Vertex Moves to Re-allocate Resources from VX-745 in p38 MAP Kinase Program to Accelerate Development of Second Generation Drug Candidates VX-702 and VX-850
CAMBRIDGE, Mass., Sept. 24 /PRNewswire/ -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX - news) announced today that the Company has made a commercial decision to re-allocate its development resources in its small molecule p38 MAP kinase inhibitor program targeting inflammatory disease. As part of this decision, Vertex is suspending current clinical development of its lead orally active p38 MAP kinase inhibitor VX-745. Concurrently, in an analysis of clinical data of VX-745 in the treatment of rheumatoid arthritis, Vertex has obtained ``proof of principle`` correlating inhibition of p38 MAP kinase with a significant anti-inflammatory effect. Based on this encouraging finding, Vertex is accelerating the development of its second generation oral p38 MAP kinase inhibitors VX-702 and VX-850. Vertex intends to initiate clinical studies with one or both of these second generation p38 MAP kinase inhibitors in the first half of 2002.
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The decision to suspend clinical development of VX-745 is based directly on adverse effect findings within nonclinical (animal) tests. In one of two animal species receiving high-dose VX-745 exposure, adverse effect findings within the central nervous system (CNS) were noted. The tests were conducted as part of standard nonclinical safety evaluations in support of long term human clinical studies. The blood levels of VX-745 that were associated with neurological effects in animals were approximately ten times higher than the blood levels obtained in human clinical trials to date. Nonclinical tests have indicated that VX-745 crosses from the blood into the CNS. No neurological side effects associated with the drug have been observed in clinical trials of VX-745 to date.
``Vertex`s strategy focuses on the discovery of multiple drug candidates, representing distinct chemical classes, for each novel protein target,`` said Dr. Joshua Boger, Chairman and CEO of Vertex. ``In our p38 MAP kinase program, we have two second generation drug candidates which do not cross from the bloodstream into the CNS, VX-702 and VX-850, one or both of which we can move into clinical development quite rapidly. Based on the clinical data we have gathered to date, Vertex remains committed to maintaining our leadership position in exploring the clinical and commercial opportunity of p38 MAP kinase inhibitors.``
Vertex intends to present the clinical data from the Phase II clinical study in rheumatoid arthritis in a peer-reviewed forum in 2002. In January 2001, Vertex began a 12-week, randomized, placebo-controlled clinical trial of VX-745 in rheumatoid arthritis patients. The objective of the study was to assess the safety, pharmacokinetics and clinical activity of VX-745 at two dose levels. Vertex has completed the treatment and preliminary evaluation of the first (lower dose) cohort of patients in the study. In this study, VX-745 was generally well-tolerated and no CNS adverse events were observed. Vertex also obtained confirmatory evidence that inhibition of the p38 MAP kinase mechanism with an orally active drug can produce a significant clinical effect, based on the study`s primary endpoint of ACR 20 response in patients dosed with VX-745 compared to placebo. ACR 20 is a standard measure of response to treatment in rheumatoid arthritis patients, and represents improvement in a variety of clinically relevant signs and symptoms of disease.
Based on the CNS effects observed in ongoing nonclinical (animal) toxicology testing, Vertex voluntarily made the decision to not proceed with enrollment of patients in the higher-dose cohort of the rheumatoid arthritis study and to suspend the trial. In addition, an ongoing trial of VX-745 in myelodysplastic syndrome has also been stopped. The Company does not anticipate any material financial effect in 2001 related to the change in focus for the p38 MAP kinase program. The potential for further clinical development of VX-745 will be evaluated following a full analysis of clinical and nonclinical data, as well as possible additional nonclinical tests.
``Based on the `proof of principle` clinical and safety data we have generated to date, we remain highly confident that we can develop and commercialize p38 MAP kinase inhibitors that will provide a major clinical advance in inflammatory diseases such as rheumatoid arthritis,`` said John Alam, M.D., Senior Vice President of Drug Evaluation and Approval at Vertex. ``Although clinical data provided support for continued development of VX-745, at this time we believe the prudent action is to refocus our development efforts on second generation p38 inhibitors. We intend to initiate clinical studies with our second generation p38 inhibitors in the first half of 2002.``
``Vertex is well-positioned as a leader in small molecule drug discovery and development,`` said Dr. Boger. ``Vertex has one drug on the market, more than ten drug candidates in development addressing multiple areas of significant unmet medical need, a strong cash position and more than 25 collaborations with pharmaceutical and biotechnology companies. We look forward to continued advancement of our pipeline and the addition of new drug candidates into development in the months ahead.``
About VX-702, VX-850 and P38 MAP Kinase inhibitors
Vertex is accelerating development of its two second generation p38 MAP kinase inhibitor drug candidates, VX-702 and VX-850. These drug candidates, which were brought forward into development by Vertex in 2000, are oral, potent, selective and chemically distinct from VX-745. These drug candidates also possess unique properties that distinguish them from VX-745 and from each other. Vertex`s preclinical studies of these compounds demonstrate that VX-702 and VX-850 do not cross the blood-brain barrier to penetrate into CNS tissues. Vertex anticipates initiating clinical studies with one or both of these drug candidates in the first half of 2002. In addition, both compounds have a favorable preclinical pharmacokinetic profile for development in rheumatoid arthritis, with demonstrated bioavailability upon oral administration, no penetration into the CNS, and encouraging formulation characteristics.
Vertex has led the discovery and development of p38 MAP kinase inhibitors, which have the potential to be a powerful new class of oral anti-inflammatory medicines that reduce cytokine activity through a novel mechanism of action. P38 MAP kinase regulates the production of two proinflammatory cytokines, TNF alpha and IL-1, which have been implicated in a range of inflammatory diseases. In addition to rheumatoid arthritis, p38 MAP kinase inhibitors may play a future role in the treatment of other inflammatory diseases as well as heart failure and other diseases. Vertex holds development and commercial rights in the United States and Europe for its p38 MAP kinase inhibitors. Kissei Pharmaceutical Co., Ltd. holds development and commercial rights in Japan and certain Asian countries for VX-745 and VX-702, and holds an option to develop and commercialize VX-850.
Vertex Pharmaceuticals Incorporated is a global biotechnology company. Vertex seeks to discover, develop, and commercialize major pharmaceutical products independently and with partners. Chemogenomics, Vertex`s proprietary, systematic, genomics-based platform, is designed to accelerate the discovery of new drugs and to expand intellectual property coverage of drug candidate compounds and classes of related compounds. Vertex`s first approved product is Agenerase® (amprenavir), an HIV protease inhibitor, which Vertex co-promotes with GlaxoSmithKline. Vertex has more than ten drug candidates in clinical and preclinical development to treat viral diseases, inflammation, cancer, autoimmune diseases and neurological disorders.
This press release may contain ``forward-looking`` statements, including statements that Vertex anticipates initiating clinical studies with one or both of VX-702 and VX-850 in the first half of 2002, that Vertex is confident that it can develop and commercialize p38 MAP kinase inhibitors that will provide a major clinical advance in inflammatory diseases and that Vertex`s pipeline will continue to advance in the months ahead. While Vertex`s management makes its best efforts to be accurate in making forward-looking statements, such statements are subject to risks and uncertainties that could cause actual results to vary materially. These risks and uncertainties include, among other things, that clinical trials may not result in a marketable product, that Vertex will be unable to secure regulatory approval of, or successfully market, its drug candidates, that Vertex may be further unable to identify, develop, and achieve commercial success for new products and technologies, that Vertex is dependent upon pharmaceutical and biotechnology collaborations, and the levels and timing of payments under Vertex`s collaborative agreements, that Vertex may be unable to obtain new corporate collaborations, maintain existing collaborations and acquire new technologies on satisfactory terms, if at all, that Vertex may be unable to adequately protect its proprietary technologies against patent-infringement claims, and risk of new, changing, and competitive technologies and regulations in the U.S. and internationally. Vertex disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.
Agenerase® is a trademark of the GlaxoSmithKline group of companies.
Vertex`s press releases are available at www.vrtx.com, or by fax-on-demand at (800) 758-5804 - Code: 938395
SOURCE: Vertex Pharmaceuticals Incorporated