October 3, 2016
Adamas Pharmaceuticals released results of the EASE LID 3 study, the second phase III trial of ADS-5102 (amantadine hydrochloride) extended-release capsules for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease (PD). The trial met its primary endpoint, the reduction of the UDysRS (Unified Dyskinesia Rating Scale) total score at week 12 (p<0.0001), reflecting a decrease in the duration, intensity and disability associated with LID. Results showed a statistically significant reduction (p=0.0009) in LID at 12 weeks for patients who received ADS-5102 versus placebo as assessed by the UDysRS. This represents a 23% reduction in LID for ADS-5102-treated patients compared to placebo. The reduction in LID was maintained at 24 weeks (p=0.0008), a key secondary analysis. In this study, there were four additional key secondary analyses based on patient diary data. All achieved statistical significance. A statistically significant reduction in OFF time (a key secondary endpoint) was observed, as measured by patient reported home diaries. Notably, at week 12, ADS-5102 significantly increased ON time without troublesome dyskinesia by 2.7 hours versus placebo and reduced OFF time by 0.9 hours. These effects were maintained at week 24. The company will submit a New Drug Application for ADS-5102 to the FDA later this year.
December 22, 2014
Cynapsus Therapeutics issued results
from a phase II study of APL-130277 for
the management of OFF motor symptoms
of Parkinson’s disease. In the multicenter,
open-label study, APL-130277 was assessed
in 16 patients with Parkinson’s disease
who experience OFF episodes, with a total
duration of OFF of at least two hours daily.
Patients were then given escalating doses of
APL-130277 (at a minimum of three hours
between doses) until ON was achieved. All
five doses of APL-130277 used in the study
(10mg, 15mg, 20mg, 25mg and 30mg)
resulted in patients moving from OFF to
ON. The onset of a clinically meaningful
improvement was seen in as early as 10 minutes
and lasted up to 90 minutes, the last
time point measured in this study. The mean
time to ON as reported by study staff was
22 minutes. Preliminary data show several
subjects converted to ON with the 10mg low
dose, and 14 of 16 subjects converted ON
with all available doses. The maximum mean
change from baseline Unified Parkinson’s
Disease Rating Scale (UPDRS) III was 18.4,
which is a large clinically important difference.
APL-130277 treatment was safe and
well-tolerated, with no local irritation, no
postural hypotension and a low number
of nausea events. Cynapsus is planning to
conduct pivotal studies of longer duration
and with larger patient numbers to confirm
these results. These pivotal studies are
expected to form the registration package
necessary for a 505(b)(2) New Drug Application
with the FDA expected to be submitted
August 11, 2014
AFFiRiS issued results of a phase I study ofAFF008, a vaccine against Parkinson’s disease. PD01A was applied at two different doses (15μg and 75μg) to 12 patients per group. All received four vaccinations in monthly intervals, and all completed the study. Eight patients on best medical care, including standard symptomatic medication, served as a control group. Each patient was regularly seen and evaluated during a 12-month period. Fifty percent of the vaccinated patients generated alpha-synuclein-specific antibodies as measured in serum samples. Additionally, vaccine-induced antibodies were detectable in cerebrospinal fluid. This induction of antibodies
against alpha-synuclein is preliminary evidence in support of the principle of AFFiRiS’ proprietary therapeutic vaccine. The Michael J. Fox Foundation will support a follow-up study testing a boost vaccination, the next step toward a phase II trial. The next study will take place in Austria and focus on assessing the immunological and clinical effects of a boost vaccination. Recruitment is expected to begin September.
July 22, 2013
Newron Pharmaceuticals reported results from a phase III trial of safinamide for the treatment of Parkinson’s disease. A six-month (24-week), randomized, double-blind, placebo-controlled international phase III trial enrolled 549 patients with mid- to late-stage idiopathic Parkinson’s (more than three years of disease duration) treated with optimized, stable doses of levodopa and standard of care (dopamine agonist, COMT inhibitor, anticholinergic and/or amantadine) for at least four weeks. Improvements of more than one hour in the patient and caregiver-rated ON and OFF time plus 30% or greater improvement in motor symptoms were seen in a significantly (p=0.018) larger proportion of patients than standard of care. Patients who were experiencing a minimum of one and a half hours of “OFF” time during the day were randomized equally to treatment with once-a-day safinamide (50mg to 100mg) or placebo (standard of care including levodopa) as adjunctive treatment. 484 patients completed the trial. The most commonly reported adverse events were nausea, urinary tract infections, falls, back pain and dyskinesia. Safinamide shows a rapid onset of efficacy with improvements being observed in ON-time (p=0.0003) and OFF-time (p<0.0001) from week two onwards.
July 15, 2013
Adamas Pharmaceuticals issued results from a phase II/III trial of ADS-5102 for the treatment of levodopa-induced dyskinesia (LID). This randomized, double-blind, placebo- controlled trial enrolled 83 male and female Parkinson’s disease subjects aged 30 to 85 years at 31 sites in the U.S. Participants were randomized to receive 260mg, 340mg or 420mg doses of ADS-5102 or placebo once-nightly for eight weeks with a two-week safety follow-up. Both the 340mg and 420mg ADS-5102 dose levels significantly reduced LID as measured by the change in UDysRS Total Score over eight weeks v. placebo. At the 340mg dose of ADS-5102, a treatment difference of 11 points (reduction in LID) was observed (p=0.005). The 420mg dose of ADS-5102 also met statistical significance with a treatment difference of 10 points (p=0.013). The adverse events reported were consistent with Parkinson’s disease and the known amantadine safety profile.
July 1, 2013
Adamas Pharmaceuticals issued results from a phase II/III trial of ADS-5102 (amantadine HCl extended release) capsules for the treatment of Levodopa-Induced Dyskinesia (LID) in Parkinson’s disease. This randomized, double-blind, placebo-controlled clinical trial enrolled 83 subjects aged 30 to 85 years old. Study participants were randomized to receive 260mg, 340mg, or 420mg doses of ADS-5102 or placebo once-nightly for eight weeks with a two-week safety follow-up. The study met its primary endpoint; both the 340mg and 420mg ADS-5102 dose levels significantly reduced LID as measured by the change in UDysRS Total Score over eight weeks v. placebo. The 420mg dose of ADS-5102 also met statistical significance with a treatment difference of 10 points (p=0.013). While the lowest dose tested of 260mg ADS-5102 reduced UDysRS by 5.6 points, it did not achieve statistical significance at week eight (p=0.159). The most commonly reported adverse events were constipation, dizziness, dry mouth, hallucination, fall, confusional state, headache, nausea and asthenia, each reported in two or more subjects in the active treatment groups.
April 29, 2013
Civitas Therapeutics released results from a phase IIa trial of CVT-301 for the treatment of Parkinson’s disease. This multi-center, randomized, double-blind, placebo-controlled, single-dose, cross-over study enrolled patients with intermittent debilitating motor fluctuations (OFF episodes) due to Parkinson’s disease. Subjects received CVT-301 25mg or 50mg, or placebo. Data demonstrated that administering CVT-301 to subjects in the OFF state produced a rapid and durable improvement in motor function. CVT-301 provided immediate L-dopa absorption and consistent increases in plasma concentrations in marked contrast to the delayed and variable L-dopa levels. CVT-301 was well tolerated. Civitas plans to present the comprehensive data from the study at a future scientific meeting. This study was funded in part by a grant from the Michael J. Fox Foundation.
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 11, 2013
NeuroDerm released results from a phase I trial of ND0612, a levodopa/carbidopa liquid formula administered continuously subcutaneously through a patch pump, under development for Parkinson’s disease. This double-blind, dose-escalation trial enrolled approximately 36 young, healthy adults. ND0612 was subcutaneously continuously-delivered for 24 hours. The subjects were assessed for safety and tolerability as well as for levodopa and carbidopa steady state plasma levels. ND0612 was shown to be safe and tolerable in all of the tested doses. In addition, clinically meaningful levodopa concentrations were reached and steady state levodopa concentrations were maintained in a practical manner, both day and night.
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.
June 25, 2012
Abbott Laboratories released results from a phase II trial of levodopa-carbidopa intestinal gel (LCIG) for the treatment of advanced Parkinson’s disease. This open-label study enrolled 354 patients. The gel was administered to subjects directly into the small intestine via a procedurally-implanted tube connected to a portable pump that delivers continuous supply of LCIG during awake hours. The gel was found to be safe and well tolerated. At week 54, subjects’ mean daily “off” time (poor mobility, slowness, etc.) had decreased by an average of 4.5 hours, while their “on” time without troublesome dyskinesia had increased by 5.1 hours. The most common adverse events were device insertion, abdominal pain, procedural pain and nausea. Abbott has already commenced phase III trials of LCIG.
March 26, 2012
Addex Therapeutics issued results from a phase IIa trial of dipraglurant for the treatment of Parkinsons disease levodopa-induced dyskinesia (PD-LID). This double-blind, placebo-controlled study enrolled 76 subjects with moderate or severe PD-LID. The subjects followed a dose-titration regimen, receiving 50mg doses from day 1 to day 14 and then 100mg from day 14 until day 28. Dipraglurant met the primary objective of the study by exhibiting a good safety and tolerability profile. Dipraglurant also demonstrated statistically significant reduction in LID severity with both 50mg and 100mg doses. Efficacy was measured using the modified Abnormal Involuntary Movement Scale (mAIMS). Peak mAIMS was significantly reduced on Day 1 (50mg; p≡0.042) and on Day 14 (100mg; p≡0.038).
August 29, 2011
Impax Laboratories and GlaxoSmithKline reported top-line results from a phase III trial of IPX066, an extended release capsule formulation of carbidopa-levodopa (CD-LD) for the treatment of the motor symptoms of Parkinson's Disease. This double-blind cross -over study, ASCEND-PD, enrolled 110 subjects on a stable dose of CLE, a combination treatment of carbidopa-levodopa and entacapone. The subjects were converted to IPX066 over a six-week period, then randomized to one of the two treatments (IPX066 or CLE) for two weeks and then crossed over to the other treatment for an additional two weeks after a one-week washout with IPX066. A total of 84 subjects completed the study. The primary endpoint was the percentage of off time during waking hours as measured by patient diary. Subjects entered the study with a baseline off time of 36.1% (5.9 hours), and at the end of the randomized IPX066 treatment phase subjects had off time of 24.0% (3.8 hours) during waking hours compared to 32.5% (5.2 hours) for CLE (p<0.0001). This represents a 33.5% decrease in percent off time for IPX066 from baseline vs. a 10% decrease for CLE.
March 21, 2011
Impax reported results from a phase III trial of IPX066, an extended release formulation of carbidopa-levodopa (CD-LD) for the treatment of Parkinsons disease (PD). This randomized, double-blind, active-control, parallel-group trial, ADVANCE-PD, treated 393 subjects with advanced PD experiencing motor fluctuations on a stable regimen of immediate release (IR) CD-LD. The subjects were randomized to a 13-week comparison of IPX066 versus IR CD-LD. Prior to randomization, subjects on a stable IR CD-LD dose regimen entered a three-week dose-adjustment or dose optimization period for IR CD-LD, followed by a six-week dose-conversion period to IPX066. IPX066 was administered three times a day. The primary endpoint was a comparison of the percentage of off time during waking hours. Subjects converted to IPX066 experienced a reduction from baseline of more than two hours in total off time and this effect was maintained in the group then randomized to IPX066 during the blinded study portion. The subjects converted to IPX066 demonstrated a 37% improvement from baseline versus a 17% improvement from baseline for IR CD-LD (p<0.0001). Similar results were seen in on time without troublesome dyskinesia, with an increase of 1.9 hours for IPX066 compared to an increase of 0.8 hours for IR CD-LD measured from baseline(p<0.001).
December 13, 2010
Nueraltus issued positive results from a phase I/II trial of NP002 for the treatment of dyskinesias resulting from levodopa therapy for Parkinson's disease. This randomized, double-blind, parallel group, placebo controlled trial enrolled 65 subjects. NP002 was administered concurrently with levodopa in escalating doses from 1 mg to 6 mg, four times a day. Each dose was taken for two weeks, except the highest dose, which was taken for four weeks. Clinically relevant trends and, in two cases, statistical superiority of NP002 over placebo were observed in a variety of physician- and patient-rated efficacy outcome measures relating to dyskinesias. The combination was found to be generally safe and well-tolerated.
November 22, 2010
Impax released positive results from a phase III trial of IPX066 for the treatment of early Parkinson's disease. This randomized, double blind, placebo-controlled study, APEX-PD, enrolled 350 subjects with early mild Parkinsons in North America and Europe. The subjects were placed in one of four dose groups: low, mid or high dose IPX066 or placebo. The primary endpoint, the change from baseline in the sum of Unified Parkinsons Disease Rating Scale (UPDRS) Parts II and III, was reached. All three doses of IPX066 showed significant improvement compared to placebo (p<0.0001 for all treatments). The mean sum of Parts II and III UPDRS score on IPX066 treatment improved 13.2 units (36%) compared to an improvement of 0.6 units (2%) with placebo treatment. IPX066 also demonstrated mean improvements in Clinician Global Impression of change and Patient Global Impression of change compared to placebo.
June 28, 2010
Neurologix released positive results from a phase II trial of NLX-P101, a gene therapy for the treatment of Parkinson's disease (PD). This randomized, double-blind, placebo controlled study enrolled 44 subjects with moderate to advanced PD who were not well-controlled on available medical therapy. The subjects received either an infusion of NLX-P101 bilaterally into each subthalamic nucleus, or a placebo infusion of a sterile saline solution. The primary efficacy endpoint was the difference in off-medication motor scores between the treated and placebo groups on the Unified Parkinson's Disease Rating Scale Part 3 (Motor section). Evaluations were made at baseline as well as one, three and six months after surgery. The subjects who received NLX-P101 experienced statistically significant and clinically meaningful improvements in off-medication motor scores compared to the subjects who received placebo surgery. This benefit was seen at one month and continued throughout the six month blinded study period. The results also demonstrated a positive safety profile for NLX-P101, with no serious adverse events related to the gene therapy or surgical procedure reported.
April 19, 2010
Synosia Therapeutics released positive results from a phase IIa trial of SYN-115 for the treatment of Parkinson s disease. This randomized, double-blind, placebo-controlled, cross-over study enrolled 27 subjects with mild-to-moderate disease. The subjects were randomized to one week each of SYN-115 (60 mg or 20 mg twice daily), washout, and then matching placebo, or the reverse, either alone or in combination with levodopa. The data demonstrated that SYN-115 significantly improves measures of motor and non-motor function both alone and in combination with levodopa. Total Unified Parkinsons Disease Rating Scale (UPDRS) motor score was 20 percent lower with SYN-115 as compared to placebo when administered with levodopa (p≡0.09). Improvement in two UPDRS measures of bradykinesia (finger taps and rapidly alternating movements of the hands) achieved statistical significance. In the 60 mg cohort, tapping speed was improved by SYN-115 as compared to placebo, both before (5%; p≡0.03) and during a sub-therapeutic IV infusion of levodopa (6%; p≡0.02).
September 28, 2009
Impax reported positive results from a phase II trial of IPX066 for the treatment of Parkinsons disease. This randomized, active-controlled, multi-center, one week per period, crossover study enrolled 27 subjects with advanced Parkinsons disease. The trial compared IPX066 (extended release carbidopa-levodopa) to Sinemet (standard of care) in terms of improving motor symptoms. IPX066 reduced "off" time during waking hours by 2 hours compared to Sinemet (3.8 hours of off time for IPX066 vs. 5.8 hours for Sinemet; P<0.0001). Corresponding effects were observed in the increase of "on" time, with no or non-troublesome dyskinesias. In addition, IPX066 significantly improved duration of motor function compared to Sinemet, with an effect sustained over 6 hours, as measured by walking times (P≡0.0023) and number of finger taps (P≡0.0093). IPX066 was generally well tolerated.
December 8, 2008
Schering Plough released positive results from a phase II trial of preladenant for the treatment of Parkinsons disease. This international, randomized, placebo-controlled, double-blind, dose-finding trial enrolled 253 subjects with moderate to severe disease, all of whom were on stable regimen of standard treatments. The subjects received four different doses of preladenant (1, 2, 5 or 10 mg twice daily) or placebo, both in combination with previous therapy. The treatment phase lasted 12 weeks. The primary endpoint was the reduction of "off-time" compared to placebo. This endpoint was achieved with statistical significance in the Preladenant 5 and 10 mg treatment arms when compared to the control arm. In addition, preladenant significantly increased the "on-time" at the same doses of 5 and 10 mg, a secondary endpoint of the study. This improvement was not associated with a proportional overall increase in dyskinesias. Preladenant was safe and well tolerated.
October 20, 2008
Neurogen reported positive results from two phase II studies of aplindore for the treatment of neurological indications. The first study was a placebo-controlled, single-blind, multi-center study in 27 subjects with restless legs syndrome. Each subject spent an adaptation night in the sleep laboratory followed by a placebo-dosed (baseline) night and then individual nights of sequentially increasing doses of aplindore from 0.05 mg to 0.2 mg. If a subject demonstrated less than a 50% reduction in PLMI (periodic limb movement index) from baseline at the 0.2 mg dose, the dose was escalated to a maximum of 0.7 mg. Results showed a significant reduction in the mean PLMI over placebo (p less than 0.0001). In the evaluable population the mean PLMI scores were 33.97, 13.88, 9.12, 8.24 and 8.20 for the placebo, 0.05 mg, 0.1 mg, 0.2 mg and the highest dose groups, respectively. On the basis of these significant results the study was terminated early. The second study was a dose-ranging, randomized, double-blind, placebo-controlled, parallel design study in 39 subjects with Parkinsons disease. The subjects were assigned to one of five cohorts, with each cohort consisting of a different dose escalation schedule and maximum dose. Following two weeks of titration to five different maximum daily doses, clinically and statistically significant improvement was observed in the Motor Score (Part III) of the Unified Parkinson Disease Rating Scale (UPDRS) in the cohorts dosed at 2 mg BID, 3 mg BID and 5 mg BID of aplindore compared to placebo. The subjects titrated to higher aplindore doses (9 mg BID and 15 mg BID) over the same two-week period of time showed improvements that did not separate statistically from placebo, suggesting a possible plateauing of the observed effect. Based on the data, Neurogen plans to move forward with the development of aplindore for both indications.
September 1, 2008
Teva and H. Lundbeck reported positive results from a phase III trial of Azilect for the treatment of Parkinsons disease. This double-blind, placebo-controlled trial, dubbed ADAGIO (Attenuation of Disease progression with Azilect GIven Once-daily), enrolled1,176 subjects with early, untreated Parkinson's disease across several international sites. The subjects were randomized to early-start treatment (72 weeks Azilect 1 or 2 mg once daily) or delayed-start treatment (36 weeks placebo followed by 36 weeks Azilect 1 or 2 mg once daily). The primary endpoint was disease progression, measured using three hierarchical endpoints based on the Total Score of the Unified Parkinson Disease Rating Scale (UPDRS) during the last 36 weeks of the 72-week study. Data showed that the subjects who took Azilect 1mg tablets once-daily upon trial entry demonstrated a significant improvement compared to those who initiated the drug nine months later. The 1mg dose met all three primary endpoints including: superiority of slopes in weeks 12-36 (-0.05; p=0.013); change from baseline to week 72 (-1.7 units; p=0.025) and non-inferiority of slopes (0.15 margin) in weeks 48-72 (0.0). Azilect was well tolerated. Teva plans to submit these results to the regulatory authorities in the U.S. and Europe.
July 21, 2008
Titan and Schering reported negative preliminary results from a phase IIb trial of Spheramine for the treatment of Parkinsons disease. This multicenter, double-blind, randomized, sham surgery-controlled study, dubbed STEPS, enrolled 71 subjects with late stage disease. The subjects received either Spheramine injections into both hemispheres or a sham surgical procedure. The primary endpoint was to evaluate the change in motor function from baseline to one year on study, using the Unified PD Rating Scale (UPDRS). Initial results showed no significant differences detected between the Spheramine and sham surgery arms of the study. The companies plan to fully analyze the data in order to determine a future course of action.
August 27, 2007
Biogen and Elan announced positive results from two phase III trials of Tysabri for the treatment of multiple sclerosis. These two-year, randomized, double-blind, placebo-controlled, multi-center trials, dubbed AFFIRM and SENTINEL, enrolled 2,113 subjects with relapsing multiple sclerosis. The primary endpoint was to assess the relationship between disease activity and health-related quality-of-life (HRQoL) measures in subjects treated with Tysabri compared to placebo. HRQoL was assessed using a standardized patient evaluated survey, the SF-36, which measures physical and mental components (SF-36 PCS and SF-36 MCS, respectively) and the Visual Analogue Scale (VAS). Both measurements were reviewed at weeks 24, 52 and 104. Tysabri led to statistically significant improvements in SF-36 PCS beginning at week 24 through week 104 and in SF-36 MCS at week 104, compared with a decline in the placebo group. Statistically significant improvements on the VAS were also observed over placebo at week 52 and week 104. Tysabri was recently approved by the FDA.
Eli Lilly reported positive results from a phase III trial of Cymbalta for the treatment of fibromyalgia. This randomized, placebo-controlled trial enrolled subjects with fibromyalgia, with or without depression, who received Cymbalta (60 mg or 120 mg) or placebo. They were subsequently measured at three and six months for improvements on the Brief Pain Inventory Average Pain Score (BPI) and the Patient's Global Impression of Improvement questionnaire (PGI- I). At three months, subjects in both Cymbalta arms showed significantly greater reduction in pain and improvement in PGI-I scores compared with the placebo group. In addition, more subjects treated with Cymbalta (both 60mg and 120 mg) showed significantly greater reduction in pain as measured by a 30% improvement in baseline BPI scores (50.7% and 52.1%, respectively), compared with those taking placebo (36%). At the end of the six-month trial, more subjects treated with both doses of Cymbalta showed a response to treatment, defined as a 50% reduction of baseline BPI scores, (32.6% and 35.9%, respectively), compared with subjects taking placebo (21.6%). A sNDA is currently under review by the FDA.
Merck Serono released mixed results from a phase III trial of safinamide for the treatment of Parkinsons disease. This randomized, double blind, placebo-controlled study enrolled 227 subjects with early stage Parkinsons. Of the original 227 subjects, 187 completed this 12-month extension study. The subjects were placed into one of three arms to receive safinamide 50 to 100 mg once daily, 150 to 200 mg once daily or placebo all in addition to dopamine agonist therapy. The primary objectives of the trial were long-term safety and efficacy profiles. Treatment was well tolerated, with reported adverse events similar between the safinamide and placebo groups. The primary efficacy endpoint, time to intervention, did not reach statistical significance in a pooled analysis of the safinamide arms when compared to placebo. Safinamide treatment delayed the onset of time to intervention by 93 days, as measured by the median time to the event bringing on the intervention (559 days versus 466 days; p=0.334). In a post-hoc analysis permitting an evaluation of events beyond the initial phase, subjects receiving safinamide (50 to 100mg) experienced a significantly lower rate of events compared to the subjects receiving placebo (25% versus 51%; p=0.049). A secondary efficacy endpoint was change in motor symptoms, as measured by the Unified Parkinsons Disease Rating Scale Part III Motor Score (UPDRS III). Post-hoc analysis revealed that safinamide (50 to 100 mg) added to dopamine resulted in a statistically significant improvement in motor symptoms over placebo (minus 4.79.34 versus minus 1.957.41; p=0.019). This was associated with a statistically significant improvement in quality of life, as measured by the Euro quality of life (EuroQoL), both in the pooled dose group (safinamide: 01.85, placebo: 0.421.69; p=0.0046) and in the individual dose groups (safinamide 50-100 mg: 0.031.95; p==0.017; safinamide 150-200 mg: minus 0.031.73; placebo: 0.421.69; p=0.011). Additional phase III trials are currently underway.
June 11, 2007
Faust reported positive results from a phase IIa trial of FP0011 for the treatment of Parkinson’s disease. This randomized, blinded trial enrolled 8 subjects with L-dopa-induced motor complications. Subjects were administered FP0011 or placebo over 4 cross-over periods. Treatment was well tolerated. Parkinson’s symptoms, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS), showed positive improvement. The effects were observed in three areas: "core" Parkinsonian motor symptoms, axial symptoms not sensitive to L-dopa or other dopaminergic drugs and dyskinesia. Based on these results, phase IIb trials are being planned for the near future.
April 9, 2007
GlaxoSmithKline announced positive results from a clinicaltrial of ReQuip XL 24-Hourfor the treatment of Parkinson's disease (PD). Thisdouble-blind, placebo- controlled adjunct study, dubbed EASE-PD, enrolled 393subjects with idiopathic Parkinson's disease not adequately controlled withL-dopa. Subjects were randomized 1:1 to receive ReQuip XL 24 or placebo, inaddition to L-dopa, once daily for 24 weeks. The primary endpoint was the meanchange from baseline in awake time spent 'off', defined as the return ofParkinson's symptoms as medication wears off. Secondary endpoints includedvarious motor and non-motor functions, including 'on' time. REQUIP XL 24-Hourdecreased 'off' time by an average of 2. 1 hours per day, while placebodecreased time spent 'off' by 0.3 hours per day. Treatment also significantlyincreased both 'on' time and 'on' time without troublesome dyskinesia by 1. 6hours per and reduced the percentage of 'off' time by more than 12% compared tobaseline. Based on the results, GlaxoSmithKline plans to move forward with thedevelopment of ReQuip XL 24-hour.
Opexa reported positive top-line data from a phase I/IItrial of Tovaxin for the treatment of multiple sclerosis. This one-year trialenrolled 10 subjects who received escalating subcutaneous doses of Tovaxin overa period of 20 weeks. The doses were administered at 6 - 9 x 10(6), 30 - 45 x10(6) or 60 - 90 x 10(6) attenuated T-cells. Treatment was shown to be safe andwell tolerated, with no adverse events related to T-cell vaccination. Tovaxintherapy achieved a 90% reduction in annualized relapse rate (p = 0.0039), withthe 30 - 45 x 10(6) T-cell dose group reaching a 100% reduction in annualizedrelapse rate. A phase IIb trial of Tovaxin is currently enrolling subjects.
October 23, 2006
Neurologix announced positive one year results from a phase I trial of NLX-P101, a gene therapy treatment for Parkinson's disease. This open label, dose escalating, unilateral trial enrolled 12 subjects who were placed into one of three dose-escalating cohorts. Treatment was well tolerated, with no serious adverse events reported. Efficacy results revealed that all subjects demonstrated at least a 25% improvement in the Unified Parkinson's Disease Rating Scale (UPDRS) compared to baseline (p < 0.005). Of the 12, nine had a 37% improvement and five had a 40-65% improvement. Based on the results Neurologix plans to infuse both sides of the brain in upcoming phase II trials.
October 16, 2006
Ceregene announced positive results from a phase I trial of CERE-120, a gene therapy for the treatment of Parkinson's disease. This trial enrolled 12 subjects who received CERE-120 in one of two doses. Treatment at both doses was well tolerated. The primary endpoint, reduction of symptoms as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) motor "off" score, was achieved. The subjects taking the lower dose of the drug demonstrated a 40% improvement in UPDRS motor "off" scores at 9 months, while those on the higher dose reached a similar effect at 6 months. Subjects in both treatment groups showed a 50% reduction in hours of "off" time. Based on these results, phase II trials are planned.
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.
April 24, 2006
Acadia issued positive results of a proof-of-concept trial of ACP-103, for the treatment of sleep disturbances related to Parkinson's disease and schizophrenia. This double-blind, placebo-controlled study enrolled 45 healthy adult volunteers (age 40-64), who were randomized to receive one of four doses of the drug (1 mg, 2.5 mg, 5 mg, or 20 mg) or placebo every morning for 14 consecutive days. Trial data indicated that the two higher doses of the drug significantly increased slow wave (Stage 3/4) sleep from baseline compared to placebo, both at day 1 (5 mg: +37.3 min, 20 mg: +46.0 min, vs. placebo: -11.2 min; p<0.001) and at day 13 (+41.9 min, +39.0 min, respectively, vs. -3.1 min; p<0.001). Increases in total slow-wave sleep time were seen to be dose dependent across all groups. Secondary measures also yielded positive efficacy trends, including decreases in number of awakenings (p=0.04) and time awake after sleep onset (p=0.09).
April 3, 2006
Acadia issued positive results of a phase II trial of ACP-103, for the treatment of Parkinson's disease patients with treatment-induced psychosis. This double-blind, placebo-controlled study enrolled 60 patients across sites in the US, who received once-daily doses of ACP-103 (20 mg, 40 mg or 60 mg, escalated on poor response) or placebo for 28 days, in addition to maintained stable dopamine replacement therapy. Trial data met their primary endpoint, producing no significant difference vs. placebo in motoric tolerability (no worsening of motor function on dosing), as measured on the Unified Parkinson's Disease Rating Scale (p=0.22). Secondary efficacy data were also positive, with ACP-103 producing reductions in psychotic symptom severity on two of three diagnostic measures (UPDRS Part I, p<0.05; SAPS relative change from baseline, p=0.05; SAPS total score vs. placebo, p<0.09). Also, subjects receiving the drug required fewer dose escalations than the placebo group (p<0.05), indicating efficacy at lower doses.
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.
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.
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.
February 22, 2005
Neurocrine Biosciences has issued positive results of a phase III study of indiplon MR, the long acting formulation of their non-benzodiazepine sedative for the treatment of insomnia. Results from the study met their primary efficacy endpoint, producing a significant and clinically relevant improvement in patient-reported total sleep time over the 4 weeks of treatment, versus placebo (p=0.0002). Mean increase in sleep time with indiplon was roughly one hour from baseline. No unexpected safety or tolerability concerns were raised. This randomized, double-blind, placebo-controlled, parallel-group, multi-center, out-patient study enrolled 248 patients with sleep maintenance difficulties across 50 US sites. Subjects received either 15 mg of indiplon MR tablets or placebo nightly for 4 weeks. Neurocrine anticipated including the results of this trial in their upcoming NDA submission, planned for Q2 2005.
Teva, Eisai, and H. Lundbeck have reported positive data from their phase III “PRESTO” study of Agilect (rasagiline), in the treatment of Parkinson’s disease (PD). Trial results indicated that the addition of the drug to standard optimized levodopa therapy produced significant decreases in both symptom severity and the total amount of daily time when treatment did not sufficiently ameliorate symptoms (“off” time). Specifically, patients receiving Agilect demonstrated significant improvements symptom severity score, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) and Clinical Global Improvement (CGI) scales at both trial doses, and a non-significant trend towards improvement on the PDQUALIF quality of life assessment scale at the lower trial dose. Further, the average reduction in "off" time was 1.85 hours daily for the high dose group and 1.41 hours daily in the low dose group, vs. 0.91 hours for placebo. This randomized, placebo-controlled, double-blind, parallel group study enrolled 427 moderate-to-severe PD patients on optimized levodopa therapy experiencing at least 2.5 hours of “off” time daily across 57 investigative sites in the US and Canada. Patients received one of two doses of Agilect (0.5 mg. or 1 mg.) or placebo in addition to their current therapeutic regimen. An NDA for Agilect, including these data, is currently under review by the FDA.
July 5, 2004
Amgen announced negative results of their phase II trial of their drug GDNF (glial cell line-derived neurotrophic factor), for the treatment of Parkinson's disease (PD). The drug, while safe and well tolerated, failed to meet its primary efficacy endpoint, the improvement of symptom severity score on the Unified Parkinson’s Disease Rating Scale (UPDRS). The double-blinded study enrolled 34 subjects with advanced PD, who received direct, continuous, intra-putamen infusions of either GDNF or placebo for six months. No significant difference in UPDRS score was noted between the two groups, despite measurable changes in brain function. Amgen announced that all subjects were enrolled in an open label extension study, in the hopes of resolving these results.
September 8, 2003
Teva Neuroscience reported positive results from a post-marketing trial investigating rasagiline, a (MAO-B) inhibitor for the treatment of Parkinson’s disease. Results showed that Rasagiline added to levodopa therapy reduced the total time when Parkinson’s symptoms were not adequately controlled by 1.2 hours daily or 21%. Data showed Rasagiline significantly improved motor function and activities of daily living based on the Unified Parkinson’s Disease Rating Scale. Subjects experienced more adverse events with rasagiline than with placebo which included postural hypotension only. The 18-week study enrolled 687subjects and was designed to compare the effects of once-daily rasagiline to placebo plus Comtan (entacapone). The trials were conducted in Europe, Israel, and Argentina. Results were presented at the 7th Conference of the European Federation of Neurological Societies in Helsinki.
August 11, 2003
Acadia Pharmaceuticals reported positive results from a phase I trial investigating ACP-103, a 5-HT2A inverse agonist for the treatment of various neuropsychiatric conditions. Results demonstrated that ACP-103 was safe and well tolerated with dose proportional pharmacokinetics and a long half-life. Data also demonstrated that ACP-103 was well tolerated with no changes in cardiovascular and neurological function and no serious adverse events. The randomized, double blind, placebo-controlled, dose-escalation study enrolled 49 subjects and used both single-dose and multiple-dose regimens. The single-dose study evaluated five doses ranging from 20 to 300 mg and the multiple dose-escalation study evaluated oral doses of 50, 100, and 150 mg given once-daily for 14-days.
January 13, 2003
Newron reported positive preliminary results from a phase II trial investigating safinamide, a possible neuroprotectant for the treatment of Parkinson's disease. Data showed that subjects who were administered safinamide with dopamine agonist therapy exhibited a 30 % reduction in motor scores. Results demonstrated that the treatment of safinamide (1.0 mg/kg/die) resulted in a statistically significant improvement, defined as at least 30% reduction of the UPDRS III motor scores, in those subjects who were treated with a steady dose of a dopamine agonist. Safinamide was found to be very safe in all subjects. The multinational, double blind, parallel study enrolled 151 subjects with Parkinson's disease. Subjects were given safinamide (0.5 - 1.0 mg/kg) in a once a day schedule or placebo for three months.
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.
April 29, 2002
Results from a 12-month, open-label, six-subject phase I/II trial indicate that Spheramine improves motor function in subjects with advanced Parkinson's disease. Subjects were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) pre- and post-treatment, both 'on' and 'off' their normal medication. According to the trial data, subjects experienced an almost 50% improvement in motor function with Spheramine treatment. An average 43% improvement was observed in total UPDRS score, in addition to improvements in quality of life and activities of daily living. Spheramine is being developed by Titan and Schering AG.
April 22, 2002
Results from a multicenter, double-blind phase II trial suggest that Guilford Pharmaceuticals' GPI-1485 may delay the loss of dopamine transporters in subjects with mild-to-moderate Parkinson's disease. Three hundred subjects were randomized to receive placebo, low-dose GPI-1485 or high-dose GPI-1485 administered orally for 24 weeks. Change in dopamine transporter density was measured utilizing Dopascan Injection and single photon emission computed tomography (SPECT). SPECT brain scans were obtained for 105 subjects at baseline and six months after randomization. According to a second evaluation of the SPECT scores, the mean percent change from baseline in the density of dopamine nerve terminals was -2.4% in the placebo group, -3.5% in the low-dose group and +1.6% in the high-dose group.