our expertise in rheumatology and immunology to address the unmet needs of patients living with immune-mediated diseases, including those that fail to respond to the current standard of care," said Scott Brun, M.D., vice president, pharmaceutical development, AbbVie. "We are optimistic that our robust Phase 3 clinical trial program, which dosed the first patient in December, will help us further understand the therapeutic potential of ABT-494 across multiple patient populations and achieve our goal of providing patients with best-in-class treatment options."
 
Data from the Phase 2 ABT-494 clinical trials, BALANCE-I and BALANCE-2, announced in September 2015, demonstrated the efficacy of ABT-494 across 6, 12 and 18 mg doses twice-daily, and 24 mg once-daily in RA patients with an inadequate response to prior anti-tumor necrosis factor (TNF-IR) or methotrexate (MTX-IR) treatment.
 
The first two trials out of the five Phase 3 ABT-494 clinical trials have opened for enrollment in the United States. One study will evaluate ABT-494 in combination with MTX in adult patients with moderate to severely active RA who have had an inadequate response to prior treatment with MTX, and will include HUMIRA® (adalimumab) as an active comparator. The second study will include patients who have had an inadequate response or intolerance to conventional synthetic DMARDs. These studies will include assessments of safety and tolerability, as well as key measures of efficacy including ACR responses and levels of disease activity.
 
The other three Phase 3 clinical trials will begin enrollment in early 2016 and will include patients with an inadequate response to biologics and patients who are MTX-naive.
 
About the SELECT-COMPARE Clinical Trial SELECT-COMPARE is a double-blind, placebo-controlled and active controlled Phase 3 study designed to evaluate the safety and efficacy of ABT-494 in combination with MTX in adult patients with moderate to severely active RA who have had an inadequate response to prior treatment with MTX. The trial duration is 48 weeks with a target enrollment of 1,500 patients.
 
About the SELECT-NEXT Clinical Trial SELECT-NEXT is a double-blind, placebo-controlled, Phase 3 study designed to evaluate the safety and efficacy of two doses of ABT-494, 15 mg once-daily (QD) and 30 mg QD, in combination with conventional synthetic DMARDS. The study will enroll approximately 600 adult patients with moderate to severely active RA who have had an inadequate response or intolerance to conventional synthetic DMARDs.
 
For additional information on this clinical trial program, please visit www.clinicaltrials.gov.
 
About ABT-494 Pioneered by AbbVie, ABT-494 is an investigational, second generation, oral agent that selectively inhibits JAK1, which plays an important role in the inflammatory process of RA. A Phase 2 trial of ABT-494 for the treatment of Crohn's disease is also ongoing.
 
About AbbVie AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page. Forward-Looking Statements Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.
 
Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
 
References
 
1. Voss, Jeffrey, Graff, Candace, Schwartz, Annette, Hyland, Deborah, Argiriadi, Maria, Camp, Heidi, et al; Pharmacodynamics Of a Novel Jak1 Selective Inhibitor In Rat Arthritis and Anemia Models and In Healthy Human Subjects.
[abstract]. Arthritis Rheum 2013;65 Suppl 10 :2374. DOI:
10.1002/art.2013.65.issue-s10
 
SOURCE AbbVie
 
For further information: Media: Raquel Powers, (847) 935-6563; Investors: Liz Shea, (847) 935-2211

 
 
 
 
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