Full Press Release Details
Therapeutics' COPREXA Pivotal Clinical Trial Results Presented at NIH-Sponsored
Wilson's Disease Association Conference
Endpoint Achieved, a Statistically Significant Reduction (p<0.05) in
Neurologic Worsening Compared to Copper Chelator Trientine
Arbor, Michigan, November 7, 2006 -- Pipex Therapeutics, Inc. (OTC BB: SFPH),
specialty pharmaceutical company developing innovative late-stage drug
candidates for the treatment of neurologic and fibrotic diseases, announced
today that the pivotal clinical trial results of its lead drug candidate,
COPREXA (oral tetrathiomolybdate) a new treatment being developed for
initially-presenting neurologic Wilson's Disease, were presented at the Wilson's
Disease Association Annual Meeting in Bethesda, MD.
Neurologically-presenting
Wilson's disease, a genetic disease involving impaired hepatic copper excretion
results in excessive levels of toxic free copper in the systemic circulation
CNS. These increased levels of free copper cause significant neurologic damage,
resulting in tremors, impaired speech, and Parkinson's like dystonia.
double-blind, randomized, comparator, pivotal clinical trial, 48 Wilson's
disease patients were initially treated with either trientine (Syprine ), a
copper chelator approved as second line therapy for the treatment of Wilson's
disease, or COPREXATM.
acetate) maintenance therapy followed for a period of two years. Patients
treated with trientine demonstrated a 26% incidence (6 of 23) of neurologic
worsening. On the other hand, patients treated with COPREXATM
demonstrated only a 4.0% incidence (one of 25) of neurologic worsening
(p<0.05). This pivotal study also suggested that neurologic deterioration
during the initial treatment phase is an important prognostic indicator of
survival, a critical long-term clinical outcome for Wilson's disease patients.
results from this study are consistent with our earlier clinical trial in which
COPREXA was administered to 55 initially-presenting neurologic Wilson's disease
maintenance therapy followed for a period of two years. During that follow-up
period, neurologic function was assessed with scored neurologic and speech
tests. A highly statistically significant improvement was reached with respect
to annual quantitative neurologic scores, as compared to baseline (p<0.002).
Annual quantitative speech scores also yielded a highly statistically
significant improvement (p<0.001) as compared to baseline. Importantly, only
2 of the 55 patients, or 3.6% of the patients treated with COPREXATM,
further neurologic deterioration. This compares very favorably to the estimated
52% incidence of neurologic deterioration in patients treated with
penicillamine, the currenty approved first line therapy for Wilson's disease.
these clinical trials point to COPREXATM
better choice than trientine or penicillamine for preserving neurologic function
in Wilson's disease patients who present with neurologic disease
"Initially-presenting
neurologic Wilson's disease is a serious CNS disorder adversely affecting the
quality of life of these patients, which if diagnosed can be managed with
adequate drug therapy, said George J. Brewer, MD, Emeritus Professor of Human
Genetics at the University of Michigan and inventor of COPREXA and the
article's lead author. The results of this study confirm earlier findings of
efficacy and safety of COPREXA . With no adequate approved treatment, this
represents an important step forward for patients suffering from neurologic
disease is an autosomal recessive genetic disease attributable to mutations
Worldwide, it is estimated that there are between 10 million and 30 million
carriers of the heterozygous mutated gene. These mutations lead to an inability
to properly clear excess free copper from the body
the liver into the bile and stool. As a result, copper
accumulates in the liver and elevated levels of toxic free copper enter the
systemic circulation, cross the blood brain barrier, and enter the cerebral
spinal fluid (CSF) and brain. Elevated levels of free copper in the CSF causes
myriad of neurologic toxicities due to the brain's sensitivity to the
of free copper. Given the rarity of Wilson's
and the fact that it is easily mistaken for other illnesses, patients often
undiagnosed for decades.
half of newly-diagnosed Wilson's patients initially present with neurologic
symptoms and the remainder generally present with hepatic symptoms. Psychiatric
symptoms of neurologically-presenting Wilson's patients will generally precede
neurologic symptoms by months or years and may include loss of emotional
control, temper tantrums, emotional outbursts, bouts of crying, severe
depression, suicidal ideation, loss of inhibitions, delusions, hallucinations
and loss of ability to focus on tasks. Neurologic symptoms later develop as
result of neurodeneration in the basal ganglia of the brain and include impaired
speech, tremor, dystonia, incoordination and dysphagia. Paralysis may ultimately
proper treatment, Wilson's disease is usually fatal by the age of 30. However,
if treatment is begun early enough, symptomatic recovery is usually complete
a life of normal length and quality can be expected.
the FDA approved therapies, such as trientine or penicillamine which are
currently available for Wilson's disease offer suboptimal, and indeed
problematic, treatment options for initially-presenting Wilson's patients that
present with neurologic symptoms.
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.
developing COPREXA for fibrotic
disorders based upon the rationale that
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
(SPARC), NF B, TGF- , FGF-2, IL-1, IL-6, IL-8, and connective tissue growth
COPREXA has recently completed a phase II clinical trial for the treatment of
refractory idiopathic pulmonary fibrosis (IPF), a fatal respiratory disease.
COPREXA is also in a phase II clinical trial for the treatment of primary
biliary cirrhosis (PBC), a fibrotic disease of the hepatic system.
Pipex Therapeutics, Inc.
Therapeutics, 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