Vandy
07-26-2001, 04:26 PM
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: GLFD <http://finance.yahoo.com/q?s=glfd&d=t> - news </n/g/glfd.html> ) 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® 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 disease.
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 groups.
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 significant.
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 disease.
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.
Contact: Guilford Pharmaceuticals Inc.
Stacey Jurchison 410-631-5022
Angie Rubin 410-631-6449
Internet address: www.guilfordpharm.com (http://www.guilfordpharm.com) <http://www.guilfordpharm.com>
This press release contains forward-looking statements that involve risks and uncertainties, including those described in the section entitled ``Risk Factors'' contained in the Company's Registration Statement on Form S-3 dated June 21, 2001, that could cause the Company's actual results and experience to differ materially from anticipated results and expectations expressed in these forward-looking statements. Among other things, there can be no assurance that NIL-A will be shown in clinical trials to be a safe and effective drug for the treatment of Parkinson's disease or other conditions.
First Clinical Evaluation of Neuroimmunophilin Ligands in Parkinson's Disease
BALTIMORE, July 26 /PRNewswire/ --
Guilford Pharmaceuticals Inc. (Nasdaq: GLFD <http://finance.yahoo.com/q?s=glfd&d=t> - news </n/g/glfd.html> ) 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® 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 disease.
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 groups.
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 significant.
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 disease.
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.
Contact: Guilford Pharmaceuticals Inc.
Stacey Jurchison 410-631-5022
Angie Rubin 410-631-6449
Internet address: www.guilfordpharm.com (http://www.guilfordpharm.com) <http://www.guilfordpharm.com>
This press release contains forward-looking statements that involve risks and uncertainties, including those described in the section entitled ``Risk Factors'' contained in the Company's Registration Statement on Form S-3 dated June 21, 2001, that could cause the Company's actual results and experience to differ materially from anticipated results and expectations expressed in these forward-looking statements. Among other things, there can be no assurance that NIL-A will be shown in clinical trials to be a safe and effective drug for the treatment of Parkinson's disease or other conditions.
Sponsor
Bernie812
07-26-2001, 04:30 PM
IT DOES NOT LOOK GOOD.
BUMMER...............................
BUMMER...............................
Googy
07-26-2001, 06:29 PM
There it is Bernie.Many,as you, will be disappointed.Now we have to concentrate on the other available treatments. " As One door closes,another one opens."
I just read in our local newpaper the view of Stephen J.Forman MD at the City Of Hope Cancer Center In Los Angeles " Why Bush should support life-saving stem research," he can be reached at.....kkoga@coh.org I've never been certain about this.But he tells so much of his Cancer patients who can also be helped with the research from stem cells.I now think I can accept this
I want to see in my lifetime a cure for PD.With Bill it is to late.
Thank you also Vandy,many will read this
love,
Googy
[This message has been edited by Googy (edited 07-26-2001).]
I just read in our local newpaper the view of Stephen J.Forman MD at the City Of Hope Cancer Center In Los Angeles " Why Bush should support life-saving stem research," he can be reached at.....kkoga@coh.org I've never been certain about this.But he tells so much of his Cancer patients who can also be helped with the research from stem cells.I now think I can accept this
I want to see in my lifetime a cure for PD.With Bill it is to late.
Thank you also Vandy,many will read this
love,
Googy
[This message has been edited by Googy (edited 07-26-2001).]
Bernie812
07-28-2001, 01:40 AM
Thanks Googy. Forgive me for what follows, but I need to vent.
Yesterday, I was stunned. Today I'm bewildered.
All this time, effort & money, and with a couple of sentences the drug does not produce significant results? That's it???????? It's just business?????
No, I'm sorry. That's not good enough. Doesn't someone feel a responsibility towards these people that volunteered their bodies for this experiment. What about the patients that experienced good results that were even verified by their doctors? There is some explaining to be done here. If this is the way the whole drug approval process works, then it stinks and is in desperate need of reform. I now understand why the FDA Patient Initiative, mentioned in my other post, is so important.
I know the final decision on PIII has not been made, but this Press Release yesterday was not issued without careful consultation between Guilford and Amgen. I don't believe Amgen will go ahead with anthing less than very significant results. Yesterday was a warning that their not seeing it. Possibly, they will go back, if they haven't already, and do additional research on one of the other generations of compounds they've licensed form Guilford. Some on the MGH board are far more hopeful than me that we'll see PIII.
Some questions I'd like answered.
If one purpose of PII was to determine proper dosing levels, then how would anyone know if that's been reached? Only two dosing levels have been tested on humans so far.
If the high dose produced better results, can a representative group of just 99 people be enough to base a decision on?
I've been in a PD study and had to take the tap test. If you've had too much coffee, not enough sleep, or under a lot of stress, the results can vary. Some people are just not themselves in a doctors office. Not just that, but didn't they state that the participants were mild to moderate patients. What if a fair amount had good tap scores to begin with? How much better would they get. I find it hard to believe that this test carries so much weight. I have a million questions, but mostly I have less faith than ever in the process.
One nagging question I've had all along. Why would a drug that's been touted to be useful for multiple diseases, be tested for only PD? Is it purely a money issue? If so, at least an honest answer should be provided. More than likely, Amgen didn't want to venture into other areas until they had success in one.
One last rag. This one really ticks me off. All I heard this morning on the news was how well Amgens earnings report was. Not a word about another possible disappointment for the PD community. Well................I guess we just have to start yelling a little louder.
There, I feel a little better.
I'll be back.
Bernie812
Yesterday, I was stunned. Today I'm bewildered.
All this time, effort & money, and with a couple of sentences the drug does not produce significant results? That's it???????? It's just business?????
No, I'm sorry. That's not good enough. Doesn't someone feel a responsibility towards these people that volunteered their bodies for this experiment. What about the patients that experienced good results that were even verified by their doctors? There is some explaining to be done here. If this is the way the whole drug approval process works, then it stinks and is in desperate need of reform. I now understand why the FDA Patient Initiative, mentioned in my other post, is so important.
I know the final decision on PIII has not been made, but this Press Release yesterday was not issued without careful consultation between Guilford and Amgen. I don't believe Amgen will go ahead with anthing less than very significant results. Yesterday was a warning that their not seeing it. Possibly, they will go back, if they haven't already, and do additional research on one of the other generations of compounds they've licensed form Guilford. Some on the MGH board are far more hopeful than me that we'll see PIII.
Some questions I'd like answered.
If one purpose of PII was to determine proper dosing levels, then how would anyone know if that's been reached? Only two dosing levels have been tested on humans so far.
If the high dose produced better results, can a representative group of just 99 people be enough to base a decision on?
I've been in a PD study and had to take the tap test. If you've had too much coffee, not enough sleep, or under a lot of stress, the results can vary. Some people are just not themselves in a doctors office. Not just that, but didn't they state that the participants were mild to moderate patients. What if a fair amount had good tap scores to begin with? How much better would they get. I find it hard to believe that this test carries so much weight. I have a million questions, but mostly I have less faith than ever in the process.
One nagging question I've had all along. Why would a drug that's been touted to be useful for multiple diseases, be tested for only PD? Is it purely a money issue? If so, at least an honest answer should be provided. More than likely, Amgen didn't want to venture into other areas until they had success in one.
One last rag. This one really ticks me off. All I heard this morning on the news was how well Amgens earnings report was. Not a word about another possible disappointment for the PD community. Well................I guess we just have to start yelling a little louder.
There, I feel a little better.
I'll be back.
Bernie812
Googy
07-28-2001, 05:55 PM
Bernie,
I agree with you .One more thing you need to do.Condense what you just posted and send to your local newspaper.I have done that over the years.The public needs to be informed.Don't forget to put the rise in stock.
Googy
I agree with you .One more thing you need to do.Condense what you just posted and send to your local newspaper.I have done that over the years.The public needs to be informed.Don't forget to put the rise in stock.
Googy
Lory
07-29-2001, 10:59 AM
Originally posted by Vandy:
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: GLFD <http://finance.yahoo.com/q?s=glfd&d=t> - news </n/g/glfd.html> ) 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® 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 disease.
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 groups.
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 significant.
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 disease.
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.
Contact: Guilford Pharmaceuticals Inc.
Stacey Jurchison 410-631-5022
Angie Rubin 410-631-6449
Internet address: www.guilfordpharm.com (http://www.guilfordpharm.com) <http://www.guilfordpharm.com>
This press release contains forward-looking statements that involve risks and uncertainties, including those described in the section entitled ``Risk Factors'' contained in the Company's Registration Statement on Form S-3 dated June 21, 2001, that could cause the Company's actual results and experience to differ materially from anticipated results and expectations expressed in these forward-looking statements. Among other things, there can be no assurance that NIL-A will be shown in clinical trials to be a safe and effective drug for the treatment of Parkinson's disease or other conditions.
Though extremely dissappointing, thank you for the post. Now we have to fight yet another battle, it seems. Lory
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: GLFD <http://finance.yahoo.com/q?s=glfd&d=t> - news </n/g/glfd.html> ) 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® 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 disease.
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 groups.
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 significant.
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 disease.
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.
Contact: Guilford Pharmaceuticals Inc.
Stacey Jurchison 410-631-5022
Angie Rubin 410-631-6449
Internet address: www.guilfordpharm.com (http://www.guilfordpharm.com) <http://www.guilfordpharm.com>
This press release contains forward-looking statements that involve risks and uncertainties, including those described in the section entitled ``Risk Factors'' contained in the Company's Registration Statement on Form S-3 dated June 21, 2001, that could cause the Company's actual results and experience to differ materially from anticipated results and expectations expressed in these forward-looking statements. Among other things, there can be no assurance that NIL-A will be shown in clinical trials to be a safe and effective drug for the treatment of Parkinson's disease or other conditions.
Though extremely dissappointing, thank you for the post. Now we have to fight yet another battle, it seems. Lory