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Guilford Pharmaceuticals Announces Completion Of NIL-A Phase II Clinical

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    Guilford Pharmaceuticals Announces Completion Of NIL-A Phase II Clinical

    Guilford Pharmaceuticals Announces Completion Of NIL-A Phase II Clinical
    Trial for Parkinson's Disease

    First Clinical Evaluation of Neuroimmunophilin Ligands in Parkinson's Disease

    BALTIMORE, July 26 /PRNewswire/ --

    Guilford Pharmaceuticals Inc. (Nasdaq: <A HREF="aol://4785:GLFD">GLFD</A> )
    announced today that Amgen Inc. has completed a Phase II clinical trial of
    NIL-A, the neuroimmunophilin ligand licensed to it by Guilford
    Pharmaceuticals, in patients with Parkinson's disease. This trial is the
    first clinical evaluation of a neuroimmunophilin ligand in the treatment of
    Parkinson's disease.

    About the NIL-A Phase II Clinical Trial

    The clinical trial conducted by Amgen is a Phase II, randomized, double-
    blind, placebo- controlled evaluation of the safety, pharmacokinetics and
    efficacy of NIL-A in patients with mild to moderate Parkinson's disease.

    Phase II clinical trials of a drug are usually conducted to extend the safety
    evaluation conducted in Phase I, to determine a dosing regimen for future
    clinical trials, and to explore the potential efficacy of the drug in a
    targeted patient population. The efficacy evaluation centers on determining
    the clinical benefit of treatment, if any, and whether or not all patients or
    a subgroup appear to benefit. Phase II trials are usually exploratory or
    hypothesis generating. Confirmatory evidence, gathered in Phase III trials,
    is almost always needed before final conclusions can be drawn about the
    safety and efficacy of a new drug.

    At the 42 participating medical centers in the NIL-A Phase II trial, patients
    were screened to determine their eligibility for the study and informed
    consent was obtained from each patient who was offered and accepted
    enrollment. Patients then received a thorough examination, including a
    neurological exam, to determine the extent and severity of their disease and
    all drugs then being administered were recorded. To be eligible, patients
    had to be optimally treated with antiparkinsonian drugs and have stable
    clinical symptoms. Upon completing the baseline evaluation, patients were
    randomly assigned to receive either placebo tablets, 200 mg of NIL-A, or
    1,000 mg of NIL-A four times a day for 24 weeks. The randomization scheme
    was blocked by imaging status (see below) but not by treatment center.

    Subsequently, all patients were periodically evaluated by neurologists expert
    in Parkinson's disease to determine if they had experienced any side effects
    from treatment, to measure their blood levels of NIL-A, and to determine if
    they had experienced any change in their symptoms of Parkinson's disease.

    SPECT brain scans were obtained with 123I Beta-CIT (DOPASCAN(R) Injection) in
    a subset of the patients to obtain a measure of the density of dopamine nerve
    terminals in the region of the brain that deteriorates in Parkinson's

    After six months of treatment, final clinical examinations and SPECT scans
    were obtained and treatment was discontinued. Patients were followed for 28
    days after treatment and then exited from the trial.

    There were 300 patients enrolled in the trial, 101 were assigned to the
    placebo group, 100 to the low dose group, and 99 to the high dose group.
    SPECT scans were obtained in 105 subjects equally divided among the treatment

    The two primary clinical hypotheses tested in this trial were that 6 months
    of treatment with NIL-A would result in at least a 4 point improvement when
    compared with placebo in the UPDRS Motor Subscale measured before patients
    took their first daily dose of antiparkinsonian medication, and that NIL-A
    would be safe and well tolerated at doses up to 1000 mg four times a day for
    6 months. The a priori efficacy hypothesis was established based on expert
    advice and prior experience with the development of other classes of
    antiparkinsonian drugs, although there was no prior clinical experience with
    NIL-A to generate the primary efficacy hypothesis. Secondary efficacy
    endpoints identified in the analytical plan for the trial were: 123I Beta CIT
    SPECT scans, total UPDRS score, bilateral finger tapping, dyskinesia rating
    scale, Hoehn & Yahr rating scale and a quality of life measure obtained from
    a questionnaire.

    The frequency and severity of reported adverse events were similar in all
    three treatment groups except that patients in the high dose NIL-A group
    experienced an increased incidence of transient nausea or indigestion. The
    mean change in UPDRS motor score was -1.05 in placebo treated patients and
    0.25 and -0.35 in the low dose and high dose patients respectively. (p=0.2)
    An increase in score indicates worsening disease. The mean percent change in
    the density of dopamine nerve terminals as measured by SPECT was +3.4% in
    placebo patients, +6.3% in low dose patients and +9.4% in the high dose group
    after 12 weeks of treatment. (n=30, 10 per group, p=0.4) the corresponding
    changes at 24 weeks were -0.15%, -1.2% and +2.5%. (n=105, 35 per group,
    p=0.7). The Hoehn & Yahr score improved (i.e., went down) during the trial
    in 11% of placebo patients, 17% of low dose patients, and 21% of the high
    dose patients. The difference between the high dose group and the placebo
    group was significant after adjustment for age, duration of Parkinson's
    disease symptoms, and Hoehn & Yahr score at baseline (p=0.028). The changes
    in the dyskinesia scores and finger tapping tests were not statistically

    Subgroups of patients stratified by age, disease severity, duration of
    symptoms, and type of antiparkinson's treatment are currently being analyzed.

    These results suggest that NIL-A at doses up to 1000 mg taken orally four
    times a day for 6 months is well-tolerated but does not produce a substantial
    reversal of the motor symptoms of Parkinson's disease.

    About Parkinson's Disease

    Parkinson's disease is a chronic, progressive degenerative disorder that
    involves a specialized region of the brain that controls muscle tone and
    coordination. Most patients are affected in mid-life and usually develop
    hand tremors, muscle rigidity, and postural instability, among the many
    manifestations of the disease. The disease is caused by the degeneration of
    nerve cells that use dopamine as a chemical messenger. Treatment currently
    consists of administering drugs that increase the amount of dopamine in the
    affected regions of the brain or substitute for the lost dopamine.
    Unfortunately, there are no current treatments that can reverse, or even slow
    down, the progressive degeneration of the dopamine nerve cells in Parkinson's

    About Neuroimmunophilin Ligands

    Neuroimmunophilin ligands are small molecules that in preclinical experiments
    have been shown to be orally-bioavailable, cross the blood-brain barrier, and
    repair and regenerate damaged nerves without affecting normal nerves. In
    1997, Guilford entered into a collaboration with Amgen for the research,
    development and commercialization of a broad class of neuroimmunophilin
    ligands, for a range of indications, including Parkinson's disease,
    Alzheimer's disease, spinal cord injury, brain trauma, and other diseases and
    conditions. Amgen commenced the current Phase II trial for NIL-A for
    Parkinson's disease in the summer of 2000.

    Guilford Pharmaceuticals is a biopharmaceutical company engaged in the
    development of polymer-based therapeutics for cancer, and novel products for
    the diagnosis and treatment of neurological diseases, including Parkinson's
    disease, Alzheimer's disease, stroke, severe head trauma, spinal cord
    injuries, multiple sclerosis and peripheral neuropathies.