May 8, 2017
Otsuka Pharmaceutical and H. Lundbeck reported results of two phase III clinical trials of brexpiprazole in the treatment of agitation in patients with dementia related to Alzheimer’s disease. Both trials were randomized, double-blind, placebo-controlled studies that enrolled a combined total of approximately 700 participants. Trial participants were between 51 and 90 years of age with a diagnosis of probable Alzheimer’s disease and symptoms of agitation. These studies were conducted in multiple countries in North America and Europe, and in the Russian Federation. One of the trials studied fixed doses of either 1 or 2mg per day of brexpiprazole or placebo, while the other trial studied a flexible-dose range of 0.5mg, 1mg or 2mg per day of brexpiprazole, or placebo. Both trials were 12 weeks in duration. In the first study, the improvement in the primary endpoint of Cohen-Mansfield Agitation Inventory (CMAI) for 2mg brexpiprazole was statistically better than placebo (p<0.05) and appeared more robust than the improvements on the key secondary endpoint of Clinical Global Impression-Severity of Illness (CGI-S) (p>0.05). In the second study, the improvements in the primary endpoint of CMAI (p>0.05) appeared less robust than improvements observed on the key secondary endpoint of CGI-S (p<0.05). In both studies, there was variability in the data from different countries, perhaps associated with differing standards of care; the data from Russian sites showed especially poor separation between placebo and drug. Regarding safety and tolerability, both studies confirmed the profile of brexpiprazole as observed in the clinical trials for schizophrenia and for adjunctive treatment of major depressive disorder (MDD). The most common adverse events in patients receiving brexpiprazole versus placebo (incidence >3% and greater than placebo) were insomnia (4.7% vs. 3.3%), agitation (3.5% vs. 2.9%) and somnolence (3.3% vs. 2.2%). Overall mortality during the studies was 0.86% and none of the deaths were considered to be related to treatment. The companies plan to meet with the FDA to discuss the results of the studies.
June 20, 2016
Avanir Pharmaceuticals released results of an open-label, multicenter study of NUEDEXTA (dextromethorphan hydrobromide/quinidine sulfate) for Alzheimer’s disease (AD) and other dementias, stroke and traumatic brain injury (TBI). PRISM II was designed to evaluate the safety, tolerability and effectiveness of
NUEDEXTA capsules that contains 20mg dextromethorphan hydrobromide (DM) and 10mg quinidine sulfate (Q). The nationwide, open-label study enrolled 367 patients at 74 study centers. The Center for Neurologic Study Lability Scale (CNS-LS) score improved significantly from a mean of 20.5 at baseline to 12.8 (p<0.001) at the 90-day endpoint, which is consistent with results seen with NUEDEXTA in the phase III trial. PBA episodes were reduced by 72.6% (p<0.001) compared to baseline at the 90-day endpoint. PBA episode counts over the seven days prior to study visit decreased from a median of 12 at baseline to two at the 90-day endpoint; 35.5% of patients experienced no PBA episodes at the 90-day endpoint. The adverse event (AE) profile in PRISM II was consistent with the known safety profile of NUEDEXTA. The most frequently occurring AEs were diarrhea (5.4%), headache (4.1%), urinary tract infection (2.7%) and dizziness (2.5%); 9.8% of patients had AEs that led to discontinuation. Serious AEs were reported in 6.3% of patients; however, none were considered to be related to NUEDEXTA treatment.
November 30, 2015
Anavex Life Sciences has reported results
of a phase IIa study of ANAVEX 2-73 for
Alzheimer’s disease targeting sigma-1 and
muscarinic receptors. In Part A of the study,
32 participants were administered ANAVEX
2-73 orally (30mg/50mg) and IV (3mg/5mg)
in a randomized, open-label, two-period,
cross-over trial separated by a wash-out with
adaptive study design lasting up to 36 days
for each participant. In Part B of the study, all
participants were administered ANAVEX 2-73
daily orally. Positive effects on cognition were
supported by highly statistically significant
biomarker effects of treatment at week five
on one event-related potential (ERP) measure
with a p-value of p<0.0007 and improvement
in the P300 signal. All patients who completed
PART A volunteered to continue in the
longitudinal PART B extension study. Initial
analysis of phase IIa data demonstrated that
the study met the primary objective of safety
as ANAVEX 2-73 was well-tolerated and results
were consistent with prior phase I clinical trial
November 9, 2015
Transition Therapeutics Ireland has
issued results of a phase II/III study of
ELND005 in Alzheimer’s disease (AD) patients
with moderate or severe agitation and
aggression. The placebo-controlled study
enrolled 350 AD subjects. The NPIC A+A
scale is an aggregate score of severity related
to 21 behavioral symptoms. Analysis of
the patient population with a baseline NPIC
A+A < 22 showed that the major symptoms
manifested were upset, stubborn, resistance,
ask and shouting, and the remaining 16
behavioral symptoms were much less prevalent
and had lower severity. As the baseline
severity of NPIC A+A increased above 22 in
AD patients, particularly above 26, many of
the verbal and physical aggression items,
as well as the excessive motor activities,
also increased in prevalence and severity.
In that population, 20 of the 21 symptoms
measured by the NPIC A+A numerically
favored ELND005 relative to placebo. These
data demonstrated that ELND005 appeared
to have a more pronounced effect on the
verbal and physical aggression symptoms,
as well as the excessive motor activities, that
were more prevalent in AD patients with
increasing agitation and aggression disease
severity. The overall incidence of treatment
emergent adverse events (TEAEs) in the
ELND005 group and the placebo group were
similar (56.6% v. 54.3%), as was the incidence
of study drug-related TEAEs (13.1% v.
14.9%). Most TEAEs were mild or moderate
in severity. The most common TEAEs in the
ELND005 group that were 5% in incidence
were: agitation (8% v. 7.4% in placebo), diarrhea
(8% v. 2.9% in placebo), urinary tract
infection (6.9% v. 4% in placebo) and falls
(6.3% v. 5.1% in placebo). The analysis will
serve as the basis for patient selection in a
phase III clinical study.
November 2, 2015
Transition Therapeutics has issued
results of a phase II/III study of ELND005 in
Alzheimer’s disease (AD) patients with moderate
or severe agitation and aggression.
The randomized, double-blind, placebo-controlled
study enrolled 350 AD patients
(175 subjects per study arm). Subjects
received either placebo or a fixed dosing
regimen of ELND005. The fixed dosing regimen
consisted of a loading dose of 1000mg
twice daily (BID) for four weeks, followed by
a maintenance dose of 250mg BID for a subsequent
eight weeks. The primary efficacy
endpoint (12 week change from baseline
of the Neuropsychiatric Inventory Clinician
(NPIC) A+A scale) was not achieved in the
overall study population of AD patients with
moderate or severe agitation and aggression.
A post-hoc analysis demonstrated that
ELND005 provided a clinically meaningful
5.1 point improvement relative to placebo
on the NPIC A+A scale (p=0.047) in a severe
agitation and aggression population. An
evaluation of progressively severe patient
subsets with baseline NPIC A+A scores
greater than 22 showed a consistent and
greater improvement over the 5.1 points
observed in the overall severe population. A
phase III study is planned.
November 3, 2014
Avanir Pharmaceuticals issued results
from a phase II study of AVP-923 for the
treatment of agitation in patients with
Alzheimer’s disease. The 10-week, randomized,
multicenter study utilized a sequential parallel
comparison design intended to reduce
placebo response rates, and consisted of two
consecutive double-blind treatment stages,
each of five-week duration. A total of 220
Alzheimer’s patients in the U.S. were enrolled.
Eligible patients were initially randomized
in a 3:4 ratio to receive either AVP-923 (dose
escalated from DM 20mg/Q 10mg to DM
30mg/Q 10mg) or placebo. At the end of
week five, patients who initially received
placebo were stratified according to their
response to treatment and subsequently
re-randomized in a 1:1 ratio to receive either
AVP-923 or placebo for the remainder of the
study (an additional five weeks of treatment).
Patients who initially received AVP-923
continued to receive AVP-923 DM 30mg/Q
10mg for the remainder of the study. AVP-923
showed a statistically significant benefit on
the agitation/aggression domain of the Neuropsychiatric
Inventory (NPI) (primary endpoint;
p=0.00008). The NPI agitation/aggression
score was reduced by 3.3 points from
baseline in AVP-923 treated patients at week
five (stage 1; p=0.0002 v. placebo) and was
reduced by two points in stage 2 (p=0.021).
The change in the NPI agitation/aggression
score corresponds to a mean (SD) reduction
from baseline of 47% (43.1%) for AVP-923
v. 22% (50.8%) for placebo in stage 1, and
26% (67.5%) for AVP-923 v. 6.7% (77.9%) for
placebo in stage 2. AVP-923 also demonstrated
significant improvements v. placebo
on the following outcomes: NPI total score
(p=0.014), NPI4A (p=0.001), NPI4D (p<0.001),
clinical global impression of change-agitation
(p=0.0003), patient global impression of
change (p=0.001) and measures of caregiver
burden (p<=0.05). AVP-923 was generally
safe and well-tolerated and associated with
a low rate of discontinuation from the study
(11.8%). The company is working with the
FDA and EMA to advance the program.
September 22, 2014
Avanir Pharmaceuticals reported results
of a phase II trial of AVP-923 for agitation related
to Alzheimer’s disease. The trial was a 10-
week, multicenter, randomized, double-blind,
placebo-controlled study utilizing a SPCD
design intended to reduce placebo response
rates, enrolling 220 Alzheimer’s patients in the
U.S. Patients were initially randomized 3:4 to
receive either AVP-923 (dose escalated from
DM 20mg/ Q 10mg to DM 30mg/ Q 10mg)
or placebo. At the end of week five, patients
who initially received placebo were stratified
according to their response to treatment and
subsequently re-randomized 1:1 to receive
either AVP-923 or placebo for the remainder
of the study. Patients who initially received
AVP-923 continued to receive AVP-923 DM
30mg/Q 10mg for the remainder of the study.
Treatment with AVP-923 was associated with
significantly reduced agitation as measured
by the primary endpoint, the agitation/aggression
domain score of the neuropsychiatric
inventory (NPI) compared to placebo
(p=0.00008). The reduction in agitation was
observed in both stage one (p=0.0002) and
stage two (p=0.021) of the sequential parallel
comparison study design. In addition,
improvements also were seen in a majority
of the secondary endpoints including the NPI
total score (p=0.014), clinical global impression
of change-agitation (p=0.0003), patient
global impression of change (p=0.001) and
measures of caregiver burden (p≤0.05).
June 30, 2014
Neurim Pharmaceuticals released results of a phase II trial of add-on Circadin (Prolonged Release melatonin 2mg) to standard therapy in Alzheimer’s disease (AD) patients. The randomized, placebo-controlled trial enrolled 80 patients diagnosed with mild-to-moderate AD, with and without insomnia co-morbidity, receiving standard therapy (acetylcholinesterase inhibitors with or without memantine), who were randomly assigned in a double-blind manner to 2mg of Circadin or placebo treatment nightly for 24 weeks. Patients treated with Circadin for six months had significantly better cognitive performance than those with placebo as measured by Instrumental Activities of Daily Living (IADL) and Mini Mental State Examination (MMSE). Mean Alzheimer’s Disease Assessment Scale—cognition (ADAS-
Cog) did not differ between groups. Sleep efficiency as measured by Pittsburgh Sleep Quality Index (PSQI) Component 4 also improved with Circadin. In a subgroup of patients suffering from comorbid insomnia, Circadin treatment resulted in significant and clinically meaningful
effects v. placebo in mean IADL (p=0.032), MMSE (+1.5 v. -3 points, p=0.0177) sleep efficiency (p=0.04) and median ADAS-Cog values (-3.5 v. +3 points, p=0.045).
July 22, 2013
Merck issued results from a phase Ib trial of MK-8931 for the treatment of Alzheimer’s disease (AD). The randomized, double-blind, placebo-controlled multiple-dose study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamic profile of MK-8931 in patients with mild to moderate AD (n=32). Patients were randomized to receive one of three doses (12mg, 40mg and 60mg) orally of MK-8931 or placebo once-daily for seven days. Administration of MK-8931 at doses of 12mg, 40mg and 60mg resulted in a dose-dependent and sustained reduction in the levels of Ab40, a measure of BACE1 activity, in CSF from baseline of 57%, 79% and 8%, respectively. No serious adverse events or study discontinuations due to adverse events were recorded. Further evaluation of MK-8931 continues in an ongoing phase II/III trial in patients with mild to moderate AD.
October 15, 2012
Eli Lilly issued results from a phase III trial of solanezumab for Alzheimer’s disease. This double-blind, placebo-controlled study, Expedition 2, enrolled 1,040 patients with mild to moderate Alzheimer’s. Subjects received either solanezumab 400mg and basic standard care, or placebo and basic standard care, every four weeks for 18 months. Results showed a 20% reduction in cognitive decline in patients with mild Alzheimer’s taking solanezumab, but the treatment difference was not statistically significant (p=0.120). In the pre-specified secondary endpoint of ADCSADL, there was a 19% reduction in functional decline in patients with mild Alzheimer’s treated with solanezumab, as compared with placebo; this difference was not statistically significant (p=0.076). The drug was well tolerated. The most frequent adverse events were angina and vasogenic edema.
July 30, 2012
EnVivo Pharmaceuticals released results from a phase IIb trial of EVP-6124 for the treatment of Alzheimer’s disease. This double-blind, placebo-controlled study enrolled 409 patients with mild to moderate Alzheimer’s disease. Subjects received EVP-6124 0.3mg, 1.0mg or 2.0mg once daily or placebo for six months. The 2.0mg dose met both primary endpoints with statistically significant positive effects on cognition (p=0.0189) as measured by the Alzheimer’s Disease Assessment Scale-Cognitive subscale-13 (ADAS-Cog-13) and clinical function (p=0.0253) as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). The 2.0mg dose also showed an improvement in cognition composite (p=0.0037), memory composite (p=0.0088) and executive function composite (p=0.0427). EVP-6124 was well-tolerated. The most frequent adverse events were mild to moderate gastrointestinal side effects. Based on these data, EnVivo will continue to advance EVP-6124 and is planning a phase III trial for 2013.
July 23, 2012
EnVivo Pharmaceuticals announced results from a phase IIb trial of EVP-6124 in Alzheimer’s disease. This multi-center, dose-ranging, placebo-controlled, six-month study enrolled 409 participants with mild to moderate Alzheimer’s disease, some of whom were receiving acetylcholinesterase inhibitor (AChEI) treatments (donepezil and rivastigmine) as well as some not on AChEIs treatment. The subjects were administered 0.3mg, 1.0mg, 2.0mg or placebo once daily for 183 days (24 weeks). Primary efficacy measures were determined by the ADAS-Cog scale. Treatment with the 2.0mg dose met both of the trial’s primary endpoints at 23 weeks with statistically significant positive effects on cognition (p=0.0189) as measured by ADAS-Cog-13, and clinical function (p=0.0253) as measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB). The 0.3mg and 1.0mg doses demonstrated positive trends that did not achieve statistically significant improvements compared to placebo. The drug was generally safe and well tolerated, with some mild to moderate gastrointestinal events reported in the 1.0mg and 2.0mg treatment groups. EnVivo is planning to initiate a phase III trial of EVP-6124 in 2013.
June 4, 2012
Lundbeck reported results from a phase II trial of Lu AE58054 in conjunction with donepezil for the treatment of Alzheimers disease. This multinational, randomized, fixed dose, placebo-controlled trial enrolled 278 patients with moderate Alzheimers disease. Subjects received Lu AE58054 plus 10mg/day donepezil or placebo plus 10mg/day donepezil for 24 weeks. Lu AE58054 (plus donepezil) demonstrated statistically significant improvements in cognitive function in Alzheimers disease compared to placebo (plus donepezil), as assessed by ADAS-cog. The drug was well tolerated at the selected dose. Based on these data, Lundbeck will initiate a major pivotal clinical program potentially including development and commercial partnerships.
October 17, 2011
Roche reported results from a phase I trial of gantenerumab under development for Alzheimers disease. The trial enrolled 16 subjects with mild to moderate Alzheimer's disease who received one of two doses of gantenerumab or placebo for six months. Data showed that gantenerumab treatment resulted in a dose-dependent reduction of brain amyloid whereas amyloid load increased in subjects receiving placebo treatment.
April 25, 2011
AB Science reported results from a phase II trial of mastinib for Alzheimer's disease (AD). This randomized, placebo-controlled trial enrolled 35 subjects with mild to moderate AD across study centers in France. The subjects received mastinib as an adjunct to cholinesterase inhibitor and/or memantine treatment for 24 weeks. Improvement in cognitive function and functional capacity was seen in the masitinib treatment group when compared to a placebo group. Sustained and statistically significant responses were reported on the Alzheimers Disease Assessment Scale (ADAS-Cog), as well as the mean change in ADAS-Cog, the minimental state examination (MMSE) and Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) values relative to baseline.
August 16, 2010
Elan and Transition Therapeutics reported results from a phase II trial of AZD-103 for the treatment of Alzheimer's disease. This placebo-controlled, randomized, multiple-dose study, AD201, enrolled 353 subjects with mild-to-moderate disease. The subjects received AZD-103 twice daily (250, 1000 or 2000 mg) or placebo. However, following an interim safety review, the two highest doses of AZD-103 were discontinued and subjects treated at this dose were withdrawn from the study. The final analysis was based on a total of 166 subjects who received either 250mg twice daily (bid) or placebo for up to 18 months. The study's cognitive and functional co - primary endpoints did not achieve statistical significance. However, the 250mg twice daily dose demonstrated a biological effect on amyloid-beta protein in the cerebrospinal fluid (CSF), in a subgroup of patients who provided CSF samples. This dose achieved targeted drug levels in the CSF, and showed some effects on clinical endpoints.
September 22, 2008
Tagacept and AstraZeneca released negative results from a phase IIb trial of AZD3480 for the treatment of Alzheimers disease (AD). This randomized, double blind, placebo controlled, dose-finding study, dubbed Sirocco, enrolled 567 subjects with mild to moderate AD in Western Europe, Eastern Europe and Canada. The subjects received one of three doses of AZD3480, donepezil (active comparator) or placebo and dosed over 12 weeks. The primary outcome was a statistically significant change from baseline after 12 weeks on the Alzheimer's Disease Assessment Scale (ADAS-Cog). Neither AZD3480 nor donepezil reached the primary endpoint. Improvements on the secondary outcome measures, ADCS-CGIC (Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change) and MMSE (Mini Mental State Examination), were reached by two of the three tested AZD3480 doses. Of these, the middle dose performed best on both measures (0.5 point improvement, ADCS-CGIC and 0.9 point improvement, MMSE). Treatment was generally safe and well tolerated. The companies plan to fully analyze the data in order to determine a future course of action.
July 21, 2008
Myriad reported negative results from a phase III trial of Flurizan for the treatment of Alzheimer's disease. This randomized, double-blind, placebo controlled study enrolled 1,684 subjects with mild Alzheimer's across several international sites. The subjects received 800 mg of Flurizan or placebo, orally, twice daily, for 18 months. The study failed to meet the primary endpoints of cognition and activities of daily living as well as the secondary endpoints of global function and cognition. Flurizan was generally well tolerated. Based on the results, Myriad plans to discontinue the development of Flurizan.
June 23, 2008
Elan and Wyeth released mixed results from a phase II trial of bapineuzumab for the treatment of Alzheimers disease. This randomized, double-blind, placebo controlled, multiple ascending dose study enrolled 240 subjects in the United States. The subjects received one of four doses of bapineuzumab (0.15 mg/kg, 0.5 mg/kg, 1.0 mg/kg and 2.0 mg/kg) or placebo. The primary efficacy endpoints were change from baseline in Alzheimers Disease Assessment Scale (ADAS-cog) and Disability Assessment Scale for Dementia (DAD) in the 0.5 mg/kg, 1.0 mg/kg and 2.0 mg/kg dose groups compared to placebo at 18 months. The study did not attain statistical significance on the primary efficacy endpoints in the overall study population. However, statistically significant benefits were observed in certain subgroups. In non-carriers of the Apolipoprotein E4 (ApoE4) allele, post-hoc analyses showed statistically significant benefits on several efficacy endpoints, including ADAS-cog. A favorable directional change was seen on the DAD scale. In non-carriers of the ApoE4 allele, preliminary evaluation of MRI results showed less loss of brain volume among treated subjects versus placebo subjects, a finding that was statistically significant. Treatment was generally well tolerated. In non-carriers, the serious adverse events profile was similar between the placebo and treated groups. In carriers serious adverse events were more frequent in the treatment group compared to the placebo group. Elan and Wyeth plan to move the development of bapineuzumab into phase III trials.
April 28, 2008
Baxter issued positive results from a phase II trial of GAMMAGARD LIQUID and GAMMAGARD S/D for the treatment of Alzheimers disease. This double-blind, placebo-controlled trial enrolled twenty-four subjects with mild to moderate Alzheimers disease, who were maintained on standard treatment therapy, in the United States. The subjects were randomized to receive GAMMAGARD LIQUID, GAMMAGARD S/D (solvent/detergent) or saline placebo for six months. The study included a comparison of four dosing regimens of GAMMAGARD, with doses ranging from 0.2 g/kg every two weeks to 0.8 g/kg every month. Cognitive, behavioral and functional measures were collected at baseline, three months and six months of treatment. The primary endpoints were improvements in cognitive function (as measured by the ADAS-cog) and global impression of change (as assessed by the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) change rating) over placebo. The secondary endpoints measured changes in beta-amyloid and anti-amyloid antibody levels in blood and cerebrospinal fluid. After six months, the group of subjects treated with GAMMAGARD S/D and GAMMAGARD LIQUID averaged 1.52 points higher than placebo-treated subjects (+0.27 versus -1.25) on the ADCS-CGIC score. The average change in ADAS-Cog score at six months of treatment was numerically improved in subjects treated with GAMMAGARD S/D and GAMMAGARD LIQUID than placebo (-0.38 versus +2.61), although this difference did not reach statistical significance. In addition, the levels of antibodies against beta-amyloid increased in the cerebrospinal fluid and blood of subjects treated with GAMMAGARD S/D and GAMMAGARD LIQUID, while the levels of beta-amyloid in the blood increased. Treatment was determined to be safe and well tolerated. Based on the results, Baxter is planning to commence a phase III trial later in 2008.
March 3, 2008
Prana reported positive results from a phase IIa trial of PBT-2 for the treatment of Alzheimers disease. This randomized, double blind, placebo-controlled trial enrolled seventy eight subjects across seven sites in Sweden and Australia. The subjects received PBT-2 (50 mg), PBT-2 (250 mg) or placebo once daily for three months. PBT-2 was determined to be safe and well tolerated at both doses, with a safety profile similar to placebo. PBT-2 also reduced Abeta 42 in the cerebrospinal fluid with statistical significance reached in the 250 mg PBT-2 dose arm compared to placebo (p=0.006). This effect was dose related (p=0.02). Cognitive improvement, as measured via the Neuropsychological Test Battery (NTB), was also observed. After twelve weeks, statistically significant improvement was evident in two of the four Executive Function NTB tests: the Category Fluency Test (p=0.028) and the Trail Making Test part B for the PBT-2 (250 mg) group over placebo (p=0.005). Based on the results Prana plans to move forward with the development of PBT-2..
February 11, 2008
BioLine RX reported positive results from a phase IIa trial of BL-1020 for the treatment of schizophrenia. This open label, 6-week study enrolled 36 treatment refractory and hospitalized subjects. The subjects were started on 32mg (20mg free base) of BL-1020 and received increasing dosages over the first 7 days in order to reach the maximum dose of 64 mg (40mg free base). The primary endpoints were reached in the BL-1020 arm, with significant improvements from baseline in the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression of Severity and Improvement (CGI-S, CGI-I). There was a statistically significant improvement on the PANSS total (baseline=84.9; day 42=63.8), and the positive (baseline=22.3; day 42=15.1) negative (baseline=20.9; day 42=16.6) and general psychopathology subscales (baseline=42.4; day 42=32.1) (p less than 0.001). In addition, more than 80% of the subjects treated with BL-1020 showed a clinically significant improvement as reflected by the CGI-S and CGI-I. Treatment was well tolerated, with no unexpected adverse events. Based on the results, BioLine RX is planning to commence a phase IIb trial during the second quarter of 2008.
Neuro-Hitech released mixed results from the double blind portion of a phase II trial of Huperzine A for the treatment of Alzheimers disease. This multi-center, randomized, double-blind, placebo-controlled trial enrolled two hundred subjects with mid-to-moderate Alzheimers disease. The subjects were administered either 200 or 400 micrograms of Huperzine A or placebo, orally twice a day for sixteen weeks. Approximately half the subjects received concomitant treatment with Namenda, an approved treatment for Alzheimers. The primary endpoint was the mean change on AD Assessment Scale- Cognitive (ADAS-Cog) scores after sixteen weeks. Results showed that there was no statistical difference in the mean ADAS-Cog scores for the Huperzine A 200 micrograms arm compared to placebo (p=0.81). However, the higher dose tested, 400 micrograms, showed cognitive enhancement on the ADAS-Cog versus placebo; the maximum cognitive improvement was observed at week eleven of treatment (p=0.001). Over sixteen weeks the Huperzine A 400 micrograms arm improved cognition compared to placebo (p=0.03) and there was a trend to cognitive improvement over placebo at week 16 (p=0.069). There was no statistical difference between placebo and either 200 or 400 micrograms of Huperzine A in any of the secondary endpoints, including clinical global impression of change (ADCS-CGIC) and the Neuropsychiatric Inventory (NPI). Treatment was safe and well tolerated, with an adverse event profile similar to placebo. Neuro-Hitech plans to move forward with the development of Huperzine A.
Penwest issued mixed results from a phase IIa trial of nalbuphine ER for the treatment of moderate chronic pain. This randomized, double-blind, placebo controlled study enrolled one hundred and thirty eight subjects with chronic pain secondary to osteoarthritis of the knee or hip. The subjects received the lowest dose of nalbuphine ER for week one, increased to a mid-dose level for week two, and increased to the highest dose studied for week three. The primary endpoint was the Sum of Pain Intensity Differences between baseline and day twenty one. Nalbuphine ER did not meet this endpoint, which was possibly due to patient dropouts in the first week of dosing. The drug did, however, achieve a number of the secondary endpoints compared to placebo, including statistical significance in the Global Assessment of Pain Control (p=0.006) and the Integrated Assessment of Pain Intensity and Rescue Medication Use (p=0.009). Nalbuphine ER was well tolerated, with no reports of drug related serious adverse events. Based on the results, a phase IIb trial is planned for later in 2008.
January 7, 2008
Epix issued positive results from a phase IIa trial of PRX-03140 for the treatment of Alzheimers disease. This randomized, double-blind, multiple ascending dose trial enrolled eighty subjects with mild Alzheimer's disease, all of whom were on a stable dose of donepezil (10 mg). The subjects were evaluated on PRX-03140 monotherapy (across three dose arms of ten subjects each: 50 mg once-daily, 150 mg once-daily and placebo, administered orally once a day for 14 days) or in a placebo-controlled combination with 10 mg donepezil (across five dose arms of ten subjects each: PRX-03140 at 5, 25, 50, 100 and 200 mg with donepezil 10 mg once-daily). The primary endpoint was reached with statistical significance in the 150 mg PRX-0140 arm, with a mean 5.7 point improvement on the Disease Assessment Scale cognitive subscale (ADAS-cog) versus a 0.2 point worsening for the subjects receiving placebo (p= 0.005). The subjects in the 50 mg PRX-03140 arm achieved a 1.1 score improvement on the ADAS-cog scale. The 150 mg PRX-03140 arm also showed statistically significant improvement versus the 50 mg (monotherapy) PRX-03140 and placebo arms (p=0.02). The onset of this benefit was observed within two weeks. PRX-03140 was determined to be safe and well tolerated across all dose groups. Based on the results. Epix plans to continue with the development of PRX-03140.
November 19, 2007
Memory Pharmaceuticals reported positive results from a phase IIa trial of MEM 3454 for the treatment of Alzheimers disease. This randomized, double-blind, placebo-controlled trial enrolled eighty subjects with mild to moderate Alzheimer's, in the US. Subjects received MEM 3454 (5 mg, 15 mg or 50 mg) or placebo once daily for eight weeks. The primary endpoint was to assess the efficacy of MEM3454 using the Quality of Episodic Secondary Memory (QESM) factor score from the Cognitive Drug Research (CDR) battery. The CDR battery was administered at baseline and on six days during the treatment period, at four time points each day (pre-dosing and two, four and eight hours post-dosing). For the eight hour post-dose time points, subjects receiving 5 mg and 15 mg of MEM 3454 demonstrated a statistically significant effect on the QESM compared to placebo (p=0.023 and p=0.050, respectively). On secondary CDR battery measures, for all time points combined, the trial showed that the 5 mg and 15 mg doses achieved statistically significant positive results on Quality of Working Memory (p=0.031 and p=0.047). The 15 mg group also demonstrated trends to efficacy on Speed of Memory (p=0.080). In addition, the 15 mg group showed numeric improvements favoring treatment over placebo on another secondary endpoint, Alzheimer's Disease Assessment Scale -- cognitive subscale (ADAS-Cog). Based on the results, Memory plans to continue with the development of MEM 2454 for this indication.
October 22, 2007
Memory Pharmaceuticals reported negative results from a phase IIa trial of MEM1003 for the treatment of Alzheimers disease (AD). This randomized, double-blind, placebo-controlled study enrolled 183 subjects with mild to moderate AD in the US. Enrollment included a subgroup of subjects on stable doses of cholinesterase inhibitors and a subgroup on MEM1003 monotherapy. During the double-blind phase, subjects received one of two doses of the drug (30 mg or 90 mg) or placebo twice daily for 12 weeks. This was followed by a 4 week single blind placebo treatment period. The primary efficacy endpoint for the trial was change in 12-week score on the Alzheimer's Disease Assessment Scale -- Cognitive subscale (ADAS-cog). The primary endpoint was not reached due to a large placebo response in the subgroup of monotherapy subjects. In the subgroup of subjects receiving cholinesterase inhibitors, the change in ADAS-cog favored treatment over placebo, although this difference was not statistically significant. This sub-group also reached all secondary endpoints. Treatment was well tolerated, with adverse events similar across all treatment arms. Based on the results, Memory plans to continue with the development of MEM1003 for this population.
September 3, 2007
Accera announced positive results from a phase II trial of Ketasyn for the treatment of age-associated memory impairment (AAMI). This US based, randomized, double-blind, placebo-controlled, parallel trial enrolled 159 subjects with a mean age of 65 who were diagnosed with AAMI. The subjects received Ketasyn or placebo for 90 days followed by a two-week washout period. They subsequently underwent genomic testing for variations in coding regions of genes known to influence memory and cognition, including the apolipoprotein E4 gene (APOE4). On days 0, 30, 60, 90 and 104, the subjects were evaluated through a battery of neuropsychometric tests to measure cognition and memory. Results showed subjects taking Ketasyn performed significantly better on the First-Last Name Association (FLN) test and on the Name-Face Recognition (NFA) test at day 90 (p=0.042 and p=0.0217, respectively). The subjects who did not have the APOE4 genotype, APOE4(-), showed a further significant treatment effect with Ketasyn compared to placebo in FLN at day 90 (p=0.012). The subjects who were APOE4(+) showed no difference between Ketasyn and placebo for FLN scores at Day 90 (p=0.4639). Treatment was well tolerated, with adverse events similar between the active and placebo groups. Based on the results, Accera plans to initiate a phase III trial in early 2008.
Neurochem reported negative results from a phase III trial of Alzhemed for the treatment of Alzheimers disease (AD). This randomized, double-blind, placebo-controlled, three-armed and parallel-designed, 18-month trial enrolled 1,052 subjects with mild-to-moderate AD in the United States and Canada. Subjects received either placebo or one of two doses of Alzhemed (100 mg or 150 mg) twice daily. Treatment with Alzehemed did not demonstrate a statistically significant improvement over placebo with respect to the primary endpoints of efficacy and disease modification. However, a statistically significant difference was observed in hippocampal volume between the Alzehemed and placebo treatment groups. Neurochem plans to use this data to modify the study design of an ongoing European phase III clinical trial.
Transition and Elan released positive results from several phase I trials of ELND-005/AZD-103 for the treatment of Alzheimers disease. These single and multiple ascending dose trials enrolled a total of 110 healthy subjects. Treatment was safe and well-tolerated at all doses and dosing regimens examined, with no reported adverse events. ELND-005/AZD-103 was also shown to be orally bioavailable, cross the blood-brain barrier and achieve levels in the human brain and CSF that were shown to be effective in preclinical animal models for Alzheimer's disease. Based on the results, Transition and Elan plan to commence phase II trials by the end of 2007 or early 2008.
May 14, 2007
Ceregene issued positive interim results from a phase I trial of CERE-110 for the treatment of Alzheimer's disease (AD). This single-site, open-label trial enrolled 6 subjects with mild-to-moderate AD. All subjects underwent stereotactic neurosurgery to deliver CERE-110 into the Nucleus Basalis of Meynert region of the brain. They subsequently underwent cognitive testing and PET scans at baseline, 6 and 12 months. Results suggested a reduction in the rate of cognitive decline. Increases in brain metabolism were observed in several cortical regions at six months (p<0.05) and12 months (p<0.05). Treatment was well tolerated. Based on the results Ceregene plans to initiate a phase II trial in 2008.
Insmed announced positive preliminary results from a phase II trial of iPlex for the treatment of myotonic muscular dystrophy (DM1). Six subjects have completed treatment to date in this open-label trial. These subjects received iplex up to 1 mg/kg/day for six months. Treatment was safe and well tolerated, with no reported adverse events. Improvements in cholesterol and triglycerides, as well as in gastrointestinal function, endurance and cognitive function were observed. In addition, 5 out of 6 subjects showed an improvement in lean muscle mass. The second cohort of subjects is currently being treated at an iPlex dose of 2 mg/kg/day, for six months.
PTC reported positive interim results from a phase II trial of PTC124 for the treatment of Duchenne muscular dystrophy (DMD). This open-label, dose-comparison, single-group-assignment study enrolled pediatric male subjects with nonsense-mutation-mediated DMD. Subjects received one of three doses of PTC124 for 28 days. The primary endpoint was the proportion of subjects with an increase in dystrophin expression in muscle during the treatment duration. Reported results are from the first two cohorts, 26 total subjects, who received the low and medium dose levels. Overall, 67% of subjects treated at the lower dose level and 50% of subjects treated at the medium dose level demonstrated an increase in the expression of dystrophin post-treatment. In addition, statistically significant improvements in concentrations of muscle-derived creatine kinase levels in the blood were observed during PTC124 treatment. Accrual and analysis of the third cohort is currently underway.
October 2, 2006
Acorda released positive results from a phase III trial of Fampridine-SR for the treatment of walking in subjects with multiple sclerosis. This double-blind, placebo-controlled trial enrolled 301 subjects in the US and Canada who had a definite diagnosis of MS and some degree of walking disability. Subjects were randomized receive Fampridine-SR (n=229) or placebo (n=72), for 14 weeks. Treatment was well tolerated with falls and urinary tract infections the most commonly reported adverse events. Efficacy data revealed that the trial met the primary endpoint of improvement in walking speed, as measured by the Timed 25-Foot Walk, with 34.8% of the Fampridine-SR group showing improvement versus 8.3% of the placebo group (p less than 0.001). This improvement was maintained throughout the length of the treatment. In addition, after 14 weeks the average increase in walking speed compared to baseline was 25.2% for the treated group versus 4.7% for the placebo group. Based on this data Acorda plans to move Fampridine-SR into further development.
CytRx issued positive results from a phase IIa trial of arimoclomol for the treatment of amyotrophic lateral sclerosis (ALS). This multi-center, double-blind, placebo-controlled trial enrolled 84 subjects with ALS, who received arimoclomol, or placebo, in one of three dose levels (25 mg, 50 mg or 100 mg) three times daily for 12 weeks. They were then studied for an additional four weeks without treatment. Treatment was shown to be safe and well tolerated across all dose ranges, with no statistically significant adverse events reported. Pharmacokinetic data indicated that arimoclomol effectively entered the cerebral spinal fluid. The amount of the drug in the cerebral spinal fluid was similar to the amount in the blood and increased as the dose increased. Based on these results a phase IIb efficacy trial, using arimoclomol at the highest dose level, is planned for H1 2007.
Medivation issued positive results from a phase II trial of Dimebon for the treatment of Alzheimer's disease. This six-month randomized, double-blinded, placebo-controlled trial enrolled 183 subjects at 11 sites in Russia, who received treatment for 26 weeks. Treatment was well tolerated with the most commonly reported adverse event dry mouth. Efficacy data revealed that all endpoints were met. Subjects receiving Dimebon demonstrated a statistically significant improvement on the study's primary efficacy endpoint, the Alzheimer's Disease Assessment Scale-cognition, with a 4.0 point improvement in the mean change from baseline to week 26 as compared to placebo (p less than 0.0001). The secondary key endpoint, mean change in Clinical Global Impression of Change, was met as well, with a 0.6 point improvement from baseline to week 26 as compared to placebo (p less than 0.0001). Additional phase II trials are ongoing, with results expected in Q2 2007.
August 14, 2006
Evotec AG announced positive results from a phase I trial of EVT 101, for the treatment of Alzheimer's disease and neuropathic pain. This trial enrolled 90 healthy, young and elderly subjects who received EVT101 in single or multiple ascending oral doses. Tolerability profiles were positive, with no significant adverse events reported. Pharmacokinetic data revealed a positive profile, with good drug absorption and a half-life of 11 hours, a time frame is consistent with a once or twice daily oral dosing regimen.
Vectura Group issued positive results from a phase II study of VR004 for the treatment of "off episodes" related to Parkinson's disease. This randomized, double-blind, placebo-controlled, four parallel group, ascending dose study enrolled 24 subjects. Subjects were taken off their conventional treatment to induce an "off" episode, than given one or two fine particle doses of VR004 or placebo at 200 mcg, 300 mcg, 500 mcg, 750 mcg, 800 mcg or 1,200 mcg. Safety data was positive, with no serious adverse events reported. Pharmacokinetic data demonstrated that maximum VR004 plasma concentrations occurred 1-3 minutes after dose inhalation. Efficacy data revealed that the median onset of response was 10 minutes and the median duration of response after inhalation was 25 minutes. Based on these results, Vectura planned to further advance VR1004 in future clinical trials.
July 24, 2006
Myriad Genetics has issued positive results of a phase II follow-on trial of Flurizan, for the treatment of Alzheimer's disease (AD), at the 10th International Conference on Alzheimer's Disease and Related Disorders, in Madrid, Spain. This open-label extension study enrolled subjects from an earlier 12-month trial or the drug. Subjects received either 400 mg or 800 mg Flurizan twice daily for an additional 12 months. Trial data indicated that subjects receiving the drug during both the original trial and follow-on trials demonstrated continued clinical benefit, with a 72% on the CDR-sb test (p=0.0005), and a 67% effect size on the ADCS-ADL scale (p=0.015). Further benefit was noted in improving the rate of cognitive decline, with a 54% effect size on the ADAS-cog scale. Finally, subjects who received the 800 mg dose for the full 24 months showed slower cognitive decline than subjects who received placebo for the first 12 months; subjects randomized from placebo to 800 mg showed less decline in some measures (ADAS-cog and CDR-sb) than those randomized from placebo to 400 mg.
May 15, 2006
Prana Biotechnology announced pooled results from their phase I development program for PBT2 for the treatment of Alzheimer's disease (AD). These trials enrolled 55 young male volunteers and 32 older male and female volunteers; they were designed to investigate the safety, tolerability and pharmacokinetics of single and multiple oral doses of the drug. Preliminary data yielded a positive tolerability profile for doses up to 800 mg, with no significant differences in rates of adverse events (most common events included headache, gastrointestinal disturbance and somnolence). Maximum tolerated dose was not reached. Pharmacokinetic data indicated a rapid absorption profile, with peak plasma concentrations achieved within 3 hours of administration, a linear absorption profile following single doses of the drug, and little drug accumulation in multiple-dose regimens.
March 20, 2006
Avicena has issued positive results of a phase II trial of PD-02, for the treatment of Parkinson's disease (PD), in the journal Neurology. Trial data indicted that both PD-02 and minocycline had potential in inhibiting disease progression, with the rate of progression for both drugs below the threshold of futility on the Unified Parkinson's Disease Rating Scale (UPDRS). In addition, treatment with PD-02 was found to be safe and generally well tolerated. This randomized, double-blind, multi-center study enrolled 200 treatment naïve patients with early stage PD, who received 10 g PD-02, 200 mg of the approved antibiotic minocycline, or placebo daily for 12 months. Based on these results, Avicena initiated discussion of potential designs for phase III trials of PD-02.
Myriad Genetics reported positive results of a phase II follow-on trial of Flurizan, for the treatment of Alzheimer's disease (AD). Results from the study indicated that the drug produced a 52% effect size on the ADCS-ADL diagnostic scale (a measure of activities of daily living), compared to projected scores for placebo at 21 months (p=0.029). Efficacy was also noted on the CDR-sb diagnostic scale, measuring global function, with a 75% effect size vs. projected values for placebo (p=0.007). A non-significant 60% effect size was noted in rate of cognitive decline, as measured on the ADAS-cog diagnostic scale (p=0.096). This double-blinded extension study enrolled patients from an earlier 12-month phase II study in Canada; subjects receiving the drug in the earlier trial maintained their regimen, and subjects previously on placebo were randomized to receive 400 mg or 800 mg twice daily.
February 20, 2006
Axonyx has issued positive results of a phase I trial of phenserine, for the treatment of Alzheimer's disease (AD). The drug was shown to significantly reduce plasma beta-amyloid 1-42 levels two hours post dosing at 35 days (from 102.2 pg/ml at baseline to 81.3 pg/ml; p<0.01). The decreases in beta amyloid levels coincided with maximum plasma phenserine concentrations. No unexpected safety concerns were raised. This open label multiple dose study enrolled 12 healthy volunteers, who received 10 mg phenserine twice daily for 28 days, followed by 15 mg twice daily for 7 days.
January 30, 2006
Avicena announced results of a phase I/II trial of HD-02, for the treatment of Huntington's disease (HD), in the journal Neurology. Results from the study indicated that serum levels of 8-hydroxy-2'-deoxyguanosine (8OH2'dG), an HD disease biomarker, were significantly reduced in patients receiving the drug. Safety and tolerability results were generally positive, and after drug-free washout, serum creatine levels had returned to baseline. This multi-center, double-blind, placebo-controlled study enrolled 64 patients, who were randomized to receive 8 g HD-02 or placebo daily for 16 weeks, followed by an 8 week drug washout.
Axonyx has announced positive results of a phase I trial of Posiphen for the prevention of Alzheimer's disease (AD) progression. The drug yielded a positive safety profile, with no serious adverse events reported and a good overall tolerability profile. Peak serum drug concentrations exceeded those predicted in animal models to be efficacious in affecting beta-amyloid metabolism. This double-blind, placebo controlled study enrolled 60 healthy volunteers, who received 1 of 5 single doses of Posiphen (10 mg, 20 mg, 40 mg, 80 mg or 160 mg) or placebo.
Javelin Pharmaceuticals issued preliminary results of a phase IIb trial of Dyloject (diclofenac sodium injection) for the treatment of pain. Trial data met their primary efficacy endpoint, producing significant, linear-dose-response pain relief over 6 hours, as measured on the Visual Analog Scale. This response was superior to placebo and non inferior to approved therapy with Ketorolac. The drug experienced superior onset of pain relief after 5 minutes, compared to Ketorolac, on both the Visual Analog and Categorical scales. This randomized study enrolled 353 patients with moderate-to-severe post-surgical pain, who received single administrations of 1 of 5 doses of the drug (up to 75 mg), an approved regimen of IV Ketorolac (30 mg), or placebo.
November 14, 2005
Prana Biotechnology has announced positive results of a phase I trial of their investigational metal-ion chelator PBT-2 for the treatment of Alzheimer's disease. Results from the study indicated a positive overall tolerability profile, with little difference in rates of adverse events between PBT2 and placebo. Pharmacokinetic data yielded a linear, dose-related absorption profile, and the drug crossed the blood-brain barrier with 20 times greater efficiency than their earlier investigational compound PBT1. This double blind, placebo-controlled single dose escalation study enrolled 55 healthy volunteers at a single site in Utrecht in The Netherlands. These data were seen to support an ongoing multi-dose-escalation study of the drug, in preparation for phase II trials.
October 3, 2005
Myriad Genetics announced positive results of a phase II follow-up trial of Flurizan, for the treatment of Alzheimer's disease (AD). Trial data from the 3-month follow-up period indicated that subjects receiving high dose Flurizan did not experience symptomatic disease progression: over the first 12 months of treatment (the start of the follow-up), subjects experienced a average decline of 2.8 points on the ADAS-cog diagnostic scale; at month 15, at the end of the follow-up, average ADAS-cog decline relative to baseline was 2.7 points, an improvement of 0.1 points. Symptom severity score on the CDR-sb scale yielded a rate of decline in score over months the extension period (months 12-15) was 0.03 points per month, compared to 0.11 points-per-month during the original study (months 0-12), indicating potentially slowed disease progression. This 3-month open-label extension study enrolled 81% of patients from the original trial; patients who had received Flurizan in the original 12-month study continued to receive their original dose, and subjects who received placebo were switched to 400 mg or 800 mg twice daily.
September 26, 2005
Axonyx reported negative top-line results of a pair of phase III trials, dubbed AX-CL-09 and AX-CL-10, of phenserine, for the treatment of Alzheimer's disease. Enrollment in these trials had been previously curtailed following negative results of an earlier study, AX-CL-06. Trial data failed to demonstrate efficacy in improving performance on either the ADAS cog or CIBIC+ diagnostic scales at 12 weeks, compare to placebo. No safety or tolerability concerns were raised. These identical-design, double-blind, placebo-controlled studies enrolled 255 mild-to-moderate Alzheimer's patients (of an originally planned 900) across 72 sites in 10 countries, who received one of two doses of phenserine or placebo for 12 weeks (of an originally planned 26).
May 9, 2005
Myriad Genetics reported mixed preliminary results of a phase II trial of Flurizan, for the treatment of mild-to-moderate Alzheimer's disease (AD). Trial data from the overall treatment group failed to meet the primary efficacy endpoint, a reduction in rate of performance decline on the ADCS-ADL, CDR-sb, and ADAS-cog diagnostic scales vs. placebo, though positive trends were noted at in the higher dosing regimen (44%, 41% and 29% reductions, respectively; p>0.05 for all measures). However, analysis of the sub-group with "mild" overall disease severity (n= 128) revealed that subjects in this group who achieved the highest drug plasma concentrations did achieve significant reduction in the rate decline on ADCS-ADL (67% reduction vs. placebo; p=0.017) and CDR-sb (54% reduction vs. placebo; p=0.034), and a trend towards rate reduction on ADAS-cog (30% reduction vs. placebo; p>0.05). This randomized, double-blind, placebo-controlled study enrolled 207 patients with mild-to-moderate AD across 30 sites in the United Kingdom and Canada. Subjects received one of two doses of Flurizan (400 mg or 800 mg) or placebo twice daily for 12 months. Based on these results, Myriad announced plans to conduct a phase II trial of the drug using the 800 mg twice daily dose, with a focus on patients with mild AD symptoms.
May 2, 2005
Ceregene reported the results of a phase I trial of human nerve growth factor (NGF), delivered via NGF-expressing modified fibroblast implantation into the forebrain, for the treatment of Alzheimer's disease. Results from the study indicated that the treatment was well tolerated, with no long term adverse events reported. Serial PET scanning yielded significant increases in cortical 18-fluorodeoxyglucose uptake following treatment (p<0.05), and evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subcomponent suggested mitigation of rate of cognitive decline. Autopsy results from one patient suggested robust neuronal growth following treatment. This unblended study performed NGF fibroblast implantation on 6 patients with mild Alzheimer's disease, who were followed for indications of safety and efficacy for 22 months.
Neurochem has reported positive interim results of a phase III trial of Alzhemed, their investigational amyloid beta fibrillogenesis inhibitor for the treatment of Alzheimer's disease (AD). Preliminary safety 12-week results from the first 562 patients enrolled yielded no indication of serious adverse events or tolerability concerns, and prompted the trial's Independent Safety Review Board to recommend that the study continue without modification. This multicenter, randomized, double-blind, placebo- controlled, three-armed, parallel-design study has enrolled 950 patients with AD across 68 sites in North America, who were to receive treatment for 18 months. The company announced plans to initiate a phase III trial of Alzhemed in Europe in the fall of 2005.
Neurologix presented positive interim results of a phase I trial of GAD (glutamic acid decarboxylase) gene therapy for the treatment of Parkinson's disease at the 73rd annual meeting of the American Association of Neurological Surgeons in New Orleans. Preliminary data from the first 4-patient dosing cohort in the ongoing study have met their primary safety endpoints, with no serious adverse events or tolerability concerns raised. This open-label dose- escalation study enrolled 12 patients with advanced Parkinson's disease at the The New York Presbyterian Hospital/Weill Medical College of Cornell University. Subjects were randomized to receive one of three single doses of the therapy delivered via stereotactic neurosurgically- implanted microcatheter. The company announced plans to initiate efficacy evaluation of the drug in the near future, based upon the positive safety profile presented in this study.
NovaDel has issued positive results of a pilot study of a lingual spray formulation of the approved anxiolytic alprazolam, marketed by Pfizer as Xanax. Pharmacokinetic data indicated that the lingual spray produced a more rapid rate of absorption than the approved formulation, with a time to therapeutic plasma concentration of 15 minutes, versus 35 minutes for the oral tablet. Further, the drug showed higher percentage of maximum concentration (Cmax) at earlier time- points, including a statistically significant results at 12 minutes: 38.5% for the spray vs. 18.8% for the tablet (p<0.05). Preliminary efficacy was also demonstrated, with all lingual spray groups self-rating higher on relaxation and drowsiness parameters at 30 minutes. This open- label study enrolled 9 healthy volunteers, who each received 3 ascending doses of the lingual spray (0.25mg, 0.75mg, and 1mg) and 3 doses (0.5 mg) of the oral tablets. NovaDel announced plans to meet with the FDA to discuss a broader clinical development program for the drug.
March 21, 2005
Axonyx announced positive interim results of a phase IIb trial of Phenserine tartrate, for the treatment of mild-to-moderate Alzheimer's disease. These data were also presented at the 7th International Conference on Alzheimer's and Parkinson's disease in Sorrento, Italy. Study results yielded evidence of efficacy in the primary endpoint, producing a reduction in cerebrospinal fluid beta-amyloid concentrations at both dose levels (low dose:-1.16 pg/ml, high dose: -35.65 pg/ml) compared to an increase in concentrations among subjects receiving placebo (+22.38 pg/ml). In the interim data analysis, neither reduction achieved statistical significance, but the reduction observed for the high dose group was sufficiently large to warrant continued enrollment and treatment in the trial. This double-blind placebo-controlled trial had enrolled 37 subjects to date, who were randomized to receive one of two doses of the drug (10 mg, n=11; or 15 mg, n=19) or placebo (n=7) twice daily for 6 months. The company announced that trial data warranted continued enrollment in the 15 mg dose group, which was expected to be completed in the second quarter of 2005, with final results expected before the end of the year.
February 14, 2005
Axonyx announced top-line results of their first phase III trial of phenserine, their acetylcholinesterase inhibitor under investigation for the treatment of mild-to-moderate Alzheimer’s disease (AD). Trial data indicated that the neither trial dose of the drug met the primary endpoint, improvement in score on the ADAS-cog and CIBIC diagnostic scales, vs. placebo after 26 weeks of treatment. Non-significant trends towards improvement were noted in both metrics at both dose regimens, and no serious safety or tolerability concerns were raised. This double-blind, placebo-controlled study enrolled 384 subjects across 16 sites in Spain, the United Kingdom, Croatia, and Austria. Subjects were randomized to receive one of two doses of phenserine (10mg or 15mg) or placebo twice daily for 6 months. Axonyx announced that the planned interim analysis of their ongoing phase II b trials of the drug, investigating phenserine’s ability to lower levels of beta-amyloid precursor protein and beta-amyloid in the plasma and cerebrospinal fluid (CSF), would not be affected by these results.
Cephalon has reported positive combined results from four phase III trials of Nuvigil (armodafinil) for the treatment of excessive sleepiness associated with narcolepsy (1 study), shift work sleep disorder (1 study) or obstructive sleep apnea/hypopnea syndrome (2 studies). Compiled data demonstrated significant efficacy in improving measures of objective sleep latency, including the Maintenance of Wakefulness Test and the Multiple Sleep Latency Test, and in the physician rating of Clinical Global Impression-Change, vs. placebo (p<0.05). The drug was also shown to promote wakefulness late in the day when administered in the morning, confirming a long duration of action. All 4 trials were 12-week, double-blind, randomized, placebo-controlled studies, which enrolled a combined total of roughly 1,000 patients. Subjects received one of two doses of the drug (150 or 250 mg) or placebo once daily. Cephalon announced that these results were in line with their intention to submit and NDA for the drug before the end of Q1 2005.
Repligen announced preliminary results of a phase II trial of secretin, for the treatment of refractory schizophrenia. Data from the study yielded no significant improvements in symptom severity scores on either the Clinical Global Impression (CGI) or the Positive And Negative Syndrome Scale (PANSS), which were assessed at baseline and 6 times during the study. Responders on the CGI scale were noted in both the low dose (n=3, 20% response rate) and high dose (n=4, 29% response rate) secretin group and in the placebo group (n=2, 13% response rate), but the difference between these rates was also non-significant, possibly due to the small cohort size. A non-significant trend towards improvement was seen in a sub-section analysis of the PANSS dysphoric mood scale (anxiety, tension, etc.) in the secretin group (p=0.06), and several clinical investigators were reported to have noted transient changes in the social interaction at the time of the treatment, though these responses were not quantified. This double-blind trial enrolled 44 subjects, who received one of two doses of secretin (2 CU/kg, n=15; or 5 CU/kg, n=14) or placebo (n=15) in 4 intravenous doses over 2 weeks. The company announced that they were preparing a follow-up study to statistically measure the transient changes in mood noted by investigators.
January 24, 2005
GW Pharmaceuticals has announced preliminary results of a phase III trial of Sativex (tetrahydrocannabinol/cannabidiol), their fixed-dose direct cannabinoid-receptor agonist, for the treatment of severe cancer pain. GW is also pursing development of the drug for multiple sclerosis and neuropathy/neuropathic pain in Canada and the UK; the drug is not currently in development in US markets. Study results indicated that the drug met its primary endpoint, with a significant improvement in patient-reported experience of pain (p=0.014), vs. placebo. This included a significantly greater portion of subjects receiving Sativex reporting a 30% or greater reduction in pain, vs. placebo (40% of subjects receiving Sativex; p=0.024). Furthermore, the study indicated that subjects who received only tetrahydrocannabinol did not show a significant improvement in ratings of pain vs. placebo (p=0.24), confirming Sativex’s fixed-dose combination. This multi centre double-blind, placebo-controlled parallel group study randomized 117 patients experiencing severe cancer pain unresponsive to opioid therapy to receive Sativex, tetrahydrocannabinol alone, or placebo at a 1:1:1 ratio. The company announced that it would review any additional steps needed for regulatory submission, including the design of an additional confirmatory phase III trial.
Phytopharm issued positive interim data from a ongoing phase II proof-of-principle study of their drug Cogane (PYM50028), for the treatment of Alzheimer’s disease. The interim safety review yielded no serious safety concerns, based on data from the first 60 subjects. Furthermore, independent review estimated a total necessary enrollment of between 200 and 238 subjects (the secondary purpose of the interim review). This randomized, double-blind, placebo-controlled study was designed to evaluate the safety, efficacy and pharmacokinetic profile of PYM50028 after once daily oral administration for 12 weeks to patients with Alzheimer's disease. Phytopharm announced plans to submit the necessary applications to expand the trial size, based on these results.
October 18, 2004
Hemispherx Biopharma presented expanded data from their phase III study of Ampligen, for the treatment of chronic fatigue syndrome (CFS), at the 7th International Conference for CFS in Madison, Wisconsin. The data, which covered subjects in the intent-to-treat population, demonstrated that subjects receiving the drug experienced symptom relief, with a significant improvement in treadmill exercise tolerance (p=0.037) compared with placebo; this improvement was more than twice the level required to achieve medical significance. Secondary safety endpoints were also satisfied, with no significant difference in serious adverse events, missed dosages or dropouts between Ampligen and placebo groups. The double-blind, placebo-controlled study randomized 234 patients with severe/debilitating CFS across 12 US sites to receive twice weekly doses of either 400 mg. Ampligen or placebo for 40 weeks. Following these results, Hemispherx announced that they were preparing for the filing of a NDA for Ampligen; if approved, the drug would be the first drug indicated for the treatment of CFS.
NPS Pharmaceuticals reported negative results of a proof-of-concept clinical trial of NPS 1776 (isovaleramide), for the treatment of acute migraine headaches. The study failed to meet its primary endpoint, a significant reduction in acute headache pain two hours after administration compared with placebo. NPS attributed this failure to a higher-than expected placebo effect: 56% of subjects receiving placebo achieved primary response, compared with 60% of subjects receiving the higher dose of the drug and 64% of subjects receiving the lower dose. Secondary safety endpoints were met, with no serious adverse events and no minor events occurring more frequently with the drug than placebo. The double-blind, placebo-controlled study randomized 189 patients with moderate-to-severe migraine pain to receive one of two doses of the drug or placebo. NPS announced that they planned to continue investigation of the drug in other indications, but did not report the intention to continue pursuing the drug for migraine.
Prana Biotechnology announced the results of an open-label extension of a phase II study of PBT-1 (clioquinol), a copper-zinc attenuator/amyloid-beta aggregation inhibitor for the treatment of Alzheimer’s disease (AD). Data from the study confirmed the positive results achieved in the original trial: subjects experienced a mean decline of 8 points on the ADAS-cog scale, a standardized diagnostic scale for cognitive performance in AD, compared with a literature-established expected decline of 18 points. The drug was also found to be safe and well tolerated, with no significant increase in adverse events over untreated subjects. This 48-week open-label extension to the 36-week double-blind, placebo-controlled phase II CQAD study enrolled 18 of the original participants, 9 of whom completed treatment. Prana announced that they were continuing to evaluate the study data, in preparation for advancing the drug into further clinical studies.
September 7, 2004
Forest Laboratories has reported negative preliminary results of their phase III trial of neramexane, for the treatment of Alzheimer’s disease. The study found that the drug did not produce significant evidence of efficacy: subjects receiving neramexane adjunct to standard acetylcholinesterase inhibitor therapy showed no significant improvement in cognition or function, as measured on two standard diagnostic scales. The drug also failed to meet its secondary endpoint, an improvement in clinician perception of disease severity. No safety issues were raised. The trial enrolled 415 moderate to severe Alzheimer’s patients on an outpatient basis. Forest announced that they planned to continue trials of neramexane as a monotherapy for Alzheimer’s.<
July 26, 2004
Myriad Genetics announced results of their phase I study of their Alzheimer’s candidate Flurizan (R-flurbiprofen). Results demonstrated that the drug was safe and well tolerated, with no serious adverse events, no significant difference in minor adverse events between subjects receiving Flurizan and placebo. In addition, there were no dropouts due to adverse events in either the Flurizan or placebo groups. The double blind, dose escalating, placebo controlled study randomized 48 healthy elderly subjects between the ages of 55 and 80, who received a daily regimen of one of three doses of Flurizan or placebo for 21 days.
April 26, 2004
Prana Biotechnology reported positive results from an extended phase II trial investigating PBT-1 (clioquinol), a metal protein attenuating compound for the treatment of Alzheimer’s disease. Results showed that PBT-1 slowed the decline in cognitive function associated with Alzheimer's disease compared with historically normal levels of decline. The extension study enrolled nine subjects and was conducted over 48 weeks following the original trial of 36 weeks. Results were reported at the 8th International Springfield/Montreal Symposium on Advances in Alzheimer's Disease.
April 19, 2004
Neurochem reported positive interim results from a phase II trial investigating Alzhemed, an oral small molecule for the treatment of Alzheimer’s disease (AD). Results showed that 82% of subjects had stabilized or improved cognitive function tests after 16 months of treatment with Alzhemed. Data showed mild AD subjects showed a change from baseline in their average ADAS-cog score of -0.09 points. Results were from the three-month randomized trial and an additional 13 months open-label extension study (OLPES) enrolling a total of 30 subjects. Data was reported at the 8th International Montreal/Springfield Symposium on Advances in Alzheimer Therapy. The company expects to initiate a phase III trial with Alzhemed in the first half of 2004.
November 24, 2003
Neurochem reported positive results from phase II trial investigating Alzhemed, a small sulfonated molecule for the treatment of Alzheimer’s disease. Data demonstrated that patients with mild AD showed the greatest benefits from Alzhemed compared to patients with moderate AD. Results showed that the overall cognitive function improved by 59% when compared to the decline exhibited by historical, untreated control patient groups after 9 months of follow-up. Subjects with mild AD demonstrated an average of -3.5 points of improvement in their cognitive function after 9 months. Cognitive function was measured by the Alzheimer’s Disease Assessment Scale (ADAS-cog). The open-label, extension study enrolled 33 subjects with mild to moderate AD.
September 2, 2003
Novartis Pharmaceuticals reported positive results from a phase IV trial investigating Exelon (rivastigmine tartrate), for the treatment of Alzheimer's disease symptoms. Data demonstrated that the drug may reduce certain behavioral symptoms associated with Alzheimer's disease, such as delusions and hallucinations. The first analysis evaluated the effects of Exelon on neuropsychiatric and behavioral disturbances. Results showed more than half (59%) of Exelon-treated patients with at least one behavioral symptom at baseline showed improvement on the NPI-NH scale for psychiatric and behavioral disturbance, a mean improvement of 64%. Treatment demonstrated an improvement in subjects with that specific symptom: delusions, hallucinations, agitation, apathy/indifference, irritability, aberrant motor behavior, night-time behavior, and appetite/eating change. The 26-week, prospective open-label study enrolled 173 nursing home residents with Alzheimer's. Results were presented at the 11th Annual Congress of the International Psychogeriatric Association in Chicago.
June 30, 2003
Neurochem reported positive results from a phase II trial investigating Alzhemed, a disease-modifying agent for the treatment of Alzheimer’s disease (AD). Results showed that subjects in the 300 mg treatment group, who have continued in the open-label extension study, showed a stabilization on cognitive function tests (ADAS-Cog) after six months. Alzhemed subjects had a marked decrease of amyloid beta (A beta 42), greater than or equal to 50 pg/ml, in the CSF after three-months. A reduction as high as 70% was seen in the two highest dose groups. The most frequent treatment related adverse events reported were nausea and vomiting. The multi-center, randomized, double blind, placebo-controlled and parallel-designed study enrolled 58 subjects with mild-to-moderate AD. Subjects were randomized to receive either placebo or Alzhemed at daily doses of 100 mg, 200 mg or 300 mg for 12 weeks. Subjects who completed the three-month study could enroll in an open-label extension study for an additional nine months.
May 19, 2003
NicOx reported positive results from a phase I trial investigating HCT 1026, a flurbiprofen derivative for the treatment of Alzheimer’s disease. Results demonstrated penetration of the bloodbrain barrier and presence of effective drug concentrations in cerebrospinal fluid. Data showed that pharmacologically effective drug levels inhibiting prostaglandins were found in cerebrospinal fluid after repeated oral administration of HCT 1026 (75mg / 150mg) for seven days. In addition, endoscopic analysis has shown that the drug demonstrated superior gastric tolerability. The randomized, parallel group, multiple dose study enrolled 24 subjects and was designed primarily to assess drug penetration into the cerebrospinal fluid. Previous studies in more than 200 subjects have shown positive overall tolerability with HCT 1026.
Positive results were reported from a pilot study investigating Unimed Pharmaceutical’s Marinol (dronabinol), an approved synthetic THC compound for the new indication of Alzheimer’s disease. The study suggested dronabinol might reduce agitation and improve appetite. Results after one month found significantly reduced agitation was achieved in six subjects. No adverse events, such as falls, syncope, seizures or exacerbation of agitation or depression were reported. Subjects received 5 to 10mg per day of dronabinol in two doses in addition to being treated with atypical neuroleptics and at least four medications to control behavior. The study enrolled nine subjects who met the Diagnostic and Statistical Manual of Mental disorders criteria for possible Alzheimer's disease. Results were presented at the annual meeting of the American Geriatrics Society.
November 18, 2002
Neurogen reported negative results from a phase II trial investigating NGD 97-1, for the treatment of Alzheimer's disease. In preclinical animal models, the drug selectively reduced the activity of the neurotransmitter gamma-aminobutyric acid (GABA) in the memory centers of the brain, improving cognitive function. However, the study conducted by Neurogen's partner, Pfizer, did not show a therapeutic effect among the 200 subjects treated. Neurogen does not expect Pfizer to advance NGD 97-1 further. In addition to these results, Neurogen reported positive data from a phase I trial investigating NGD 2000-1, a C5a receptor antagonist for the treatment of inflammatory disorders. The study, a double blind, placebo-controlled trial in normal healthy volunteers demonstrated the drug was safe and well tolerated.
September 16, 2002
In a recently completed six month phase III study, 403 subjects with moderate-to-severe Alzheimer's disease showed significant improvements in cognition when Memantine was added to their standard donepezil (Aricept) therapeutic regimen. Subjects evaluated in this double-blind, parallel arm, placebo-controlled study were treated with either Memantine 20 mg per day or placebo in addition to their donepezil therapy for six months. Subjects were treated with a stable dose of donepezil for at least six months prior to randomization. At the end of the treatment period, daily 20 mg of Memantine plus donepezil was statistically superior to placebo plus donepezil treatment on both the ADCS-ADL (function) and the SID (Cognition) measures. Also, Memantine group, on the CIBIC-PLUS scores (global measure), demonstrated a more statistically significant benefit than the placebo group. This study of Memantine was sponsored by Forest Laboratories and its partner Neurobiological Technologies.
May 6, 2002
Preliminary results indicate that a placebo-controlled study of Neotrofin in subjects with Alzheimer's disease did not produce statistically significant results at 12 weeks capable of supporting FDA approval. However, the data did show that some Alzheimer's subjects receiving Neotrofin experienced improvement in ADAS-cog scores and clinical global change ratings, which were the primary endpoints of the trial. NeoTherapeutics is awaiting results from phase II trials of Neotrofin in Parkinson's disease, spinal cord injury and chemotherapy-induced neuropathy.
January 24, 2002
Wyeth-Ayerst and Elan have decided to temporarily suspend dosing in a phase IIa trial of AN-1792 (AIP-001), an immunotherapeutic for mild-to-moderate Alzheimer's disease. The decision came after four subjects in France were reported to have clinical signs consistent with inflammation in the central nervous system. The cause of the inflammation is unknown at this time. The companies will provide further guidance regarding the resumption of dosing after consulting with an independent safety monitoring committee, study physicians and regulatory authorities.