Neurologic Disorders

July 3, 2017

bluebird bio announced topline interim data from the initial cohort of 17 patients in the ongoing phase II/III Starbeam Study (ALD-102) evaluating Lenti-D investigational gene therapy in boys under 18 years old with cerebral adrenoleukodystrophy (CALD). The Starbeam Study involves transplantation with a patient’s own stem cells, which are modified to contain functional copies of the ABCD1 gene. This gene addition should result in the production of functional adrenoleukodystrophy protein (ALDP), a protein critical for the breakdown of very long chain fatty acids (VLCFAs). Buildup of VLCFAs in the central nervous system contributes to neurodegeneration in CALD. As of June 13, 2017, 17 patients with CALD have completed two years of follow-up post-Lenti-D treatment, with 15/17 (88%) remaining free of major functional disabilities (MFDs), the primary endpoint of the trial. This exceeds the pre-defined interim efficacy benchmark for the study of MFD-free survival of 76%, derived from the literature and based on clinical data from an earlier observational study describing that natural history of CALD and outcomes from allogeneic HSCT. The study was recently expanded and is currently enrolling additional patients in Europe and the U.S.

April 15, 2013

Biogen Idec released results from a phase IIb trial of DAC HYP (daclizumab high-yield process) for multiple sclerosis (MS). This randomized, double-blind, placebo-controlled, one-year, dose-ranging study, SELECT, enrolled 621 patients with relapsing-remitting MS (RRMS) per McDonald criteria 1-4 and a baseline EDSS score between 0.0 and 5.5. Subjects received DAC HYP 150mg or 300mg once every four weeks, or placebo. Results demonstrate that both 150mg and 300mg doses of DAC HYP significantly reduced the annualized relapse rate (ARR) by 54% (p<0.0001) and 50% (p=0.0002), respectively, compared to placebo. In addition, results demonstrated DAC HYP reduced MS brain lesions compared to placebo. Both doses of DAC HYP also demonstrated a trend in improvements in quality of life (QoL) compared to placebo, as measured by the Multiple Sclerosis Impact Scale (MSIS-29) physical impact score. The drug was well tolerated. The most frequent adverse events were similar in all three study groups. Biogen Idec did not note its plans for DAC HYP.

April 1, 2013

Biotie issued results from a phase IIb trial of tozadenant (SYN115) in Parkinson’s disease (PD). This double-blind, international, 12-week study enrolled 337 patients with Parkinson’s disease experiencing levodopa-related end-of-dose wearing off. Subjects received tozadenant 60mg, 120mg, 180mg or 240mg twice daily, or matching placebo. Significant reductions in mean placebo-corrected change from baseline in “off” time were observed with tozadenant 120mg BID (-1.1 hr, p=0.0039) and 180mg BID (-1.2 hr, p=0.0039). The amount of time patients spent in the “on” time with troublesome dyskinesia was not significantly increased in any tozadenant group. Mean placebo-corrected scores on the UPDRS part III significantly improved with tozadenant 120mg BID (-2.2, p=0.0325) and 180mg BID (-2.5, p=0.0325), and mean placebo-corrected UPDRS I-III scores improved significantly in all tozadenant groups (all groups, p<0.03). The most frequent adverse events in the combined tozadenant groups were dyskinesia, nausea, dizziness, constipation, PD worsening, insomnia and falls. Biotie is working closely with UCB Pharma for further development of tozadenant and plan to start the phase III program by 2015.

March 25, 2013

Biogen Idec reported results from a phase III trial of Plegridy (peginterferon beta-1a) for the treatment of relapsing-remitting multiple sclerosis (RRMS). This multi-center, randomized, double-blind, parallel-group, placebo-controlled study, ADVANCE, enrolled 1,516 patients with RRMS. Subjects received 125mcg Plegridy subcutaneously every two weeks or every four weeks, or placebo. Results showed both Plegridy arms met the primary endpoint of reducing annualized relapse rate (ARR), with the two-week arm achieving 36% at one year compared to placebo (p=0.0007). The two-week cycle of Plegridy also reduced the proportion of patients who relapsed by 39% compared to placebo (p=0.0003). Futhermore, the two-week arm of Plegridy demonstrated significant positive effects on disability progression by reducing the risk of 12-week confirmed disability progression, as measured by the Expanded Disability Status Scale (EDSS), by 38% compared to placebo (p=0.0383). The drug was well tolerated. The most frequent adverse events were infections, redness at the injection site and influenza-like illness. Based on these data, Biogen Idec has initiated an open-label extension study called ATTAIN.

December 10, 2012

Upsher-Smith Laboratories reported results from a phase I trial of USL261 for the treatment of seizures in epilepsy. This randomized, open-label study enrolled 90 patients with epilepsy between the ages of 12 and 62 on stable antiepileptic drug (AED) regimens. Subjects received a single dose of 2.5mg, 5mg or 7.5mg USL261 by a unit-dose nasal spray device. Results demonstrated that maximum midazolam plasma concentrations were rapidly achieved after dosing with USL261. Furthermore, onset of pharmacodynamic effects were seen as early as 10 minutes, and scores of each instrument returned to near baseline levels by four hours after the administration of USL261. Investigators concluded that midazolam Cmax was rapidly achieved after dosing with USL261, and both midazolam and 1-OHMZ were rapidly eliminated, with mean t(1/2) between three and four hours. The drug was well tolerated. Upsher-Smith also is studying USL261 in an ongoing global phase III trial called ARTEMIS1.

December 3, 2012

Cytokinetics issued results from a phase IIa trial of tirasemtiv for the treatment of generalized myasthenia gravis (MG). This double-blind, randomized, three-period crossover, placebo-controlled study, CY 4023, enrolled 32 patients with generalized MG. Subjects received separate, single doses of tirasemtiv 250mg, tirasemtiv 500mg and placebo in random order approximately one week apart. Since the study was a hypothesis-generating trial, no single primary efficacy endpoint was pre-specified. Results showed that six hours after dosing, improvements (decreases) in the Quantitative MG score (QMG) were related to the tirasemtiv dose in a statistical significant manner (-0.49 QMG points per 250mg; p=0.02). Decreases in certain components of the QMG and their relationships to dose were statistically significant or borderline significant. Also at six hours after dosing, increases in the percent predicted forced vital capacity were statistically significantly related to the dose level of tirasemtiv (2.2% per 250mg; p=0.04), as were the individual comparisons of each dose level of tirasemtiv versus placebo. The drug was well tolerated. The most frequent adverse event was dizziness. Cytokinetics has initiated a phase IIb trial of tirasemtiv in patients with ALS. Tirasemtiv has also been granted Orphan Drug designation and Fast Track status by the FDA.

Supernus Pharmaceuticals reported results from a phase IIb trial of SPN-810 for the treatment of impulsive aggression in attention deficit and hyperactivity disorder (ADHD). This multi-center, randomized, double-blind, placebo-controlled study enrolled 121 patients ages six to 12 diagnosed with ADHD and characterized by impulsive aggression that was not controlled by optimal stimulant and psychosocial treatment. Subjects received low, medium or high doses of SPN-810, or placebo. Results showed that for all patients, low and medium doses of SPN-810 met the efficacy endpoint of rate of remission of aggression and showed statistical significance versus placebo with p-values of 0.009 and 0.043 and percent of patients with R-MOAS remission of 51.9% and 40.0%, respectively. The low and medium doses showed a reduction in score for the R-MOAS of 62.6% and 57.9%, respectively, with p-values of 0.071 and 0.115. For patients of 30kg or more in weight, the low and medium doses of SPN-810 showed statistical significance versus placebo on the change in R-MOAS primary endpoint with p-values of 0.024 and 0.049, and high percent reduction in the R-MOAS scores of 80.9% and 75.2%, respectively. The drug well tolerated. Based on these data, Supernus Pharmaceuticals will meet with the FDA to discuss the design and protocol for a phase III trial of SPN-810 in impulsive aggression in ADHD.

November 19, 2012

Depomed reported results from a phase II trial of DM-1992 for advanced Parkinson’s disease. This 10-day, randomized, active-controlled, open-label, crossover study enrolled 34 patients with advanced Parkinson’s with motor fluctuations. Subjects received either DM-1992 twice daily or a generic version of immediate-release carbidopa/levodopa (IR CD/LD) dosed as needed (mean daily dosing frequency = 4.8) for six days, followed by a three-day patient self-assessment period and one in-clinical day. Patients’ mean baseline “off” time during waking hours was 5.4 hours per day (32.5%), compared to 4.5 hours (27.2%) during the DM-1992 self-assessment period and 5.5 hours (33.5%) for the IR CD/LD comparator. The reduction in percent “off” time reported during the DM-1992 patient self-assessment period relative to the IR CD/LD comparator was statistically significant (p=0.047). DM-1992 was generally well tolerated. There were no serious adverse events.

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.

Teva Pharmaceutical reported results from a phase III trial of Copaxone (glatiramer acetate) for multiple sclerosis. This multinational, randomized, double-blind, placebo-controlled study, GALA, enrolled 1,400 patients with relapsing-remitting MS (RRMS). Subjects received Copaxone 40mg/1ml (double the drug’s current marketed dose) or placebo via subcutaneous injection three times a week for 12 months. Data demonstrated Copaxone 40mg/1ml significantly reduced annualized relapse rates (ARR) by 34.4% (p<0.0001) versus placebo. A significant 34.4% reduction in the cumulative number of new and enlarging T2 lesions (p<0.0001) and a significant 44.8% reduction in the cumulative number of gadolinium-enhancing (GdE) legions (p<0.0001) was observed in patients treated with Copaxone 40mg/1ml versus placebo. At 12 months, there was no significant difference in percent change of brain volume between Copaxone and placebo. The drug was well tolerated. The most frequent adverse events were injection site reactions, headaches and nasopharyngitis.

May 7, 2012

Ultragenyx Pharmaceutical reported results from a phase I study of UX001 (extended release sialic acid) for the treatment of hereditary inclusion body myopathy (HIBM). This first-in-human, multi-center, sequential dose-escalation study enrolled 26 patients. Subjects received SA-ER tablets orally at one of five dose levels in the single-dose phase and one of four dose levels in the repeat-dose phase. Pharmacokinetic analysis based on the study showed single doses of UX001 are absorbed and provide significant drug levels over a 12-16 hour period. On repeated three-times-per-day dosing, serum-free sialic acid concentrations reached relatively steady levels over a 24-hour cycle. Preliminary data showed UX001 was well-tolerated at the doses evaluated, with no serious adverse events reported. Based on these data, Ultragenyx plans to initiate an international phase II study of UX001 in the second quarter of 2012.

August 2, 2010

Seaside Therapeutics released positive results from a phase II trial of STX209 for the treatment of Fragile X syndrome. This randomized, double-blind, placebo-controlled, two-period crossover study enrolled 63 subjects, ranging in age from six to 40 years old. Dosing was conducted as a flexible titration, every three days, to the optimal titrated dose (OTD). The starting dose was 1 mg twice a day and was gradually increased up to 10 mg twice a day for subjects <11 years and up to 10 mg three times a day for subjects ≥12 years. OTD was continued for the remainder of the four-week treatment period. Data are from 54 evaluable subjects. While improvement was noted for the primary endpoint, the Irritability subscale of the Aberrant Behavior Checklist, statistical significance was not reached versus placebo. STX209 consistently showed a positive trend for all global measures, including investigators assessments of Clinical Global Impressions of Improvement (p≡0.18) and Severity (p<0.10) and investigator (p<0.10) and caregiver treatment preference (p<0.10). STX209 was well tolerated and there were no metabolic side effects.

May 19, 2008

Alseres released positive interim results from a phase I/IIa trial of Cethrin for the treatment of neurological recovery following acute spinal cord injury. This open label study enrolled 48 subjects in the US and Canada with thoracic or cervical spinal cord injury. The subjects received escalating doses of Cethrin (0.3, 1, 3, 6 or 9 mg) administered to the injured spinal cord during spinal decompression surgery. Neurological outcomes were measured using the American Spinal Injury Association (ASIA) Impairment Scale at 0, 1.5, 3, 6 and 12 months after treatment. Data is from 37 subjects, all with cervical injuries, who received doses up to 6 mg and who had reached the final 12 month follow up evaluation. Data from six and twelve months showed 38% of the subjects demonstrated a 2-grade or better ASIA grade improvement. Subgroup analysis indicated a dose related response with 43% of the subjects from the 1 and 3 mg dose groups demonstrating improvement of at least 2 ASIA grades. Two of these three subjects improved 3 levels from ASIA grade A to ASIA grade D. Subgroup analysis of twelve month mean motor score changes showed improvement in both the 1 and 3 mg dosage groups with mean motor score changes of 16.3 points in the 1 mg and 27.3 points in the 3 mg doses. Hence, the most effective Cethrin doses for this population were determined to be 1 and 3 milligrams. Dosing in the 9 mg cervical and thoracic cohorts is currently underway. Based on positive data Alseres plans to commence a phase IIb trial in the second half of 2008.

December 10, 2007

Avicena released positive results from a phase II trial of AL-08 for the treatment of Amyotrophic Lateral Sclerosis (ALS). This randomized, double-blind, selection trial enrolled one hundred and twenty subjects who received AL-08 in combination with minocycline or AL-08 in combination with celecoxib. The primary objective was to determine treatment selection based on which drug combination appeared to slow deterioration in the ALS-Functional Score. Results showed subjects treated with AL-08/celcoxib showed a smaller mean functional decline versus AL-08/minocycline. At the end of the trial, the decline in ALS-Functional Score in both treatment arms was compared separately to the mean historical control group at a 0.05 significance level. The mean decline in ALS-Functional Score was 5.27 in the celecoxib/creatine arm, compared to 6.47 in the minocycline/creatine arm, and 5.82 in the historical control group. Based on the results, Avicena plans to move forward with phase III trials.

Teva released positive interim results from a phase III trial of Copaxone for the treatment of multiple sclerosis (MS). This multi-national, multi-center, prospective, double-blind, randomized study, dubbed PreCISe, enrolled 481 subjects presenting with a single clinical episode and MRI suggestive of MS. The subjects received either Copaxone 20mg/day or placebo as a subcutaneous injection. Treatment was continued for up to 36 months, unless a second attack was experienced and they were diagnosed with clinically definite MS (CDMS).The primary outcome was time to CDMS, based on a second clinical attack. Copaxone reduced the risk of developing CDMS by 44% versus placebo, and prolonged the quartile time to disease conversion to 722 days versus 336 days in those subjects receiving placebo (hazard ratio 0.56, p=0.0005). At this interim analysis, the proportion of subjects who had developed CDMS was reduced from 43% in the placebo group to only 25% in the Copaxone group (p less than 0.0001). Based on the results, Teva plans to file for regulatory approval in Europe, the U.S. and Canada for the treatment of subjects with a first clinical event suggestive of MS.

UCB Pharma reported positive results from two phase II trials of lacosamide for the treatment of epilepsy. This double-blind, randomized, parallel-group, placebo-controlled study enrolled four-hundred and five subjects with refractory partial onset seizures, which were uncontrolled despite treatment with one to three anti-epileptic drugs. The subjects received lacosamide 400 mg/day or 600 mg/day (given in two doses), or placebo for twelve weeks. The median reduction in seizure frequency from baseline was significantly greater for lacosamide than placebo: 37.3%, 37.8% and 20.8% for lacosamide 400 mg/day, 600 mg/day, and placebo, respectively. Significantly more subjects achieved a 50% or greater reduction in seizure frequency with lacosamide than placebo: 38.3%, 41.2% and 18.3% for lacosamide 400 mg/day, 600 mg/day, and placebo, respectively. Nine subjects who completed the Maintenance Phase were seizure free throughout the entire twelve-weeks: four in the 400 mg/day group (2.5%) and five in the 600 mg/day group (8.1%). The subjects who completed the SP754 trial had the option to transition to an open-label extension study, which was designed to evaluate long-term the efficacy and safety profile of lacosamide. A total of three hundred and seventy subjects were enrolled and received a median lacosamide dose of 400 mg/day. Of the 370 subjects, 284 (76.8%) were exposed to lacosamide for more than twelve months, 224 (60.5%) for more than twenty-four months, and 140 (37.8%) for more than thirty six months. After 5.5 years the median percent reduction in seizure frequency across all prior treatment groups was 45.9%. Additionally, 46.6% of subjects had at least a 50% reduction in seizure frequency with lacosamide. The long-term use of lacosamide was determined to be safe and well tolerated. An NDA is currently under review by the FDA.

October 22, 2007

Anesiva issued positive results from a phase III trial of Zingo for the treatment of pain associated with venous access procedures in adults. This randomized, double-blind study enrolled 699 adult subjects in the US. The subjects were treated with Zingo or placebo one to three minutes prior to undergoing intravenous cannulation or venipuncture. The primary endpoint was pain upon needle insertion utilizing the Visual Analog Scale (VAS) for pain. The mean pain score in the Zingo-treated group was significantly lower than in the placebo group (p = 0.003). Based on the results, Anesiva plans to file a sNDA with the FDA in early 2008.

Genzyme issued positive three-year results from a phase II trial of alemtuzumab for the treatment of multiple sclerosis (MS). This study enrolled 334 subjects with active relapsing-remitting MS in the US and Europe. The subjects were randomized to receive alemtuzumab at one of two doses (12 or 24/mg per day intravenously for five days at initial treatment, and three days of re-treatment after 12 months with an option to treat again at 24 months), or Rebif (44 mcg administered by subcutaneous injection three times per week). The co-primary endpoints, the rate of relapse of MS symptoms and the time to Sustained Accumulation of Disability over six months as measured by Expanded Disability Status Scale [EDSS], were both reached with statistical significance. The subjects treated with alemtuzumab experienced at least a 73% reduction in the risk for relapse after three years of follow up when compared to those treated with Rebif (p=0.00396). In addition, the subjects in the alemtuzumab arm experienced at least a 70% reduction in the risk for progression of clinically significant disability when compared to those treated with Rebif (p=0.01646). Full results from this trial are expected to be released in the spring of 2008.

PDL Biopharma and Biogen released positive results from an ongoing phase II trial of daclizumab for the treatment of multiple sclerosis. This randomized, double-blind, placebo-controlled trial enrolled 230 subjects in the US and Europe. Subjects received daclizumab at 2 mg/kg every two weeks, daclizumab at 1 mg/kg every four weeks or placebo, all in combination with ongoing interferon beta treatment, for a treatment duration of 24 weeks. The primary endpoint, a significant reduction of the number of new or enlarged gadolinium-contrast-enhancing lesions (Gd-CELs) at week 24 compared to placebo, was achieved. The subjects in the 2 mg/kg group experienced 72% fewer new or enlarged Gd+ on average compared to the placebo group (p=0.004). While not statistically significant, the subjects in the 1 mg/kg group experienced a 25% reduction in new lesions compared to placebo. The secondary endpoint, relapse rate, indicated that daclizumab reduced the annual relapse rate over placebo. However, the results did not reach statistical significance. Based on the results PDL and Biogen plan to move ahead with the development of daclizumab.

September 17, 2007

Santhera reported positive results from a clinical trial of SNT-MC17 for the treatment of Friedreich's Ataxia (FRDA). This 6-month, randomized, double-blind, placebo-controlled study was conducted by the US National Institutes of Health. The trial enrolled 48 subjects, aged 9 to 17 years, with genetically confirmed FRDA. The subjects received placebo or one of three doses of SNT-MC17. The primary endpoint was the change from baseline in urinary 8-hydroxy-2'-deoxyguanosine (8OH2'dG). Secondary endpoints included the change on the International Cooperative Ataxia Rating Scale (ICARS) and the Friedreich Ataxia Rating Scale (FARS). The endpoints were achieved, with dose dependent improvements observed in each. In addition, there was a change in neurological function from baseline of 10 to 17%. Phase III trials of SNT-MC17 are currently underway.

August 6, 2007

Intellect Neurosciences reported positive results from a phase I trial of OXIGON for the treatment of neurological disorders. This double-blind, randomized, placebo-controlled, single-escalating dose study enrolled 54 healthy elderly subjects. The trial was designed to determine the safety, tolerability and pharmacokinetics of OXIGON with and without food interactions. Treatment was shown to be safe and well tolerated, with no serious adverse events reported up to the highest single dose of 1.2 grams. Data from a phase Ib trial were expected shortly.

Phytopharm announced positive results from a phase Ib trial of Myogane for the treatment of Amyotrophic Lateral Sclerosis (ALS). This randomized, double blind, placebo-controlled, trial enrolled healthy subjects in the UK. Subjects received single escalating oral doses of Myogane. The study demonstrated good safety, tolerability and pharmacokinetic profiles, as well as an excellent absorption profile. The highest dose administered (640 mg) was well tolerated with no adverse events. Based on the results, Phytopharm plans to advance Myogane into phase II trials.

Targacept issued positive results from a phase II trial of mecamylamine HCL as add-on therapy for the treatment of depression. This trial, dubbed STAR*D (Sequenced Treatment Alternatives to Relieve Depression), enrolled 192 subjects in the US and India. All subjects were inadequate responders to first-line citalopram therapy. After a 3 to 5 day washout period, subjects were started on citalopram in an open label phase. . Citalopram therapy started at 20 mg once daily and was increased at week 2 to 40 mg once daily. This monotherapy lasted 6 weeks. After evaluation, those subjects considered inadequate responders were randomized in a double-blind fashion to receive either placebo or mecamylamine as an add-on to continued citalopram therapy, a combination known as TRIDMAC. Mecamylamine was started at 5 mg daily and could be increased to 7.5 mg after 2 weeks of treatment. After a further 2 weeks, medication could be increased to 10 mg. Results showed mecamylamine was superior to placebo, when added to subjects who were inadequate responders to first-line treatment with citalopram. Mecamylamine was also superior to placebo in treating symptoms of irritability. The treatment combination was generally well tolerated.

January 29, 2007

Pharmos reported negative results from a phase IIa trial of cannabinor for the treatment of capsaicin-induced pain. This randomized, double-blinded, two-way crossover trial enrolled 24 healthy male subjects who received 48mg of cannabinor administered intravenously or placebo. The trial was designed to determine the effect of cannabinor versus placebo on capsaicin-evoked allodynia (pain resulting from a non- noxious stimulus to the skin) and hyperalgesia (abnormally increased pain sense). Treatment was safe and well tolerated. However, the primary endpoint of positive analgesic effects compared to placebo, was not reached. Based on the results, Pharmos plans to move the development of cannabinor towards the treatment of other types of pain including neuropathic pain and nociceptive pain.

October 3, 2005

Neurologix issued positive interim results of a phase I trial of their AAV-GAD viral-vector gene therapy, for the treatment of Parkinson's disease (PD), at the 19th Annual Symposia on the Etiology, Pathogenesis and Treatment of Parkinson's Disease and Other Movement Disorders in San Diego. Primary safety data yielded a positive overall tolerability profile. Preliminary efficacy data were also positive, with a statistically significant 27% improvement in symptom severity score on the side of the body corresponding to the treated part of the brain, as measured on the Unified Parkinson Disease Rating Scale, relative to baseline (p=0.04); the untreated side experienced no significant improvement. Significant decreases in the extent of abnormal metabolism associated with the disease were also noted in drug-treated portions of the brain vs. baseline; the corresponding structure in the untreated side of the brain experienced progressive increases in abnormal function. This open-label dose- escalation study enrolled 12 PD patients, who received one of 3 single doses of the gene therapy (3.5, 10 or 35 billion viral particles) via unilateral intracerebral catheter infusion into the subthalamic nucleus, followed by observational follow-up at 1, 3, 6 and 12 months.

July 11, 2005

Vasogen issued positive results of a phase I trial of VP025, for the treatment of inflammatory central nervous system responses associated with neurological diseases such as Alzheimer's disease. Trial data met primary safety endpoints, with low, medium, and high doses of the drug producing no serious adverse events and a positive tolerability profile compare to placebo. This double-blind, placebo-controlled, dose-escalation study enrolled 24 healthy subjects, who received three doses of the drug and placebo. Based on these results, Vasogen announced plans to initiate phase II trials of the drug in patients with neuro-inflammatory disorders in the near future.

April 4, 2005

Aeolus Pharmaceuticals reported interim results from a phase I trial investigating AEOL 10150, a antioxidant neuroprotectant under development for the treatment of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease). Interim data demonstrated that was well tolerated compared to placebo. Results showed that plasma AUC values ranged from 354.2 ng*hr/mL in the 3 mg group to 4579.9 ng*hr/mL in the 30 mg group. Cmax ranged from 114.8 ng/mL to 733.4 ng/mL, and mean Tmax ranged from 0.5 to 1.3 hours in these same groups. The half-life of AEOL 10150 ranged from 2.61 to 5.25 hours. The most frequently reported adverse events were injection site reactions, dizziness and headache. No serious adverse events were reported. The multi-center, double-blind, randomized, placebo-controlled escalating single dose study is enrolling up to 5 subjects with ALS. The study is designed to evaluate the safety, tolerability and pharmacokinetics of the drug administered by subcutaneous injection. Single doses of up to six levels of AEOL 10150(3, 12, 30, 45, 60, and 75 mg) are being administered.

Guilford Pharmaceuticals issued results of a phase III trial of their investigational sedative Aquavan (GPI-15715). Primary efficacy data met their endpoints, with 96% of subjects receiving Aquavan achieving satisfactory sedation, as measured in the study by patient performance on the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) diagnostic scale, and by the absence of need for additional sedative medication or ventilation assistance. Sedation response generally occurred within 2 minutes, with recovery from the procedure within 11 minutes. The sedation produced by Aquavan was generally observed to be deeper and longer than with midazolam, which may have contributed to the significantly higher incidence of adverse events with the drug, compared to midazolam. This randomized, open-label study enrolled 278 patients, who received treatment with Aquavan (n=209) or placebo (n=69) during elective colonoscopy. Guilford announced that, due to the high incidence of adverse events, it was suspending enrollment in all of its ongoing trials of Aquavan, pending investigation of lower-dose treatment regimens.

January 19, 2004

XenoPort reported positive results from a phase I trial investigating XP13512, a transported prodrug of gabapentin. Results demonstrated that XP13512 was rapidly absorbed and was converted to gabapentin. Reported adverse effects were mild and consistent with those previously reported for the drug Neurontin. At the highest dose tested, mean gabapentin exposure after treatment was approximately 2.5 times higher than that of Neurontin. In addition, data showed that XP13512 provided substantially higher gabapentin exposure than equimolar Neurontin in all subjects. The randomized, placebo-controlled, double-blind study was designed to test the safety, tolerability and pharmacokinetics of XP13512 in healthy adults. Subjects were given five ascending single doses of an immediate-release formulation.

October 13, 2003

Indevus Pharmaceuticals reported positive results from a phase II trial investigating IP 751 (CT-3), an analgesic cannabinoid for the treatment of neuropathic pain. Results showed that IP 751 significantly reduced the degree of neuropathic pain without causing psychoactive adverse events. Data demonstrated that the degree of pain experienced by subjects decreased significantly during periods of treatment with IP 751. In addition, no significant differences were observed between treatments of measurements of cognitive function and prototypic subjective experiences. The two-week, randomized, crossover study enrolled 21 subjects with chronic neuropathic pain from spinal nerve injuries. Subjects received IP 751, (20 mg-40mg given 2x a day) or placebo. The study was conducted at the Hannover Medical School in Germany. Results were reported in the Journal of the American Medical Association.

December 9, 2002

Transkaryotic Therapies reported negative preliminary results from a phase III trial investigating Replagal (agalsidase alfa), an enzyme replacement for the treatment of Fabry Disease. Results showed that the preliminary data did not reach its primary end-point of renal function, as measured by glomerular filtration rate. The double blind, placebo-controlled study enrolled 80 subjects with Fabry Disease. Subjects were given Replagal (.2 mg/kg) every other week over a 40-minute intravenous infusion in a six-month regimen.

January 24, 2002

Phase II trial results suggest that Amarin's LAX-101 produces improvement in subjects with advanced Huntington's disease (HD). In the six-month randomized, double-blind and placebo-controlled trial, three HD subjects received LAX-101 and four received placebo. After six months of treatment, all three subjects receiving LAX-101 showed significant improvement on the orofacial component of the Unified Huntington's Disease Rating Scale (UHDRS). A mean 34% improvement was observed for subjects receiving LAX-101, compared to a mean 23% decline for placebo-treated subjects. Improvement was also observed in the total movement score of the UHDRS, with a mean 16% improvement for the LAX-101 group, compared to a mean 38% decline for the subjects receiving placebo.

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