Pipex Pharmaceuticals Announces Presentation of Phase I/II Clinical Trial Results of COPREXA (Oral Tetrathiomolybdate) for the Treatment of Refractory Idiopathic Pulmonary Fibrosis (IPF)
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Pipex Pharmaceuticals, Inc. (OTCBB: PPEX), a specialty pharmaceutical company developing innovative late-stage drug candidates for the treatment of neurologic and fibrotic diseases, announced today that the results of an open-label phase I/II clinical trial of COPREXA (oral tetrathiomolybdate) for the treatment of refractory Idiopathic Pulmonary Fibrosis (IPF) were presented at the American Thoracic Society (ATS) 2007 Annual Meeting in San Francisco by Kevin R. Flaherty, M.D., M.S., Associate Professor of Pulmonology at the University of Michigan. IPF is a fatal disorder with no FDA approved or effective therapy. This clinical trial was partially supported by a grant from the Coalition for Pulmonary Fibrosis, a non-profit organization.
Dr. Kevin Flaherty, the principal investigator of the clinical trial, stated, "Patients with IPF are in dire need for new potential effective therapies. COPREXA was easy to administer and well tolerated in a group of patients with progressive IPF, refractory to standard therapy. The pre-clinical work and patient tolerance of COPREXA makes us optimistic about this new treatment approach for IPF. We look forward to conducting a multi-center, double-blind, placebo controlled study of this agent."
COPREXA has completed two pivotal phase III trials for the treatment of neurologic Wilson's disease, an orphan genetic neurologic disease, and Pipex is preparing to file a New Drug Application (NDA) with the FDA for the indication of initially presenting neurologic Wilson's disease.
Clinical Trial Design
In a single-center, open-label, phase I/II clinical trial, 20 patients with IPF that had evidence of disease progression despite treatment with prednisone +/- cytotoxic therapy were treated for one (1) year with COPREXA (oral tetrathiomolybdate) 20mg capsules per oral twice a day with meals plus 20-40mg per oral at bedtime and adjusted as necessary to maintain a targeted serum ceruloplasmin range of 5-15mg/dl.
Patients were monitored for adverse events, change in pulmonary function as measured by percent predicted forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLco) and walk distance (six minute walk test room air). When pre-treatment FVC values were available, the course of pre-treatment FVC (slope) was compared to the post-treatment FVC (slope) at 6 and 12 months.
The baseline characteristics of the patients entered into the clinical trial were as follows:
Variable mean + sd -------- --------- Age (years) 69 +/- 7.1 Onset symptoms (years) 3.3 +/- 2.4 Smoker (yes/no/NA) 16/2/2 Pack*years 42.1 +/- 19.5 FVC (% predicted) 62 +/- 12 DLco (% predicted) 39 +/- 11 FVC >/- 55% predicted (yes/no) 15/5 DLco >/- 35% predicted (yes/no) 11/9 SaO2 < 88% during 6MWT (yes/no) 13/7
Clinical Trial Results
Patients responses at one (1) year were as follows:
Patients Patients Patients Stable Improved Progressed Forced Vital Capacity (FVC) 60% (12/20) 10% (2/20) 30% (6/20) Diffusing capacity of the lung for carbon monoxide (DLco) 75% (15/20) 5% (1/20) 20% (4/20)
Definitions: Stable = Change in FVC less than 10%, DLCO less than 15%; Improved = Relative increase in FVC at least 10%, DLCO at least 15%; Progressed = Relative decrease in FVC at least 10%, DLCO at least 15%.
When pre-treatment forced vital capacity (FVC) values were available, the course of pre-treatment FVC (slope) was compared to the post-treatment FVC at 6 and 12 months. The change in the pre-treatment and post treatment FVC slopes demonstrated favorable trends in the rate of decline of FVC, at 6 months pre-treatment compared to 6 months post-treatment (p < 0.06) and at 12 months pre-treatment compared to 12 months post-treatment (p < 0.12).
High Resolution Computed Tomography (HRCT) was utilized in the study to reveal images of the lungs. A semi-quantitative approach to measuring interstitial inflammation (HRCT ground glass opacity pattern) and the extent of lung fibrosis (HRCT honeycomb) was utilized. The HRCT results were as follows:
High Resolution Baseline COPREXA Therapy P value Computed @ 12 month Tomography (HRCT) Ground Glass 1.31 + 0.81 1.03 + 0.67 0.02 Fibrosis 1.61 + 0.48 1.67 + 0.50 0.60
The results of the six minute distance walk test while on COPREXA at baseline and at (1) year for the patients that completed either or both of the walk tests were as follows:
Distance (feet) P value Baseline (n=15) 611 + 388 12 month (n=10) 735 + 461 Difference completed either (n=16) -123 + 477 0.32 completed both (n = 9) 86 + 426 0.56
The St. George's Respiratory Questionnaire (SGRQ) a standardized quantitative quality of life (QOL) measurement commonly utilized for lung disorder clinical trials showed a trend towards improvement, as follows:
Value P value Symptom 3.55 0.45 Impact -5.22 0.07 Activity -6.43 0.41 Total -4.41 0.17
During the study, patients were also monitored for adverse events. Dose-related nausea and cytopenias were the most common and expected side effects of COPREXA therapy. These side effects were reversible with drug holiday. Three patients did not complete the trial (patient preference n=2, anemia n=1), and 2 patients died during the trial, 1 of exacerbation/pneumonia at month 1 and 1 of IPF progression at month 6.
Overall, the results of this small pilot trial are believed to be encouraging given the requirement for progressive disease to enter the trial. These preliminary data give us enthusiasm for a larger placebo-controlled trial for patients with IPF to confirm that treatment with COPREXA will help stabilize the course of IPF. Later this year, Pipex plans to initiate a twelve month, multi-center, randomized, double-blind, placebo-controlled trial of COPREXA in IPF. A manuscript that further details the clinical trial and its results is in preparation and is expected to be submitted and published in a leading peer reviewed journal.
Preclinical Data of COPREXA in Animal Models in IPF
The scientific rationale for conducting this clinical trial was based on several published preclinical studies indicating that COPREXA favorably modulates the fibrotic response in numerous animal models including the well established bleomycin mouse model of pulmonary fibrosis. GJ Brewer et at, Inorg Biochem. 2004 Dec;98(12):2160-7 and GJ Brewer et al, J. Lab. Clin. Med. 2003, 141:210-6.
In these published studies, COPREXA demonstrated the ability to inhibit fibrosis in a number of well established animal models which is believed to be based upon its ability to sequester endogenous free copper and inhibit key fibrotric cytokines, including secreted protein acid rich in cysteine (SPARC), NF(Kappa)B, TGF-(Beta), FGF-2, IL-1, IL-6, IL-8 and connective tissue growth factor (CTGF).
In these preclinical models, COPREXA prevented inflammation and the fibrotic response of the lung to bleomycin. Bleomycin is an FDA approved agent which is known to cause lung fibrosis in humans. According to Dr. George Brewer, Professor Emeritus of Human Genetics at the University of Michigan, inventor of this utility for COPREXA and co-author of the clinical trial, "An effective treatment for IPF is a key medical goal since the outcome of patients is grim and the prevalence of this disease in the population is increasing. Our observations that COPREXA significantly inhibited the fibrotic pathway has led us toward a new potential paradigm for the treatment of this deadly disease. We are very excited about the potential of bringing this new potential oral therapy to the 124,000 American patients afflicted with IPF."
Acknowledgements
Kevin R Flaherty, M.D., M.S. acknowledged the assistance of the following collaborators, Douglas A. Arenberg, M.D., Eric S. White, M.D., Victor Thannickal, M.D., Adin-Cristian Andrei, Ph.D.**, Susan Murray, Sc.D.**, Thomas V. Colby, M.D.*, William D. Travis, M.D.+, Ella A. Kazerooni, M.D., Barry H. Gross, M.D, Robert Paine III, M.D., Galen B. Toews, M.D., George J. Brewer, M.D. and Fernando J. Martinez, M.D., M.S. of the University of Michigan Health System, Ann Arbor, MI; Mayo Clinic, Scottsdale, AZ (*), Memorial Sloan Kettering, New York, NY (+) and the Department of Biostatistics, University of Michigan School of Public Health (**).
About IPF
IPF is a fatal respiratory disease characterized by progressive loss of lung function due to extensive fibrosis of lung tissues that are essential for respiration and life. According to the Pulmonary Fibrosis Foundation and Coalition for Pulmonary Fibrosis, IPF affects an estimated 124,000 patients in the U.S., including 48,000 new patients per year, and results in approximately 30,000 deaths in the U.S. annually. This represents more deaths annually than deaths from either breast or prostate cancer.
Currently, there are no FDA approved therapies for IPF. Standard of care for IPF patients are high dose corticosteroids and immunosuppresants which have numerous side effects that increase patient morbidity.
About COPREXA
COPREXA is an oral, small-molecule, anti-copper agent that is highly specific for the reduction of free copper in serum, the most toxic form of copper in the body, and is thus ideally suited for the treatment of central nervous system (CNS) diseases in which abnormal serum and CNS copper homeostasis are implicated. COPREXA has completed pivotal clinical trials for the treatment of neurologic Wilson's disease for which we are planning to file a New Drug Application (NDA). We are also developing COPREXA for fibrotic disorders based upon the rationale that the fibrotic disease process is dependent upon the availability of free copper in the body. COPREXA has demonstrated the ability to inhibit fibrosis in a number of well established animal models through the sequestration of available copper and inhibition of key fibrotric cytokines, including secreted protein acid rich in cysteine (SPARC), NF(Kappa)B, TGF-(Beta), FGF-2, IL-1, IL-6, IL-8, and connective tissue growth factor (CTGF).
As such, COPREXA is also in a phase II clinical trial for the treatment of primary biliary cirrhosis (PBC), a fibrotic disease of the hepatic system.
About Pipex Pharmaceuticals, Inc.
Pipex Pharmaceuticals, Inc. ("Pipex") is a specialty pharmaceutical company that is developing proprietary, late-stage drug candidates for the treatment of neurologic and fibrotic diseases Pipex's strategy is to exclusively in-license proprietary, clinical-stage drug candidates and complete the further clinical testing, manufacturing and regulatory requirements sufficient to seek marketing authorizations via the filing of New Drug Applications (NDAs) with the FDA in the U.S. and Marketing Application Authorizations (MAAs) with the European Medicines Evaluation Agency (EMEA). For further information, please visit, www.pipexpharma.com.
This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, that reflect Pipex Pharmaceuticals, Inc. and Pipex Therapeutics, Inc. ("we" or "our") current expectations about its future results, performance, prospects and opportunities, including statements regarding the potential use of COPREXA(TM) for the treatment of Idiopathic Pulmonary Fibrosis, Wilson's disease, inflammatory and fibrotic diseases, as well as its the prospects for regulatory filings in the treatment of neurologic Wilson's disease. Where possible, the Company has tried to identify these forward-looking statements by using words such as "anticipates," "believes," "intends," or similar expressions. These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements. We cannot assure you that we will be able to successfully develop or commercialize products based on our technologies, including COPREXA(TM), TRIMESTA(TM), SOLOVAX(TM), EFFIRMA(TM) or Anti-CD4 802-2, particularly in light of the significant uncertainty inherent in developing, manufacturing and conducting preclinical and clinical trials of new pharmaceuticals, and obtaining regulatory approvals, that our technologies will prove to be safe and effective, that our cash expenditures will not exceed projected levels, that we will be able to obtain future financing or funds when needed, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that we will be able to successfully obtain any further grants and awards, maintain our existing grants which are subject to performance, that we will be able to patent, register or protect our technology from challenge and products from competition or maintain or expand our license agreements with our current licensors, or that our business strategy will be successful. All forward-looking statements made in this press release are made as of the date hereof, and the Company assumes no obligation to update the forward-looking statements included in this news release whether as a result of new information, future events, or otherwise. The forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those set forth or implied by any forward-looking statements.
For Further Information Contact: Steve H. Kanzer, CPA, Esq. Chairman and Chief Executive Officer (734) 332-7800 or Thomas Redington (Investor Relations) Redington, Inc. Tel: (203) 222-7399
SOURCE: Pipex Pharmaceuticals Inc.
