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Fibromyalgia

July 11, 2011

Pfizer Japan issued preliminary results from a phase III trial of pregabalin for the treatment of fibromyalgia. This 16-week, randomized, double-blind, placebo-controlled, parallel group, multi-center study enrolled 501 subjects and compared pregabalin flexibly dosed (300-450 mg/day, twice-daily) and placebo. The primary endpoint was reached, with results demonstrating a statistically significant reduction in the mean pain score when compared to placebo. The most common adverse events were somnolence, dizziness, weight increased, constipation, feeling abnormal, edema peripheral and blurred vision.

June 22, 2009

Jazz Pharmaceuticals issued positive results from a phase III trial of sodium oxybate (JZP-6) for the treatment of fibromyalgia. This randomized, double-blind, placebo-controlled study enrolled 548 adult subjects who received sodium oxybate 4.5 g/night, sodium oxybate 6 g/night or placebo. The primary endpoint was the proportion of subjects who achieved at least 30 percent reduction in pain from baseline to endpoint based on the Pain Visual Analog Scale (VAS). Three month data showed that 54.2% and 58.5% of subjects treated with sodium oxybate 4.5 g/night and 6 g/night, respectively, showed significantly greater reduction in pain (VAS score), compared with 35.2% of subjects taking placebo (p<0.001). Both doses of sodium oxybate resulted in significant reductions in fatigue as early as Week 1 after dosing compared with placebo, as measured by the Fatigue VAS (p<0.001); these results were maintained through 14 weeks (p<0.009). In addition, when compared to placebo both doses of sodium oxybate showed significant improvement in sleep patterns as measured by the Jenkins Sleep Scale (p<0.001), statistically significant improvements in mean scores on the Fibromyalgia Impact Questionnaire, a measure of daily function, and on Patient Global Impression of Change. Treatment was well tolerated in this population.

December 1, 2008

Jazz Pharmaceuticals issued positive preliminary results from a phase III trial of sodium oxybate (JZP-6) for the treatment of fibromyalgia. This randomized, double-blind, placebo-controlled study enrolled 548 adult subjects. The subjects were placed in one of three treatment arms and received sodium oxybate 4.5 g/night, sodium oxybate 6 g/night or placebo. The primary endpoint was the proportion of subjects who achieved at least 30 percent reduction in pain from baseline to endpoint based on the Pain Visual Analog Scale (VAS). This endpoint was reached; 46.2% and 39.3% of subjects on 4.5 g/night and 6 g/night, respectively, reported this level of pain relief, compared with 27.3% of those on placebo. Physical functioning and ability to perform daily tasks, as measured by the Fibromyalgia Impact Questionnaire, were significantly different from placebo for the 4.5 g/night dose and approached significance for the 6 g/night dose. In addition, a significant improvement in fatigue was reported for both active dosage levels. Sodium oxybate was generally well tolerated.

July 14, 2008

Antisense Therapeutics and Teva reported positive results from a phase IIa trial of ATL1102 for the treatment of multiple sclerosis. This randomized, double-blind, placebo-controlled study enrolled 77 subjects with relapsing, remitting multiple sclerosis, in Europe. The subjects received either ATL1102 or placebo injections subcutaneously at a dose of 200 mg three times a week for the first week, then twice weekly over seven additional weeks. They were subsequently monitored for an additional eight weeks. The primary endpoint was a reduction in cumulative number of new active lesions compared to placebo, measured via monthly magnetic resonance images (MRI) brain scans. ATL1102 showed a significant 54.4% reduction in cumulative number of new active MRI esions on weeks 4, 8 and 12 (p=0.01). In addition, ATL1102 led to a 65% reduction in cumulative number of Gadolinium (Gd)-enhancing lesions on weeks 4, 8, and 12 (p=0.0053). It was also effective in significantly reducing T1-enhancing lesion volume by 84% at week 12. Treatment was well tolerated. Based on the results the development of ATL1102 will move forward.

UCB Pharma released mixed results from a phase IIa trial of lacosamide for the treatment of fibromyalgia syndrome. This randomized, placebo-controlled, double-blind trial enrolled 158 subjects who received lacosamide 400 mg per day. The primary endpoint was a within-subject change in average daily pain score from baseline to the last two weeks of the treatment phase using an 11-point Likert scale. This endpoint was reached, with an effect size of 0.5 in favor of lacosamide versus placebo. Treatment was generally well tolerated. UCB plans to fully analyze the data and make a decision regarding phase IIb trials by the end of the year.

November 19, 2007

Cypress and Forest issued positive composite responder results two phase III trials of milnacipran for the treatment of fibromyalgia. Study MLN-MD-02 was a double-blind, placebo-controlled design and enrolled 1,196 subjects who were randomized to receive either milnacipran 100 mg/day, 200 mg/day or placebo over a three-month period. Study FMS-031 was a double-blind, placebo-controlled trial and enrolled 888 subjects who were randomized to receive either milnacipran 100 mg/day, 200 mg/day or placebo for six months To be considered a responder for the composite "pain of fibromyalgia" endpoint, each subject had to demonstrate concurrent and clinically meaningful improvements in two validated measures: pain and global impression of disease status. Pain composite responders were defined as individuals who achieved both a greater than or equal to 30% reduction in pain from baseline and who rated themselves as "very much improved" or "much improved" on a Patient Global Impression of Change (PGIC) scale. To be considered a composite responder for the "treatment of the fibromyalgia syndrome" endpoint subjects had to demonstrate improvement in a third validated measure: physical function. Fibromyalgia syndrome composite responders needed to satisfy the pain composite criteria as well as demonstrate at least a 6-point improvement in their SF-36 physical component summary (SF-36 PCS) score. In study MLN-MD-02 there were 713 evaluable subjects for the fibromyalgia syndrome and pain analyses. In study FMS-031 there were 488 evaluable subjects for the fibromyalgia syndrome analysis and 491 evaluable subjects for the fibromyalgia pain analysis. A statistically significant number of subjects treated with milnacipran during Study MLN-MD-02 met the composite syndrome responder criteria: 25% and 26% for the milnacipran 100 mg and 200 mg groups compared to 13% for placebo. A statistically significant number of subjects treated with milnacipran during Study FMS-031 met the composite syndrome responder criteria at six months: 33% and 32% for the milnacipran 100 mg and 200 mg groups, respectively, compared to 19% for placebo. The composite pain responder criteria for fibromyalgia pain also reached statistical significance during Study MLN-MD-02: 39% and 46% in the milnacipran 100 mg and 200 mg groups, respectively compared to 25% for placebo. A statistically significant number of subjects treated with milnacipran during Study FMS-031 also met these criteria at six months: 44% and 45% of subjects in the milnacipran 100 mg and 200 mg groups, respectively, compared to 28% for placebo. Based on positive phase III results, Cypress and Forest planned to file an NDA around the end of 2007.

Schering Plough and Centocor reported positive results from a phase III trial of golimumab for the treatment of psoriatic arthritis. This study, dubbed GO-REVEAL (Golimumab - A Randomized Evaluation of Safety and Efficacy in Subjects with Psoriatic Arthritis Using a Human Anti-TNF Monoclonal Antibody), enrolled 405 adult subjects with psoriatic arthritis. The subjects were randomized to receive subcutaneous (SC) injections of placebo or golimumab (50 or 100 mg) at weeks zero, four, eight, twelve, sixteen and twenty. At week sixteen, subjects with inadequate arthritis response were switched to golimumab 50 mg (those originally receiving placebo) or golimumab 100 mg (those originally receiving golimumab 50 mg). The primary endpoint was at least a 20 percent improvement in arthritis signs and symptoms (ACR 20) response at week fourteen for combined golimumab groups and individual golimumab dose groups versus placebo. At week fourteen, 51% of subjects receiving golimumab 50 mg and 45% of subjects receiving golimumab 100 mg experienced ACR 20 compared with 9% of subjects receiving placebo (p less than 0.001). These improvements were maintained through week twenty-four, with 52% and 61% of subjects receiving golimumab 50 mg and golimumab 100 mg, respectively, reaching ACR 20, compared with 12% of subjects receiving placebo (p less than 0.001). Significant improvements were observed in other key endpoints including ACR 50 and ACR 70 and improvements in enthesitis and dactylitis ((p less than 0.001). Among a subset of subjects with at least three percent of body surface area involved by psoriasis at baseline, 40% and 58% of subjects in the golimumab 50 mg and golimumab 100 mg, respectively, achieved PASI 75 at week fourteen, compared with 3% of subjects receiving placebo (P less than 0.001). At week twenty-four, PASI 75 improved to 56% and 66% (golimumab 50 mg and 100 mg, respectively) compared with 1% for placebo (p less than 0.001). In addition, the subjects were classified as good or moderate responders as measured by the Disease Activity Score 28 (DAS28). At week fourteen, 66% and 67% of subjects in the golimumab 50 mg and 100 mg arms, respectively, were DAS28 responders, compared with 24% of subjects in the placebo arm (p less than 0.001). At week twenty-four, this improved to 64% and 78% for golimumab 50 mg and 100 mg, respectively, compared with 24% for the placebo group (p less than 0.001). Additional phase III trials are ongoing at this time.

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.

May 28, 2007

Cypress and Forest Labs announced positive preliminary top-line results from a phase III trial of milnacipran for the treatment of fibromyalgia syndrome. This randomized, double-blind, placebo-controlled trial enrolled 1,196 subjects who received milnacipran (200 or 100 mg per day) or placebo for three months. The primary endpoints were composite responder assessments to evaluate either 1) the treatment of the pain associated with fibromyalgia syndrome or 2) the overall treatment of fibromyalgia syndrome. Statistically significant improvement was seen in the first primary endpoint compared to placebo for subjects receiving both the 200 mg per day dose (p=0.004) and the100 mg per day dose (p=0.025). Statistically significant improvement compared to placebo was observed in the second endpoint as well for both the 200 mg per day dose (p=0.015) and 100 mg per day dose (p=0.011). Based on the positive results, the companies plan to submit a NDA to the FDA near the end of 2007.

November 21, 2005

Biogen Idec issued positive results of a phase II trial of Amevive (alefacept) for the treatment of psoriatic arthritis (PA). Amevive is currently approved to treat psoriasis. Trial results indicated that 54% of subjects receiving the drug achieved ACR20 response, vs. 23% of subjects receiving placebo (p<0.001). 17% achieved ACR50 and 7% achieved ACR70 with Amevive, vs. 10% and 2% respectively for placebo. Improvements in tender-joint (31% vs. 18%) and swollen-joint count (46% vs. 34%) were also noted. This randomized, double-blind, placebo- controlled study enrolled 185 PA patients, who received standard therapy with methotrexate plus Amevive (n=123) or placebo (n=62).

Jazz Pharmaceuticals announced positive results of a phase II trial of Xyrem (sodium oxybate) for the treatment of fibromyalgia. Xyrem is currently approved for the treatment of narcolepsy. Results from the study indicated that both the low and high dose regimens of the drug produced significant reductions in composite primary outcome variable (including Pain Visual Analog Scale, Fibromyalgia Impact Questionnaire, and Patient Global Impression of Change) compared to placebo: 34.5% in the low dose group (p=0.005) and 27.3% (p=0.048) achieved significant improvement in this measure, vs. 12.5% for placebo. Treatment was generally well tolerated. This randomized, double-blind, placebo-controlled study enrolled 188 patients, who received one of two daily doses of Xyrem (4.5g or 6g) or placebo for 8 weeks, taken in two divided doses (first at bedtime, second 2.5 to 4 hours later).

Savient issued positive results of a phase II trial of Puricase (PEG-uricase) for the treatment of refractory gout. This randomized, open label, multicenter, parallel group study enrolled 41 patients, who received one of 4 regimens of the drug (4 mg every 2 weeks, n=7; 8 mg every 2 weeks, n=8; 8 mg every 4 weeks, n=13; 12 mg every 4 weeks, n=13). The drug was shown to reduce plasma urate levels at all trial doses (from 7.56 mg/dL to 4.20; from 9.09 to 1.42; from 9.08 to 2.57; and from 8.47 to 2.60, respectively). The doses also maintained urate levels below 6 mg/dL for 73%, 92% 86% and 84% of the time. There were 5 serious adverse events reported, including gout flare (n=3), hypersensitivity reaction (n=1), and anemia (n=1).

October 3, 2005

Forest Laboratories and Cypress Bioscience reported negative top-line results of a phase III trial of milnacipran for the treatment of fibromyalgia (FMS). Preliminary data did not meet their primary efficacy endpoint, with overall improvement in symptom severity (as measured by Last Observation Carry-forward (LOCF) analysis of Patient Experience Diary and Patient Global Impression of Change assessments) showing a positive trend but failing to achieve statistical significance at 3 months (p=0.058). Secondary examination of both assessments via Baseline Observation Carry-forward (BOCF) analysis did achieve statistical significance at 3 months (p=0.048), but this was potentially insufficient as a registration endpoint. Data for both LOCF and BOCF were positive-trending but non-significant at 6 months as well (p=0.057 and p=0.067, respectively), as was the result for a composite analysis of the primary endpoints plus physical functional assessment at both 3 and 6 months. This randomized, double-blind, placebo-controlled pivotal study enrolled 888 FMS patients, who received 200 mg milnacipran or placebo daily for 6 months. The companies indicated that they viewed these data as supportive of both their ongoing and planned phase III studies of the drug.

February 24, 2003

Cypress Bioscience reported positive results from a phase II trial investigating milnacipran, a norepinephrine serotonin reuptake inhibitor for the treatment of Fibromyalgia Syndrome. Results showed that 70% of subjects treated with milnacipran reported overall improvement in pain compared to 36% of subject treated with placebo. Data showed that 37% of subjects treated with milnacipran reported at least a 50% reduction in pain intensity compared to 14% of subjects given placebo. In addition, subjects treated with milnacipran showed improvements in fatigue and depressed mood. The double blind, placebo controlled, dose escalating study enrolled 125 subjects with Fibromyalgia Syndrome. Subjects were administered either placebo or milnacipran (once or twice per day) for four weeks of dose escalation followed by eight weeks of constant dose.