SOURCE: Pipex Pharmaceuticals, Inc.

January 07, 2008 08:44 ET

Pipex Pharmaceuticals Initiates Phase II Clinical Trial of Anti-Copper COPREXA for Alzheimer's Disease

Newly Awarded Grant Funds Approximately 30% of Cost of Clinical Trial

150-Patient, Double-Blind, Randomized, Placebo-Controlled Trial Being Conducted by Leading Clinical Group Having Discovered and Extensively Studied Elevated Toxic Free Copper Levels in Alzheimer's Disease Patients

ANN ARBOR, MI--(Marketwire - January 7, 2008) - Pipex Pharmaceuticals, Inc. (AMEX: PP) ("Pipex"), a specialty pharmaceutical company developing innovative late-stage drug candidates for the treatment of neurologic and fibrotic diseases, announced that it has initiated a 150-patient, double-blind, placebo-controlled Phase II clinical trial of its lead anti-copper drug candidate, COPREXA (oral tetrathiomolybdate) for the treatment of Alzheimer's disease (AD). The clinical trial is being led by the leading clinical research group that first discovered and has most extensively studied and published findings of elevated toxic free copper levels in the serum of Alzheimer's patients. The Phase II clinical trial is also being partially supported by a grant from Italian Ministry of Health which is expected to fund approximately 30% of the cost of the trial.

Steve H. Kanzer, Chairman & Chief Executive Officer of Pipex commented, "Given the recent findings demonstrating COPREXA's ability to reduce insoluble amyloid beta plaques, a hallmark AD protein by 40% (p < 0.05) in Alzheimer's animal models, coupled with our findings of elevated free copper levels in AD patients, we believe that COPREXA represents an exciting new approach to treat what appears to represent an important underlying cause of Alzheimer's disease, namely, elevated free copper and CNS copper toxicosis in genetically susceptible elderly persons. Our scientific founder and inventor of COPREXA, George J. Brewer, M.D., was the first to identify elevated free copper as the cause of the neurodegeneration seen in neurologically-presenting Wilson's disease patients. He later specifically developed COPREXA for the purpose of specifically lowering free copper in neurologically presenting Wilson's disease patients, the results of which formed the basis of our New Drug Application of COPREXA for this indication, which we recently filed with the FDA in November. Professor Rossini, Dr. Squitti and their group were the first to identify a similar elevated pool of free copper in the serum in the socially important and growing disease that is Alzheimer's disease. We are both pleased and honored to collaborate with Prof. Rossini and Dr. Squitti, and are grateful to the Italian Ministry of Health for their grant support assisting the funding of this important Phase II clinical trial of COPREXA for Alzheimer's disease."

Prof. Paolo M. Rossini, Director of the Chair of Clinical Neurology in the University "Campus Biomedico" of Rome, Italy and Scientific Director of IRCCS of Brescia, Italy and of AFaR, Fatebenefratelli Association for Research, and principal investigator of this clinical trial said, "We are pleased to be working on this novel approach for the treatment of this devastating disease. Our group has published several clinical studies correlating the disease severity of AD patients to elevated levels of 'free' copper in serum. Currently, there are no adequate approved or disease modifying treatments for Alzheimer's and these results represent an important step forward for the 11 million patients suffering from Alzheimer's in the United States and Europe.

Dr Squitti, Head of the Laboratory of Biology of AFaR and of the Laboratory of Neurobiology in the University "Campus Biomedico" added, "'Free' copper may be intrinsically toxic to older persons due to its oxidative activity, small size and ability to cross the blood brain barrier and enter the central nervous system in an unregulated fashion, similar to elevated 'free' copper's effects in other diseases of copper metabolism, such as Wilson's disease. Our initial findings of elevated free copper in AD patients appear to be supported by the findings of others, some of whom have published earlier on copper/ceruloplasmin dyshomeostasis in AD, including Snaedal et al. 1998; Gonzales et al., 1999; Pajonk et al., 2005; and Kessler et al., 2006."

About the Phase II Clinical Trial of COPREXA in AD

The double blind, placebo-controlled, Phase II clinical trial is intended to enroll 150 mild to moderate AD patients who have an elevated levels of 'free' copper. Patients will be randomized on a 1:1 basis to receive either COPREXA plus an acetylcholineserase inhibitor or a placebo plus an acetylcholineserase inhibitor during the course of the study. The primary endpoint of the study is to evaluate cognition at 24 and 52 weeks utilizing the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) (Rosen et al., 1984; Mohs et al., 1996). The ADAS is a psychometric instrument designed to evaluate the severity of cognitive and noncognitive behavioral dysfunctions characteristic of people with AD. The cognitive portion (ADAS-Cog) assesses memory, language, and praxis functions. Secondary endpoints will evaluate changes in hippocampal volume measured by Magnetic Resonance Imaging (MRI) as well as other advanced neuroimaging markers of AD progression. The clinical trial is being conducted at four clinical trial sites throughout Italy.

Clinical Correlation of Copper and Alzheimer's Disease

Over the last several years, an increasing body of evidence points to dysfunctional copper homeostasis in the pathogenesis of AD. In 2006, a published epidemiological study conducted in 3718 patients over 65 years of age over a six year period, found that subjects that consumed a typical amount of a copper supplement (1.6mg of copper a day) when taken together with a high saturated and trans fat diet had an equivalent 19 years of cognitive decline over such six year period as compared to those who did not consume such copper (p < 0.001) (1).

In a separate clinical study conducted by Prof. Rossini and Dr. Squitti in 53 patients, correlated the levels of the highly reactive 'free' copper (also known as copper not bound to ceruloplasmin) pool in serum to disease severity in AD patients versus aged-matched control patients. These results demonstrated that the 'free' copper serum pool (p < 0.0001) was highly increased in AD patients (2).

In November, Pipex independently corroborated and reported the findings of elevated free copper by comparing serum samples from 40 autopsy-confirmed AD patients to serum samples from 12 age-matched controls. Utilizing Pipex's proprietary FreeBound investigational diagnostic device that for the first time permits the direct measurement of free copper in biological fluids, Pipex found statistically significant elevated serum free copper levels in the AD patients compared to age matched controls.

COPREXA's Potential Utility in Alzheimer's Disease

COPREXA's specificity and unique mechanism of action for potently lowering toxic levels of free copper in the CNS, combined with its history of success in completed pivotal clinical trials of neurologically-presenting Wilson's disease, may make it an excellent candidate to evaluate for the treatment of the elevated free copper levels and copper containing plaques and tangles that characterize AD. The current Phase II study is intended to evaluate the safety and efficacy of COPREXA in a limited number of patients. Should such study prove successful, the size, design and conduct of necessary Phase III clinical trials sufficient to demonstrate adequate safety and efficacy to support a potential NDA or Supplemental NDA of COPREXA for AD, are and would be subject to FDA and international regulatory authorizations and approval, if successful.

COPREXA's ability to specifically bind and lower toxic 'free' copper differentiates it from other non-specific metal chelating compounds previously and currently being investigated for neurodegenerative diseases. Such other chelators tend to liberate copper and thereby elevate free copper levels and the bioavailability of free copper to the CNS as well as interact non-specifically with other metals.

Market Opportunity of COPREXA for Alzheimer's Disease

It is estimated that approximately 5 million Americans and 6 million Europeans suffer from AD. Risk factors for the disease include age and family history. Age is the most important risk factor for AD; the number of people with the disease doubles every five years beyond age 65. According to the Alzheimer's Association, the disease affects one in 10 persons over the age of 65, and 30% of those over 85 years old.

There is an urgent need for an effective treatment for the illness, caused in part by the rising health care, institutional, and social costs for the treatment and care of Alzheimer's sufferers. In May 2002, the National Institute on Aging (NIA) reported that the cost of care to family, caregivers and society in general was estimated to exceed $100 billion per year, up from $18 billion in 1996, ranking AD as the disease with the greatest economic cost to society. These costs are expected to rise sharply as the baby-boom generation ages and more people become at risk for the disease. As people live longer, their risk of developing AD increases.

The market for current AD treatments, all of which are palliative as opposed to disease modifying, account for over $3 billion in annual sales and is expected to grow to $5 billion by 2009.

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, an "Orphan" central nervous disease and Pipex filed an NDA with the FDA for COPREXA for this indication in November 2007.

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), NFKB, TGF-B, FGF-2, IL-1, IL-6, IL-8, and connective tissue growth factor (CTGF).

COPREXA has also completed a one-year Phase II clinical trial for the treatment of refractory Idiopathic Pulmonary Fibrosis (IPF), a deadly lung disease. Pending regulatory feedback, Pipex is planning to launch a Phase III clinical for the treatment of IPF with COPREXA.

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. In November 2007, Pipex filed an NDA for its lead drug candidate, COPREXA, for neurologically presenting Wilson's disease. 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.pipexinc.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 subsidiaries ("we" or "our") current expectations about its future results, performance, prospects and opportunities, including statements regarding the potential use of COPREXA for the treatment of Alzheimer's disease, Wilson's disease, Idiopathic Pulmonary Fibrosis, Huntington's disease, inflammatory and fibrotic diseases, as well as the prospects for our regulatory filings in the treatment of neurologic Wilson's disease, including the NDA filed for COPREXA with the FDA during November 2007 and that such NDA will be accepted for filing by the FDA and/or that the FDA will agree with our analysis of data supporting the safety, clinical efficacy, manufacturing, stability and other regulatory requirements necessary for COPREXA to be approved for use in neurologically-presenting Wilson's disease or that, even if it is approved for this initial indication, that we will be able to conduct and complete necessary initial and registration clinical trials required to support and receive FDA approval for a Supplemental New Drug Application to market COPREXA for the treatment of Alzheimer's disease or other disease indications such as idiopathic pulmonary fibrosis, for example. We cannot assure you that we will be able to enroll, dose and/or complete the described Phase II clinical trial, nor be able to conduct and complete substantially larger necessary Phase III clinical trials necessary to demonstrate sufficient safety and efficacy of COPREXA for AD in the U.S. and/or internationally. 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, including risks set forth in our filings with the Securities and Exchange Commission. We cannot assure you that we will be able to successfully develop or commercialize products based on our technologies, including COPREXA, zinc-monocysteine, TRIMESTA, SOLOVAX, EFFIRMA 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, other than as required by law.

(1) Morris et al Arch. Neurol 63:1085-1088; 2006

(2) Squitti et al. Neurology 67:76-82; 2006

Contact Information

  • For Further Information Contact:
    Steve H. Kanzer, CPA, Esq.
    Chairman and Chief Executive Officer
    (734) 332-7800

    Thomas Redington, Ph.D.
    Investor Relations
    Redington, Inc.
    (203) 222-7399