Milnacipran Safe, Effective for Long-Term Treatment of Fibromyalgia

Jenny Ko, PharmD

May 20, 2011

 

AUSTIN, TX—Sustained long-term efficacy and tolerability of milnacipran—in some cases, exceeding three years of continuous usage—is supported in the treatment of patients with fibromyalgia, according to results of an open-label study presented during the American Pain Society's 30th Annual Scientific Meeting.

Fibromyalgia is a chronic disorder characterized by widespread pain and other symptoms that adversely impact function and health-related quality of life. For that reason, durable efficacy is an important treatment goal, noted Lesley Arnold, MD, from the University of Cincinnati College of Medicine, Cincinnati, OH, and colleagues.
To determine long-term efficacy of milnacipran, which is approved for the management of fibromyalgia, treatment effects were evaluated in 1,227 patients in a safety and efficacy study over a period that could exceed three years. Eligible patients were those with fibromyalgia who had successfully completed previous studies of milnacipran. The multicenter, open-label, flexible-dose study comprised a two-week washout period, a two-week dose-escalation period (to milnacipran 100mg/day), an 8-week stable-dose period (at milnacipran 100mg/day), and a flexible-dose period (milnacipran 50–200mg/day) for the remainder of the study. Key efficacy outcomes included 24-hour visual analog scale (VAS) and weekly recall pain (0–100 scale), Patient Global Impression of Change (PGIC), Patient Global Disease Status (PGDS), SF-36 Physical Component Summary (SF-36 PCS), and the Brief Pain Inventory (BPI).
Of the 1,227 patients, 47.7% were considered completers; 206 patients reached the final visit and 379 were enrolled when the study was terminated. Efficacy results were reported as mean changes from study baseline following the two-week washout period. At the final visit, patients treated with milnacipran demonstrated a mean (SEM) improvement from baseline in 24-hour VAS recall pain scores of 23.1 points (1.82) (observed cases). Improvements in VAS weekly recall pain, BPI scores, global status (PGIC, PGDS), and physical function (SF-36 PCS) were all observed with milnacipran treatment.
Over the three-year study, the most common treatment-emergent adverse events were nausea (25.9%), headache (13.4%), hypertension (11.2%), and sinusitis (10.4); 20.9% of patients discontinued the study due to these events, primarily nausea.

http://www.clinicaladvisor.com/milnacipran-safe-effective-for-long-term-treatment-of-fibromyalgia/article/203390/

GW Pharmaceuticals and Sativex

17 May 2011 GW Pharmaceuticals, the Cambridge pharma company marketing drugs based on cannabis, has turned a £2.7m loss last time into a net pre-tax profit of £3.1m in the six months to March 31.
The turnround was spurred by an upsurge in total revenues, which increased 45 per cent to £16.6m (H1 2010: £11.4m) including milestone receipts of £5.1m (£nil) and increased Sativex sales of £1.9m (£0.9m).
Cash and short term deposits at period-end increased to £28.3m (£20.4m).
GW’s lead product, Sativex, is a cannabinoid mouth spray identical to whole-plant marijuana in liquid form and was developed for multiple sclerosis patients, who can use it to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms.
Sativex is also being prescribed to alleviate pain due to cancer and has been researched in various models of peripheral and central neuropathic pain.
During the half-year, a licence agreement was signed with Novartis to commercialise Sativex in Australasia, Asia (excluding Japan/China), the Middle East (excluding Israel) and Africa.
It has been recommended for approval in Germany, Italy, Denmark, Sweden, Austria and the Czech Republic. Launches are expected this year in Germany, Denmark and Sweden following launch in Spain in March.
The US is a massive potential market for the company: A Phase III cancer pain programme is underway, fully funded by US partner, Otsuka.

Two Phase IIa clinical trials of novel cannabinoid medicine in diabetes and metabolic disease have also begun.

Positive pre-clinical data in epilepsy, glioma, breast cancer and other conditions continue to be generated as part of Otsuka research collaboration.
Dr Geoffrey Guy, GW’s chairman, said: “GW has delivered another robust set of financial results, with substantially increased revenues yielding a profit for the period and a strong cash position.
“With Sativex now launched in the UK and Spain, an increasing number of additional European approvals and launches for Sativex now expected and the recent agreement with Novartis to commercialise Sativex across a broad region of the world, Sativex should provide GW with a platform for significant growth in the coming years.

“In parallel we have embarked on a substantial Phase III programme for Sativex in cancer pain, a major market opportunity, a Phase II clinical programme for a novel cannabinoid medicine in diabetes and we continue to generate highly promising data in our earlier stage pipeline.
“With regular Sativex launches now taking place, GW has entered a new phase in the evolution of the company and we believe that our prospects for commercial success with Sativex together with a highly promising and maturing pipeline provide confidence for the remainder of 2011 and beyond.”
http://www.businessweekly.co.uk/biomedtech-/11836-cannabis-company-up-to-speed-as-cash-starts-to-flow

Acadia Pharma awarded grant from NIH for development of novel ER-beta agonists

Acadia Pharmaceuticals Inc. a biopharmaceutical company utilizing innovative technology to fuel drug discovery and clinical development of novel treatments for central nervous system disorders, announced that it has been awarded a grant from the National Institute of Neurological Disorders and Stroke (NINDS), a division of the National Institutes of Health (NIH), for the development of novel Estrogen Receptor beta (ER-beta) agonists for the treatment of neuropathic pain. The grant provides funding of up to $2.4 million and was awarded under the NINDS Fast-Track Small Business Innovative Research Co-operative Programme in Translational Research that supports the identification and preclinical testing of new therapeutics for neurological disorders.

“We are delighted to be awarded this NINDS grant, which allows us to advance our promising ER-beta program in the area of neuropathic pain and provides important recognition of our scientific discoveries,” said Uli Hacksell, PhD, chief executive officer of Acadia. “Our ER-beta compounds also offer the potential for an innovative disease-modifying approach to the treatment of Parkinson's disease, and our initial studies in this area have been supported by grants from The Michael J Fox Foundation.”

Studies have shown that estrogen modulates many cerebral functions such as mental state, mood, cognition and perception of pain. Estrogen stimulates both ER-alpha and ER-beta receptors. Acadia researchers have identified novel and selective ER-beta agonists that may address the symptoms of chronic, inflammatory and neuropathic pain while avoiding the side effects associated with activating ER-alpha receptors. Pursuant to the grant, Acadia will initially examine the efficacy of selected proprietary ER-beta compounds in preclinical models and intends to subsequently conduct preclinical development studies required in support of potential future clinical studies.

Neuropathic pain is a debilitating disorder caused by damage or dysfunction of the nervous system and originates from many diverse sources including diabetic and hereditary neuropathies, herpes, chemotherapy, physical traumas and surgery. Current first-line medications are limited by variable efficacy and adverse effects. There is a major unmet medical need for novel, safe and effective drugs to treat neuropathic pain.

LYRICA: Pfizer sales report

May 03, 2011 : Kevin Grogan
Pfizer has reported flat sales for the first quarter while net income rose 10% to $2.22 billion, beating analyst estimates.
Lyrica, Prevnar on the rise

Sales of Lyrica (pregabalin), for epilepsy, fibromyalgia and neuropathic pain, increased 14% to $826 million,


As for products Pfizer got hold of through its acquisition of Wyeth, the antidepressant Effexor (venlafaxine) contributed just $204 million, down 72% as a result of generic competition,


Chief executive Ian Read said he was pleased "not only with our solid financial performance during the first quarter despite the loss of exclusivity of several products in the USA and other geographies, but also with our ability to enhance shareholder value through various initiatives", notably a share repurchase programme. He added that Pfizer's emerging markets unit delivered 8% operational growth, "driven by many of our priority countries, notably China, and continued to benefit from our ongoing targeted investment".
http://www.pharmatimes.com/Article/11-05-03/Healthy_quarter_for_Pfizer_no_news_of_further_sell-offs.aspx

EXERCISE: Virtual reality exposure therapy as treatment for pain catastrophizing in fibromyalgia patients: proof-of-concept study

Author: Linzette MorrisKaren Grimmer-SomersBruce SpottiswoodeQuinette Louw
Credits/Source: BMC Musculoskeletal Disorders 2011, 12:85

Albeit exercise is currently advocated as one of the most effective management strategies for fibromyalgia syndrome (FMS); the implementation of exercise as a FMS treatment in reality is significantly hampered by patients'poor compliance. The inference that pain catastrophizing is a key predictor of poor compliance in FMS patients, justifies considering the alteration of pain catastrophizing in improving compliance towards exercises in FMS patients.
The aim of this study is to provide proof-of-concept for the development and testing of a novel virtual reality exposure therapy (VRET) program as treatment for exercise-related pain catastrophizing in FMS patients.

Methods:
Two interlinked experimental studies will be conducted. Study 1 aims to objectively ascertain if neurophysiological changes occur in the functional brain areas associated with pain catastrophizing, when catastrophizing FMS subjects are exposed to visuals of exercise activities.
Study 2 aims to ascertain the preliminary efficacy and feasibility of exposure to visuals of exercise activities as a treatment for exercise-related pain catastrophizing in FMS subjects. Twenty subjects will be selected from a group of FMS patients attending the Tygerberg Hospital in Cape Town, South Africa and randomly allocated to either the VRET (intervention) group or waiting list (control) group.
Baseline neurophysiological activity for subjects will be collected in study 1 using functional magnetic resonance imaging (fMRI). In study 2, clinical improvement in pain catastrophizing will be measured using fMRI (objective) and the pain catastrophizing scale (subjective).DiscussionThe premise is if exposing FMS patients to visuals of various exercise activities trigger the functional brain areas associated with pain catastrophizing; then as a treatment, repeated exposure to visuals of the exercise activities using a VRET program could possibly decrease exercise-related pain catastrophizing in FMS patients.
Proof-of-concept will either be established or negated. The results of this project are envisaged to revolutionize FMS and pain catastrophizing research and in the future, assist health professionals and FMS patients in reducing despondency regarding FMS management.
Trial registration: PACTR201011000264179
http://7thspace.com/headlines/380906/virtual_reality_exposure_therapy_as_treatment_for_pain_catastrophizing_in_fibromyalgia_patients_proof_of_concept_study_study_protocol.html

Cymbalta approved by Health Canada for low back pain

TORONTO, April 29 /CNW/ - Eli Lilly Canada announced today that Health Canada has approved Cymbalta^® (duloxetine HCl) for the management of chronic low back pain (CLBP).  The recommended dose is 60 mg once daily.
The approval is based on the results of two randomized, double-blind, 12-13 week, placebo-controlled studies in 637 adult patients with a clinical diagnosis of CLBP with pain present on most days for at least 6 months and no sign of radiculopathy or spinal stenosis.¹ The primary efficacy endpoint in both studies was a reduction in pain severity as measured by the Brief Pain Inventory (PBI) 24-hour average pain rating on the 11-point Likert scale (0 = no pain; 10 = worst possible pain). In both studies, patients taking Cymbalta 60 mg once daily experienced significantly greater pain reduction compared to placebo.  In addition, some patients reported pain reduction as early as one week into the trial after starting the 60 mg dose, which continued throughout the study.
Cymbalta has been evaluated for safety in 698 patients with CLBP. The most common side effects reported in the two studies included nausea, insomnia, somnolence, constipation, dry mouth, fatigue and dizziness.¹

About Cymbalta
Cymbalta is a potent and balanced serotonin and norepinephrine reuptake inhibitor (SNRI), which targets two chemical messengers in the brain believed to play a role in sensitivity to pain - serotonin and norepinephrine. While the mechanism of action of duloxetine in humans is not fully known, scientists believe its effect on pain perception is due to increasing the activity of serotonin and norepinephrine in the central nervous system.

Cymbalta is now indicated in Canada for three distinct pain conditions: CLBP, neuropathic pain associated with diabetic peripheral neuropathy and fibromyalgia.  It is also indicated in Canada for the symptomatic relief of major depressive disorder (MDD) and generalized anxiety disorder (GAD).
Duloxetine is contraindicated in patients who are allergic to it, who have liver disease resulting in hepatic impairment, who are taking a monoamine oxidase inhibitor (MAOI) including linezolid and methylene blue, thiorazidine, potent CYP1A2 inhibitors (e.g. fluvoxamine), and some guinolone antibiotics (e.g. ciprofloxacin or enoxacine), who have uncontrolled narrow glaucoma, or who have severe kidney disease.
About Lilly
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Indiana, Lilly provides answers - through medicines and information - for some of the world's most urgent medical needs.  Eli Lilly Canada, headquartered in Toronto, Ontario, employs close to 500 people across the country.  Additional information about Eli Lilly Canada can be found at http://www.lilly.ca/.

^® Registered trademark owned by Eli Lilly and Company; used under license.

http://www.digitaljournal.com/pr/292994#ixzz1LEEk6UYb

Cymbalta generic version blocked

Associated Press, 04.27.11,

INDIANAPOLIS -- Eli Lilly and Co. said Wednesday that a federal court is blocking low-cost generic versions of Cymbalta from the market until the patents supporting the drug expire.

Eli Lilly  said the order from the U.S. District Court for the Southern District of Indiana will stop generic competition for Cymbalta, Lilly's second best-selling drug, until at least June 2013. The company said the court initially entered a judgment in its favor on March 21. As part of Wednesday's ruling, the defendants are required to inform the Food and Drug Administration that they are not seeking approval for generic Cymbalta until the patents expire.

Eli Lilly said the litigation has been dismissed and no appeal is possible.

Cymbalta, or duloxetine, is approved to treat depression, fibromyalgia and musculoskeletal pain. The company reported $2.77 billion in U.S. sales in 2010. That was 80 percent of worldwide Cymbalta sales, which totaled $3.48 billion.
http://www.forbes.com/feeds/ap/2011/04/27/business-health-care-us-eli-lilly-cymbalta_8438430.html

Eli Lilly and Cymbalta

Eli Lilly has posted a 15% decline in earnings for the first quarter, but sales were up 6%, with the antidepressant/fibromyalgia blockbuster Cymbalta and the lung cancer drug Alimta once again driving sales.

The most striking performance came from Cymbalta (duloxetine), up 13% to $908.8 million, Lilly’s best-selling drug continues to be the antipsychotic Zyprexa (olanzapine).

 http://www.pharmatimes.com/Article/11-04-19/Lilly_profits_hit_by_Boehringer_charge_good_sales_rise.aspx

Forest Laboratories, Inc and Savella

Forest Laboratories, Inc. 
The Quarter in Detail
Savella, which is approved for the management of fibromyalgia, posted sales of $23.7 million, up significantly from the year-earlier sales of $17.4 million.
Savella was launched in late April 2009. We believe the product may have multi-hundred million dollar potential.
In early October 2010, Savella was moved into tier II unrestricted coverage on several managed care organizations. Improved formulary access should help boost sales. Forest Labs entered into a collaboration and distribution agreement with Janssen to commercialize Savella in Canada.
 Savella sales are expected to grow 31%.
http://www.zacks.com/stock/news/51551/Forest+Tops+Again,+Provides+Outlook+

Chelsea Therapeutics and Droxidopa

Chelsea Therapeutics will seek federal approval for its blood pressure drug.
Northera is designed to treat neurogenic orthostatic hypotension, which is a drop in blood pressure. The product is Chelsea's lead drug candidate and the company does not yet have a product on the market.
Chelsea Therapeutics International Ltd. has previously said it hopes to launch the drug in early 2012. Meanwhile, the company will continue to study the drug as a potential treatment for neurogenic orthostatic hypotension from Parkinson's Disease.
The active ingredient in Northera is droxidopa and Chelsea is also studying droxidopa as a treatment for fibromyalgia, a chronic disease that causes muscle pain and fatigue.
http://www.businessweek.com/ap/financialnews/D9MM7E2G0.htm

Fibromyalgia and obesity: the hidden link

Rheumatology International : Francesco Ursini, Saverio Naty and Rosa Daniela Grembiale

 

Fibromyalgia is a chronic disorder of uncertain etiology, characterized by widespread pain, muscle tenderness, and decreased pain threshold to pressure and other stimuli. Obesity is a well-known aggravating factor for certain rheumatologic conditions, such as knee osteoarthritis. Emerging evidences are exploring the link between obesity and other rheumatic diseases, such as fibromyalgia. Epidemiological data show that fibromyalgia patients have higher prevalence of obesity (40%) and overweight (30%) in multiple studies compared with healthy patients. Several mechanisms have been proposed to explain “the hidden link”, but at this time is not possible to ascertain whether obesity is cause or consequence of fibromyalgia. Among mechanisms proposed, there are the following: impaired physical activity, cognitive and sleep disturbances, psychiatric comorbidity and depression, dysfunction of thyroid gland, dysfunction of the GH/IGF-1 axis, impairment of the endogenous opioid system. In this article, we review the scientific evidence supporting a possible link between obesity and fibromyalgia, how obesity influences fibromyalgia symptoms and how fibromyalgia severity can be improved by weight loss. In addition, we analyze the possible mechanisms by which fibromyalgia and obesity interrelate.

http://www.springerlink.com/content/h656n0555r763146/

Balneotherapy in fibromyalgia: A single blind randomized controlled clinical study

Rheumatology International, 04/11/2011  Clinical Article

Özkurt S et al. – It was concluded that balneotherapy provides beneficial effects in patients with fibromyalgia.
Methods

• 50 women with fibromyalgia under pharmacological treatment randomly assigned to either balneotherapy (25) or control (25) group
• 4 patients from balneotherapy group and 1 patient from control group left study after randomization
• Patients in balneotherapy group (21) had 2 thermomineral water baths daily for 2 weeks in Tuzla Spa Center
• Patients in control group (24) continued to have medical treatment and routine daily life
• Investigator blinded to study arms assessed patients
• All patients assessed 4 times; at beginning, at end of 2nd week, 1st month, and 3rd month after balneotherapy
• Outcome measures were pain intensity, Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), patient’s global assessment, investigator’s global assessment, SF-36 scores, and tender point count

Results

• Balneotherapy found to be superior at end of cure period in terms of pain intensity, FIQ, Beck Depression Inventory, patient’s global assessment, investigator’s global assessment scores, and tender point count as compared to control group
• Superiority of balneotherapy lasted up to end of 3rd month, except for Beck Depression Inventory score and investigator’s global assessment score
• Significant improvements observed in PF, GH, and MH subscales of SF-36 during study period in balneotherapy group
• No improvement observed in control group
• Balneotherapy superior only in VT subscale at end of therapy and at end of third month after therapy as compared to controls

Social Security Disability And Fibromyalgia

In Fibromyalgia claims the clinical notes and a report of the treating rheumatologist are most important. A 1996 decision by the Seventh Circuit Court of Appeals established that a rheumatologist is the primary source for proof of this disease. Office notes from the rheumatologist should consistently document the positive findings for the tender points which are diagnostic for this disease. In addition, the patient should be complaining at each office visit of the fatigue and pain that are consistent with this condition. A report that establishes that all other causes for the symptoms have been ruled out helps establish the existence of the disease.
Since the extent of fatigue and pain can not be measured, consistency of complaints in the various medical records will be important. The use of pain medications, even if just for trial periods is an important consideration in evaluating the severity of pain. Use of mild analgesics indicates less severe symptoms; prescription of stronger narcotics indicates that the treating specialist felt the pain problems more severe. Also, documentation by the physicians of concentration impairments, and the inability to perform routine daily activities such as housework, shopping, and social functioning, are also factors considered by Social Security Administration decision makers.
http://autoinsurancepaylittle.com/social-security-disability-and-fibromyalgia/

Antiepileptic Drugs for Fibromyalgia Reviewed

April 8, 2011

Fibromyalgia syndrome (FMS) is a difficult-to-treat chronic pain condition with relatively few specifically approved and effective pharmacotherapies. A recent review examined the relative benefits and harms of pregabalin, the only antiepileptic FDA approved for fibromyalgia, and the antiseizure medication gabapentin in the treatment of FMS. However, the evidence supporting their efficacy was somewhat disappointing.
Writing in the Journal of Pain, researchers from the Oregon Health & Science University, School of Medicine, Portland, Oregon, report conducting an extensive literature search for studies of any antiepileptic drug compared with placebo or another antiepileptic agent in a randomized controlled trial (RCT) or observational study [Siler et al. 2011]. Only 8 studies were discovered matching those inclusion criteria: 7 of pregabalin (Lyrica®) that included 2,964 subjects total, and 1 trial of gabapentin (eg, Neurontin® and generics) that enrolled 150 participants. Populations studied included predominantly women aged 47 to 50 years.
Short-term (8-14 weeks), response rates with both drugs at various doses, and reducing mean pain scores by 30% from baseline, were modestly greater than placebo — pregabalin 26% to 50%; gabapentin up to a 51%; compared with 19% to 35% response rates with placebo. [Note: these data are taken from body text of article, which differs from the abstract.] Study withdrawals due to adverse events were significantly greater in pregabalin groups compared with placebo, with relative risks increasing as dose was increased. Gabapentin had similar drop-out rates but not statistically different from placebo (possibly due to the small sample size in this trial).

Compared with placebo, both drugs had greater rates of side effects. Dizziness, headache, somnolence, and edema were the most commonly reported adverse events for both drugs. Dizziness was most common with pregabalin (38%), while headache (27%) was more prevalent with gabapentin. Additionally, weight gain was more common with pregabalin than placebo, whereas sedation and light-headedness occurred more often with gabapentin than placebo.
A follow-up analysis found that about 25% of the pain relief associated with pregabalin was significantly correlated with combined improvements in anxiety and depression. Examination of the impact of other factors such as age, race, gender, and socioeconomic status on the benefits or harms associated with pregabalin or gabapentin was not possible due to narrow inclusion criteria and limited reporting in the studies.
There were important methodological differences between the pregabalin and gabapentin trials and, without head-to-head clinical studies, the authors state it is not possible to conclude if pregabalin or gabapentin is superior. While it appeared that gabapentin was slightly more efficacious, the drug incurred significantly higher rates of headache than pregabalin and it was studied in only a single, small-scale RCT.
The authors believe that results of their review indicate that pregabalin and gabapentin can be used for the treatment of fibromyalgia with moderate benefits in the short-term. However, clinicians must be cautious not to generalize these results to other, unstudied antiepileptic drugs, and the limitations of this evidence with regard to the populations included, durations studied, and the potentials for important differences in adverse effect profiles between the drugs should be taken into account.

COMMENTARY: In a prior UPDATES article we discussed comparisons of pregabalin with duloxetine (Cymbalta®) and milnacipran (Savella®) — both of which are selective serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants and FDA-approved for treating FMS. All 3 drugs were found to have short-term (up to 6 months) efficacy; although they differed in their adverse effect profiles, with pregabalin appearing to be most advantageous except in patients with depressed mood. There were some limitations of the trials and none compared all 3 drugs head-to-head.
In the present review by Siler and colleagues, the internal validity of the included RCTs was judged as being rather low. This was due to unclear methods of blinding, allocation concealment, and randomization. While the gabapentin trial was government funded, the pregabalin RCTs were supported by the pharmaceutical manufacturer. All of these factors can engender significant bias in research studies, as discussed in our recent UPDATES article on “Making Sense of Pain Research: Part 3.” Both pregabalin and gabapentin were better than placebo in reducing pain in the short-term; however, in absolute terms the magnitude of beneficial effects were limited, with half of patients (at most) experiencing a 30% decrease in pain (while up to one-third had a similar response with placebo). The authors note that the Numbers-Needed-to-Treat, or NNTs, for both drugs were not impressive; specifically, for every 5 patients treated with gabapentin or 8 patients treated with pregabalin (rather than placebo) for 8 to 14 weeks, 1 additional patient would have a response of at least a 30% improvement in symptoms. According to Siler et al., NNTs of 2 to 4 are considered favorable for drug therapies [although their reference source for this assumption is unclear].
Of pregabalin responders, beneficial effects dissipated over time and only about one-third continued to have response at 6 months. While this rate of continued response was better than for those who were switched to placebo, it is still disappointing, the authors believe, considering the long-term duration of FMS symptoms in most patients.
The authors further note that, from an evidence-based medicine perspective, the major components in assessing strength of evidence are: 1) precision of estimates, 2) directness and consistency of evidence, 3) risk of bias, and 4) magnitude of effect. They believe that the overall body of evidence in their review would merit only a low strength of evidence ranking. Furthermore, the clinical applicability (external validity) of the studies was limited by the short duration of all clinical trials and the selective patient population.
A benchmark for therapeutic success in studies to date of antidepressant and antiepileptic agents for FMS appears to be a 30% improvement in symptoms. We have previously described in an UPDATE [here] that 30% to 36% improvements in pain are generally considered by patients as being moderate, with 50% or greater improvements deemed more desirable. This helps to explain why multidrug therapies that combine to increase improvement are commonplace in patients with FMS.
Indeed, Siler and colleagues recommend that better, longer-term comparative trials are needed, which adopt a more “pragmatic” design. That is, including large numbers of patients, with a wide variety of baseline symptoms and comorbidity, and taking multiple medications. However, such “real world” trials can be extremely difficult to construct, conduct, and interpret. And, as we have noted before, pharmacotherapy is only one piece of the puzzle when it comes to successful management of FMS, which often benefits more from multimodal approaches as part of a comprehensive pain management program.
http://updates.pain-topics.org/2011/04/antiepileptic-drugs-for-fibromyalgia.html

What is Lyrica and why is it buying me a new building?

Jan. 16, 2008 By Lara Kattan

The price of the ultimate Northwestern honor – getting a building named after you – has never been released by the university, but the construction of the Silverman Hall for Molecular Therapeutics & Diagnostics might give the ambitious student a clue. It’s named for Richard B. Silverman, a Northwestern chemistry professor, and is being funded by royalty fees collected from his invention of the main chemical compound in Lyrica, an anti-epileptic drug manufactured by Pfizer, Inc.
Although the $700 million Northwestern netted from selling part of their royalty rights to the drug has been widely reported, the impressive workings of Lyrica itself have been left for the chemistry nerds to gawk at. It may have taken a PhD to develop the drug, but it can be explained in terms even the men’s basketball team can understand.
The nerves in the brain send signals to communicate with each other. Sometimes damaged nerves send out more electrical signals than they need to. In people with diabetes, this abnormal firing causes severe stabbing, burning, or shooting pain. When clusters of these nerve cells – called neurons – also fire randomly and repeatedly, it leads to a condition called epilepsy, which is a brain disorder that causes its victims to have occasional to regular seizures.
Silverman joined Northwestern in 1976 and since then, his research has dealt with the mechanisms of epilepsy and neurodegenerative disorders. His group works on understanding the mechanisms of how drugs work, especially ones that deal with inhibiting enzymes. In 1989, they created an organic molecule that binds to nervous system tissues, those same nerves that sometimes over-fire.
In testing the molecule on mice, they found that this “pregabalin” (the scientific name for Lyrica) molecule had an ability to suppress seizures. After testing it and refining it, it was finally approved by the FDA in 2004 and sold by Pfizer, Inc. Its labeled use is for the treatment of partial seizures, fibromyalgia (a chronic pain condition), and nerve pain in those with diabetes.
Silverman now receives royalties from the sale of the drug, as does Northwestern, because he did his research here. Silverman has even donated part of his own royalties to Northwestern, which will be put towards the building named in his honor. Once it’s completed in 2009, Silverman will be moving into the new labs, although he’ll get a smaller office than the one he currently occupies.
“They aren’t planning to knock down any walls for me, but that’s fine,” he said. “I’m just pleased I’ve had the opportunity to give back to the university.”
http://www.northbynorthwestern.com/2008/01/6137/what-is-lyrica-and-why-is-it-buying-me-a-new-building/

U.S. Fibromyalgia Patients Currently Taking an Approved Therapy are More Likely to Request a Discontinuation of Their Treatment in the Next Year Compared with Patients Taking a Non-Approved Therapy.

Eli Lilly and Co

 3/30/2011

EXTON, Penn., Mar 30, 2011 (BUSINESS WIRE) --

Data from a recent report from BioTrends Research Group suggest that U.S. fibromyalgia patients who are currently taking one of the three agents approved for the treatment of fibromyalgia -- Eli Lilly's Cymbalta, Pfizer's Lyrica, and Forest Laboratories/Cypress Biosciences' Savella -- may have higher expectations for their treatment than patients taking off-label therapies. Approximately 40% of surveyed patients taking an approved therapy indicate they are "very unlikely" to ask their doctor to switch their therapy in the next year, compared with more than half of surveyed patients taking an off-label treatment.

"These data suggest that patients currently taking an approved therapy are not well-established on their current treatments, creating a higher risk of drug switching in these patients" said CNS analyst Andrea Buurma. "This indicates there is a significant opportunity for emerging novel agents."

Surveyed patients express they are most likely to request a switch to an agent that offers improvement over their current therapy in treating pain, fatigue, and/or sleep problems. "More than two-thirds of patients indicated they would be somewhat or very likely to switch to an emerging agent that offers improvement in these areas" Ms. Buurma said.

PatientTrends(TM): Fibromyalgia is a yearly report that investigates patients' attitudes, perceptions and behavior regarding their disease, with a focus on the patient's path to diagnosis and their perception of their interaction with their physician. The report looks at what drives patients' satisfaction with their current fibromyalgia treatment and identifies which drug attributes are most likely to prompt a patient to request a switch to an emerging treatment. This report is based on a survey fielded in January and February of 2011 with 500 U.S. patients diagnosed with fibromyalgia.

http://www.stockhouse.com/News/USReleasesDetail.aspx?n=8110160

British Columbia Centre for for study of fibromyalgia and "chronic" Lyme disease

Health officials in British Columbia announced $2 million for a study and new centre that will focus on screening, diagnoses and treatment of patients with fibromyalgia, Lyme disease and chronic fatigue syndrome.

The goal of the study and a new clinic initiated by the Ministry of Health and Provincial Health Services Authority is to accurately diagnose the complicated conditions, and provide treatment and ongoing symptom management to patients.

Ryan Jabs, spokesman for the Health Ministry, said the plan has been in the works for quite some time but was announced now to address recent public concern that the province lacked proper health infrastructure to diagnose and treat patients with chronic illness.

B.C. doctors have been accused of drastically under-diagnosing Lyme disease, in particular, and failing to report the cases that are diagnosed, as required.

In the past many Canadian patients sought treatment for these conditions in the United States, but Jabs said the new centre will educate local doctors on what to look for.

Jabs said it will be a hub for provincial family doctors and will provide an educational component so medical practitioners can accurately recognize and diagnose the chronic conditions.

“There’s considerable debate around the medical community, internationally and locally, on diagnosis and treatment of these types of complex illnesses because there are a lot of symptoms that overlap,” he said.

“They’re rarer conditions and there’s not a centre of expertise. The clinic will help that.”

He said exact details regarding the scope of the study and clinic are in the works, but aren’t expected until the summer. Officials hope to have the study up and running up the fall.

Health Minister Mike de Jong said the additional funds mean B.C. will take a leading role in this area of research.

“I hope that B.C. can help to positively impact patients across the country by studying these illnesses and learning ways to help patients manage their symptoms,” he said in a news release announcing the funding.

Currently, the cause of these debilitating illnesses is unknown, though doctors suspect an infectious agent may play a key role in a patient’s development of chronic diseases.

Recent genome science breakthroughs in DNA sequencing and computer analysis have doctors hoping they’ll have some answers to these complex health issues soon.

About 343,000 Canadians are afflicted with fibromyalgia, a condition that results in chronic pain and stiffness in the muscles and joints, poor sleep and fatigue. Women are approximately 17 per cent more likely than men to develop the illness, according to the federal public health website.

Others with acute Lyme disease were able to be treated with antibiotics to prevent the development of chronic Lyme disease, but in some cases the medication does not prevent the onslaught of the chronic condition.

http://www.theglobeandmail.com/news/national/british-columbia/bc-funds-study-of-fibromyalgia-lyme-disease-chronic-fatigue/article1964319/

Reader's comment:

The BC government was under the gun which is why they coughed up the funds. Last year they secretly commissioned a report on how they are managing Lyme disease in BC. Instead of releasing the findings of the report they tried to bury it.
The report, authored by a very senior person in Provincial Health Services Authority, found that contrary to government messaging that blood tests for Lyme disease were poor, doctors were ignorant, there was no treatment for chronic Lyme disease patients, diagnostic methods were inadequate and the true incidence of Lyme disease in BC was unknown.
The BC government sat on the report and recommendations until the report was obtained through a Freedom of Information request and given to the Vancouver Sun. The Sun came out with a very hard hitting story yesterday and now the BC government is trying to show they are on top of the issue.
Lyme disease is a very serious tick-borne infection. Ticks carrying Lyme disease are found throughout southern Canada and throughout most of British Columbia. In the United States over 35,000 cases of Lyme disease are reported annually - mainly in states adjacent to the Canadian border. In Canada we supposedly have just 30, yes, 30, cases of Lyme disease a year. Obviously something is wrong with this picture.

EU regulator rejects Xyrem as fibromyalgia treatment

 22 Mar 2011

The European Medicines Agency (EMA) has decided not to approve sodium oxybate (brand name Xyrem) as a treatment for fibromyalgia.

Xyrem is an oral solution that is currently used to treat some cases of the sleep disorder narcolepsy in adults.
However, the EMA's Committee for Medicinal Products for Human Use (CHMP) has made the decision not to recommend it for patients with fibromyalgia, a chronic condition that can cause widespread muscle pain. The drug is classed as a controlled substance in the US because of its potential for abuse.
It is thought that as many as one in every 50 people may suffer from fibromyalgia, but there is currently no approved medication for the long-term condition in Europe.
Professor Iris Loew-Friedrich, chief medical officer at pharmaceutical firm UCB, commented: "Upon discussions and following oral explanation with the CHMP, we have to accept that Xyrem in fibromyalgia syndrome will not be recommended for approval in the EU near-term.
"We are very disappointed with the CHMP decision given the significant unmet medical need in fibromyalgia syndrome in Europe today and the consistently positive phase-III clinical trials with Xyrem in the indication."
The decision comes after results from a second phase-III clinical trial of Xyrem in patients with fibromyalgia were presented at the annual meeting of the American Academy of Pain Medicine.
Results from the trial, which involved 376 patients at more than 100 centres in the US and Europe, showed that 51.4 per cent of patients who took 6g per night and 42 per cent of patients who took 4.5g per night benefited from at least a 30 per cent reduction in pain.
In contrast, just 26.8 per cent of patients who took a placebo (dummy treatment) experienced similar levels of pain relief.

A spokesman for Arthritis Research UK commented that there were few effective drugs available to treat fibromyalgia but added that regulators had to be sure that any new drugs were both effective and appropriate.

http://www.arthritisresearchuk.org/about_us/arthritis_news/articles/eu_regulator_rejects_xyrem_as.aspx

United States Court of Appeals

 Argued and Submitted March 9, 2011 — Seattle, Washington.

Cynthia Coleman seeks disability insurance benefits from the Commissioner of Social Security ("Commissioner"). The administrative law judge ("ALJ") determined that Coleman has the residual functional capacity to perform sedentary or light work, so long as she can switch between sitting, standing, and walking at least briefly every hour. Based on testimony provided by a vocational expert ("VE") that Coleman could perform three specified occupations, the ALJ then held that Coleman could perform work that exists in significant numbers in the economy. He therefore denied benefits.

Coleman filed suit in district court, contending that the ALJ erred in two ways. First, Coleman faulted the ALJ for disbelieving her testimony of severe pain on the grounds that her fibromyalgia did not result in certain physical symptoms and that Coleman failed to lose weight as treatment for her obesity.

1. The ALJ relied on the absence of objective physical symptoms of severe pain as a basis for disbelieving Coleman's testimony regarding her symptoms. He erred insofar as Coleman's pain is related to her fibromyalgia, which is a "disease that eludes [objective] measurement."  He also erred by holding, in the middle of a discussion of Coleman's obesity, that her "failure to lose weight reflects on her credibility."

Although we find these errors troubling, we conclude that they were harmless. "[T]here remains substantial evidence supporting the ALJ's conclusions on credibility,"  including Coleman's failure to follow repeated medical recommendations that she treat her pain with exercise and increased activity levels. The ALJ's errors therefore "do not negate the validity of [his] ultimate credibility conclusion" or his resulting determination of Coleman's residual functional capacity.

http://www.leagle.com/xmlResult.aspx?xmldoc=In%20FCO%2020110324179.xml&docbase=CSLWAR3-2007-CURR

High risk of compulsive disorders linked to dopamine-mimic drugs, Mayo confirms

ProHealth.com
March 24, 2011

Typically prescribed for Parkinson’s, restless legs syndrome, fibromyalgia, depression

A Mayo Clinic study has verified earlier findings that harmful compulsive / impulsive behaviors such as binge eating, spending, computer use, and gambling affect one in four people taking a “medium dose” of a dopamine agonist drug such as pramipexole/Mirapex or ropinirole/Requip.

These drugs act like or mimic the chemical messenger dopamine – “stimulating the reward pathways in the brain.” They are FDA-approved for treatment of Parkinson’s disease symptoms (associated with the death of the nerve cells in the brain that make dopamine) and restless legs syndrome. They are also often prescribed off label for fibromyalgia and depression.

Risk of harmful behaviors increases with higher doses - up to one in three, according to Mayo, so patients and their families should be made aware in order to catch behavioral problems early before they cause harm. Reducing or stopping the medication usually resolves the problems, the researchers have found. But this can also involve sometimes severe withdrawal symptoms.
http://www.prohealth.com/library/showarticle.cfm?libid=16039

Pill-free-pain-relief

Chronic pain sufferers may eventually be able to put away the ibuprofen. Just like the song, a new University of Florida study suggests some “good vibrations” take away the pain. UF researchers produced pain by applying heat to the arms of study participants. They followed that pain with stimulating vibrations to block the heat related pain sensations. Researchers say the vibrations reduced the pain sensations in people by 44%. Experts consider this potential new treatment for pain similar to traditional touch therapies already in use.
Dr. Roland Staud/UF pain researcher: “Some forms of massage are very strongly touch related and not painful and they may provide analgesic relief to individuals in pain.”
The study marks the first time a non-painful stimulus was shown to actually provide a pain relieving effect for fibromyalgia patients. Researchers say those who suffer from conditions like fibromyalgia could some day benefit from this kind of treatment, and it could provide an alternative for those who seek treatment from chronic pain.
Dr. Roland Staud/UF pain researcher: “It is not associated with great cost and great risk to the individual as well as the person who provides these treatments.”
Experts say more than 75 million people suffer from chronic pain the United States.
http://news.ufl.edu/2011/03/23/pill-free-pain-relief/

European Medicines Agency decided against Xyrem (sodium oxybate)

Adrienne Dellwo, March 21, 2011
The European Medicines Agency has decided against recommending Xyrem (sodium oxybate) for treating fibromyalgia in adults. To date, the European Union doesn't have any medications approved for fibromyalgia.
Xyrem is approved in both the EU and the U.S. for narcolepsy and cataplexy (a narcolepsy symptom.) The U.S. FDA rejected this medication as a fibromyalgia treatment in October 2010, citing concerns over safety because it's similar to the date-rape drug GHB.
In clinical trials, Xyrem has been shown to improve the quality of stage-four sleep in fibromyalgia. Disrupted deep sleep is believed to be a primary contributor to symptoms of this illness and may play a role in its pathogenesis.
http://chronicfatigue.about.com/b/2011/03/21/eu-says-no-to-proposed-fibromyalgia-drug.htm

Sodium oxybate reduces pain, fatigue, and sleep disturbance and improves functionality in fibromyalgia: results from a 14-week, randomized, double-blind, placebo-controlled study

14 March 2011.
This 14-week, phase 3, double-blind, randomized, controlled trial evaluated sodium oxybate (SXB) 4.5 and 6g per night versus placebo in patients with fibromyalgia (FM). SXB is the sodium salt of γ-hydroxybutyrate (GHB). GHB is an endogenous compound, synthesized from γ-aminobutyric acid (GABA) and found broadly in the central nervous system and body. Among 548 randomized patients, a 30% reduction in pain was experienced by 54.2% and 58.5% of patients treated with SXB 4.5 and 6g, respectively, versus 35.2% for placebo with a 100-mm Visual Analog Scale (VAS) (P<0.001 for both comparisons). Relative to placebo, both SXB doses significantly reduced fatigue (with a 100-mm VAS; P<0.001) and sleep disturbance (with the Jenkins Sleep Scale; P<0.001), and resulted in significant improvements in function as measured by the FM Impact Questionnaire (P=0.003 and P=0.001 for 4.5 and 6g per night, respectively). On the Short-Form 36 Health Survey, SXB-related improvement was significant on the Physical, but not the Mental, Component Scale. The proportion of patients who reported a global improvement of “much” or “very much” better on the Patient Global Impression of Change was significantly greater in both SXB groups versus placebo (P<0.001). Headache, nausea, dizziness, vomiting, diarrhea, anxiety, and sinusitis were the most commonly reported adverse events, with an incidence at least twice that of placebo. These results expand the evidence from previous clinical trials suggesting that SXB is effective and safe in FM.

 http://www.painjournalonline.com/article/PIIS0304395910007724/abstract?rss=yes

Pico-Tesla receives ISO certification for "Magneceutical Therapy"

Pico-Tesla, The Magneceutical^® Company, has received the International Organization for Standardization (ISO) 13485:2003 certificate for the "design, development, production, manufacture and distribution of resonator systems that generate a low-level electromagnetic field for the therapeutic treatment of disease."
ISO 13485:2003 specifies requirements for a Quality Management System whereby a company must demonstrate its ability to provide medical devices and related services that consistently meet the highest quality standards related to the clinical needs of patients and healthcare providers. The certification satisfies Health Canada as a pre-requisite for medical device distribution into Canada, and is also aligned to meet the requirements to the European Medical Device Directive (MDD) 93/42/EEC as amended by 2007/47/EC, to place the CE mark on its products. The certification is a significant step in Pico-Tesla demonstrating conformance to medical device safety and effectiveness requirements, thus strengthening the Company's ability to enter worldwide markets.
"Receiving the ISO 13485 certification bears strong witness to the significant progress we are making toward establishing the clinical application of Magneceutical® Therapy for Parkinson's and other difficult-to-treat diseases," said Allen Braswell, CEO of Pico-Tesla.
"There is one thing that has stayed in my mind since getting involved with this opportunity. That is, to be so driven and committed to quality in such early stages of your product development is not a typical behavior of many companies, whether they are big or small. That commitment driven from the top can only bring continued success!" said Lynette Makowski, Principal Consultant, Achieving RA/QA Compliance LLC, a Regulatory and Quality Expert in the Medical Device Industry.
Pico-Tesla's Magneceutical^® Therapy is currently in clinical trials to determine its effectiveness for improving the signs and symptoms of several diseases, including  fibromyalgia.
 http://www.news-medical.net/news/20110315/Pico-Tesla-receives-ISO-certification-for-Resonator-device.aspx

Eli Lilly and Cymbalta

Eli Lilly appears perilously perched on the precipice of a patent cliff. A plummet could result in revenue falling for at least the next two years, and loss of more than 75% of sales within the next 7 years. Worse yet, there’s no parachute of freshly approved drugs to replace this revenue. Lilly’s perch is perhaps the best example of the crisis faced by much of the pharmaceutical industry faces. However, it’s not the end of the world. Even acrophobic investors should take a closer look at patent expiration dates before abandoning hope of possible replacements for this revenue.
Unlike an Abbott or Johnson & Johnson, Eli Lilly is nearly a pure pharmaceutical company, without a significant medical devices or consumer business segment. Eli Lilly has a focus on neuroscience (40.8% of 2010 revenue), endocrinology (26.6%), oncology (16.2%), and cardiovascular drugs (9.4%). Other pharmaceutical segments are 0.9% of revenues, and animal health makes up the remaining 6.0% of revenues. Lilly’s bestselling drug is the schizophrenia treatment Zyprexa, which begins the flood of U.S. patent losses later this year. The next highest seller at $3.5 billion and 15% of revenues is Cymbalta, used to treat depression and fibromyalgia, and is on patent until at least June 2013. http://seekingalpha.com/article/258092-how-eli-lilly-will-face-patent-expirations

European Medicines Agency recommend against Xyrem for fibromyalgia

UCB (UCBJF) recently reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended against the approval of Xyrem for the treatment of fibromyalgia syndrome in adults.
We note that Xyrem is already marketed in the European Union (EU) for the treatment of narcolepsy with cataplexy in adults. UCB markets the drug in the EU under a license from Jazz Pharmaceuticals Inc. http://www.zacks.com/stock/news/49378/UCB+Faces+Setback

Sodium oxybate -- a GABA derivative

Abstract 

This 14-week, phase 3, double-blind, randomized, controlled trial evaluated sodium oxybate (SXB) 4.5 and 6g per night versus placebo in patients with fibromyalgia (FM). SXB is the sodium salt of γ-hydroxybutyrate (GHB). GHB is an endogenous compound, synthesized from γ-aminobutyric acid (GABA) and found broadly in the central nervous system and body. Among 548 randomized patients, a 30% reduction in pain was experienced by 54.2% and 58.5% of patients treated with SXB 4.5 and 6g, respectively, versus 35.2% for placebo with a 100-mm Visual Analog Scale (VAS) (P<0.001 for both comparisons). Relative to placebo, both SXB doses significantly reduced fatigue (with a 100-mm VAS; P<0.001) and sleep disturbance (with the Jenkins Sleep Scale; P<0.001), and resulted in significant improvements in function as measured by the FM Impact Questionnaire (P=0.003 and P=0.001 for 4.5 and 6g per night, respectively). On the Short-Form 36 Health Survey, SXB-related improvement was significant on the Physical, but not the Mental, Component Scale. The proportion of patients who reported a global improvement of “much” or “very much” better on the Patient Global Impression of Change was significantly greater in both SXB groups versus placebo (P<0.001). Headache, nausea, dizziness, vomiting, diarrhea, anxiety, and sinusitis were the most commonly reported adverse events, with an incidence at least twice that of placebo. These results expand the evidence from previous clinical trials suggesting that SXB is effective and safe in FM.

 http://www.painjournalonline.com/article/PIIS0304395910007724/abstract?rss=yes

Dangers of Paracetamol, Acetaminophen

Blogger's Note:
I thought long and hard about including this in the blog, but decided the dangers of Paracetamol (Acetaminophen, Tylenol), even in therapeutic dosage, are not as well known as they should be.


Paul Cassell
March 08, 2011

A psychiatrist admitted medics at Prospect Park Hospital gave too much medication to a suicidal woman who was later found dead after taking an overdose.
Dr Giovanni Borghini made the frank confession at an inquest into the death of Bridget Proctor at Reading Civic Centre last Tuesday, to the amazement of Mrs Proctor’s daughters Suzanne and Beverley.
The 59-year-old was found dead by a care team from the Tilehurst hospital with several packets of medication by her side in the bedroom of her home in Shilling Close, Tilehurst, on Thursday, April 1, last year.
The inquest heard she had been given two weeks’ worth of medication, predominantly paracetamol, from staff at Prospect Park instead of three days. A failure in communication meant she was given her full allocation.
Giving evidence, Dr Borghini said: “I must say in this case the initial plan was to give her no more than three days of medication and hand over the rest of the supply to the home treatment team.
“The reason why that hasn’t happened is because of a mistake for which I take full responsibility.”
Dr Borghini admitted it was the only mistake he had made in his career and what had happened had reflected on him, the staff and the hospital. He added that lessons had been learned to ensure this could never happen again.
The inquest heard Mrs Proctor had suffered with fibromyalgia, a muscle pain common with psychiatric conditions such as depression and anxiety and stress-related disorders such as post-traumatic stress disorder. Dr Borghini explained there was no known cure for the condition and it was generally treated with painkillers.
He confirmed that Mrs Proctor had suffered with depression for many years and was on a range of medication.
In 2000 Mrs Proctor took a large overdose of prescribed medication and spent time at Prospect Park. After a period of review doctors had no major concerns and she was discharged.
Last March she told her family she was “considering ending it all” and was readmitted to the hospital, where she remained for two weeks during which time she underwent treatment and observation.
Doctors agreed she could be discharged early and provided her with two weeks’ worth of medication, having intended to give her enough for three days and arrange for the rest to be administered on a daily basis by the home care team.
A toxicology report revealed Mrs Proctor had a high level of paracetamol, along with antidepressant codine and lamotrigine, an antiepileptic drug used to treat bipolar disorder.
Blood tests further revealed the paracetamol had most likely caused liver failure.
Recording a narrative verdict, the coroner Peter Bedford said Mrs Proctor died from aspiration pneumonia caused by a combination of toxicity from the deliberate digestion of codine, lamotrigine and paracetamol against a background of depression.
He added she had been mistakenly given two weeks medication even though she remained a potential risk of taking an overdose and “an opportunity had been presented to her” to take her own life.
paulcassell@trinitysouth.co.uk
http://www.getreading.co.uk/news/s/2088945_doctor_i_gave_wrong_dosage

Jazz Pharmaceuticals Inc. Reports Operating Results (10-K)

We have a number of product candidates in various stages of clinical development. In 2010, 2009 and 2008 we spent $25.6 million, $36.6 million and $70.0 million, respectively, on research and development activities.

UCB has the right to market JZP-6 for the treatment of fibromyalgia in 54 countries outside the United States. UCB has submitted an application to the European Medicines Agency for approval to market and promote JZP-6, and if it is approved, we are entitled to a milestone payment of up to $25 million, royalties on UCB’s sales of JZP-6 and additional commercial milestone payments of up to $100 million. No product has been approved in Europe for the treatment of fibromyalgia. The term of our agreement with UCB, as it applies to JZP-6, extends to the later of the expiration of our associated patent rights in the territories covered by the agreement or ten years from the date of EMA approval to commercially promote and distribute the product for the treatment of fibromyalgia, subject to automatic extension unless UCB provides 12 months’ notice. UCB may terminate our agreement for any reason upon 12 months’ notice and may terminate its rights to JZP-6 for the treatment of fibromyalgia on six months’ notice at any time prior to the receipt of marketing approval of JZP-6 for fibromyalgia in the European Union. We are responsible for supplying JZP-6 to UCB in exchange for supply price payments.

http://www.gurufocus.com/news.php?id=125144

Pfizer Touts New Drug for Fibromyalgia (Lyrica), Critics Warn Consumers

By Shaun Hittle
Pfizer’s new television commercial for the medication Lyrica, features a middle-aged woman who says that her Fibromyalgia (FMS) is real and that she can now live without pain thanks to the medication.
The advertisement for the first FDA approved medication for Fibromyalgia is aimed at making two arguments: that Fibromyalgia is a real condition, and that Lyrica can lessen its symptoms.
Some critics, however, still argue that Fibromyalgia is not a real medical condition and that consumers need to be skeptical of claims made by pharmaceutical companies.
As defined by the National Fibromyalgia Research Association, Fibromyalgia is a pain disorder characterized by sleep problems and pain and stiffness in numerous sites of the body. Estimates regarding the prevalence of this illness vary, but advocacy groups put the total number of sufferers for FMS at roughly six million in the US.
While the condition is accepted by insurance companies and well-known medical organizations, controversy regarding the existence of the disease still exists. In a recent NY times article, Dr. Frederick Wolfe, who authored the 1990 paper that was the first to establish parameters for FMS, was quoted as refuting his earlier claims that FMS was a real illness. “Some of us in those days thought we had actually defined a disease, which this is clearly not,” said Wolfe in the article.
However, as sales for the drug soar, the public and many in the medical community seem to be buying both of Pfizer’s arguments. Fourth quarter sales as reported by Pfizer for Lyrica, which was approved for the treatment of FMS in the summer of 2007, totaled $564 million; a 60 percent increase from the previous quarter, and annual sales of Lyrica totaled $1.8 billion in 2007 (Lyrica is also used for other medical conditions but Pfizer does not detail sales in terms of reason for prescribing).

Trial Results
In clinical trials for Lyrica, patients experienced a decrease in pain by an average of two points on a ten point scale, compared to an average of one point for placebo, and 30 percent of patients reported a pain decrease by half, compared to 15 percent taking placebo.
Despite these results and FDA approval of Lyrica, patient and consumer advocates argue that consumers need to be cautious about claims made by the local pharmaceutical giant.
Dr. Larry Sasich, a pharmacologist at the Lake Erie College of Osteopathic Medicine (LECOM) and former employee of the consumer watchdog, Public Citizen, warns the public that the information they get in 30 second TV commercials is not the entire story when it comes to a drug, its side effects, or its effectiveness.
“People need to have more information,” said Sasich, noting that physicians should be spending more time reviewing the complicated clinical trials and determining their effectiveness. This, according to Sasich, will provide a buffer between the pharmaceutical industry’s claims and more concrete scientific data and research.
But the bottom line for those suffering from FMS, is that the drug’s approval means some hope for alleviating the symptoms.
Sharon Waldrop, President of the Fibromyalgia Association of Michigan, says that her organization welcomes the new drug and hopes other medications might also soon be approved for the illness. “Finally there is a medication that is specifically shown to help treat pain and disturbed sleep patterns patients experience with fibromyalgia,” said Waldrop.
Pfizer’s advertising track record
For those embracing Pfizer’s claims that Lyrica can treat fibromyalgia, a closer look at Pfizer’s track record regarding their advertising of medications may cause consumers to proceed with caution when deciding whether or not to start taking Lyrica.
Consumer’s International, an international consumer watchdog, has compiled a long list on their website detailing Pfizer’s past history of claims by consumers and industry professionals about false and inaccurate advertising. Included in this list is Pfizer’s guilty plea for falsely marketing the epilepsy drug, Neurontin, for off label uses and Pfizer’s claims about Zoloft’s ability to reduce the likelihood that patients would harm themselves, though actual studies showed the opposite.
Lynne Matallana, President of the National Fibromyalgia Association and a sufferer of FMS, says that she does not have concerns about Pfizer’s advertising or the process by which Lyrica was tested. “It a very rigorous process,” said Matallana regarding the required FDA trials.
For those suffering from FMS and for Pfizer, Dr. Sasich’s recommendation for consumers wanting to try new medications might be difficult to follow: avoid using any new drug until it’s been on the market for at least seven years.
Pfizer Spokes-person Stephen Borboroglu, however, con- tends that Lyrica has already been used by seven million patients worldwide since its first approval by the European Union in 2004. “Numerous credentialed experts in the filed have presented data on Lyrica’s efficacy and safety in several peer-reviewed forums…” said Borboroglu, further explain- ing Pfizer’s stance that Lyrica is a safe and effective medication.
Sasich’s statement also gets a strong reaction from Matanalla: “That’s insane…The large majority of people are not going to wait seven years,” Matanalla said
http://www.kalamazooweekly.com/archive.php?id=103

Improvement in Fibromyalgia Pain Scale Quantified

A two-point improvement on the Brief Pain Inventory represents the minimum clinically important difference for patients with fibromyalgia pain, corresponding to a 30 to 35 percent improvement from baseline, according to a study published online Feb. 10 in Arthritis Care & Research.


TUESDAY, March 8 (HealthDay News) -- A two-point improvement on the Brief Pain Inventory (BPI) represents the minimum clinically important difference (MCID) for patients with fibromyalgia pain, corresponding to a 30 to 35 percent improvement from baseline, according to a study published online Feb. 10 in Arthritis Care & Research.
Philip J. Mease, M.D., of the University of Washington School of Medicine in Seattle, and colleagues used data from four studies evaluating duloxetine as a treatment for fibromyalgia. They estimated the MCID for the BPI average pain item score and the BPI severity score by anchoring them against the Patient Global Impression of Improvement scale.
The researchers determined that an approximately two-point improvement on both the BPI average pain item and severity scores represented the MCID. These MCIDs corresponded to a 30 to 35 percent improvement in baseline pain in both scores.
"These findings may be beneficial for use in designing clinical trials in which the BPI is used to evaluate improvements in pain severity," the authors write.
The study received financial support from Eli Lilly and Company and Boehringer Ingelheim GmbH

Jazz Pharmaceuticals; JZP-6, JZP-7

Jazz Pharmaceuticals, Inc., a specialty pharmaceutical company, develops and commercializes products for neurology and psychiatry primarily in the United States.
 The company’s late-stage product candidate comprises JZP-6, which has completed two Phase III pivotal clinical trials, for the treatment of fibromyalgia.
 JZP-7, a transdermal gel formulation of ropinirole for the treatment of restless legs syndrome.
In addition, the company is developing oral tablet forms for sodium oxybate. Jazz Pharmaceuticals, Inc. was founded in 2003 and is headquartered in Palo Alto, California.
 http://stockreads.com/Stock-Newsletter.aspx?id=42159#ixzz1Fph8Gzis

Droxidopa, Northera, and Chelsea Therapeutics

CHARLOTTE, N.C. (AP) - Chelsea Therapeutics International Ltd. reported a wider fourth-quarter loss Wednesday as it continued development of its hypotension drug candidate Northera.
Chelsea Therapeutics does not have any products on the market, and it did not report any revenue. The company is preparing to file for Food and Drug Administration approval of Northera, and hopes to launch the drug in early 2012.
Northera is designed to treat neurogenic orthostatic hypotension, which is a drop in blood pressure on standing. The FDA plans to conduct an expedited six-month review of the company's marketing application, and if the drug is approved, it will receive extended market exclusivity.
Chelsea Therapeutics said its research and development costs climbed to $10.2 million from $4 million. It said development of Northera, along with initial manufacturing and validation of the active ingredient in the drug, and a mid-stage trial of a rheumatoid arthritis drug were the causes of the increase in spending.
The active ingredient in Northera is droxidopa. Chelsea Therapeutics is also studying droxidopa as a treatment for fibromyalgia, a chronic disease that causes muscle pain and fatigue.
http://www.canadianbusiness.com/markets/market_news/article.jsp?content=D9LNCBS80

ACUPUNCTURE: Effects of acupuncture on patients with fibromyalgia: study protocol of a multicentre randomized controlled trial

Fibromyalgia is a multidimensional disorder for which treatment as yet remains unsatisfactory. Studies of an acupuncture-based approach, despite its broad acceptance among patients and healthcare staff, have not produced sufficient evidence of its effectiveness in treating this syndrome.

The present study aims to evaluate the effectiveness of individualized acupuncture for patients with fibromyalgia, with respect to reducing their pain and level of incapacity, and improving their quality of life.Methods/designRandomized controlled multicentre study, with 156 outpatients, aged over 17 years, diagnosed with fibromyalgia according to American College of Rheumatology criteria, either alone or associated with severe depression, according to the criteria of the Diagnostic and Statistical Manual for Mental Disorders. The participants will be randomly assigned to receive either "True acupuncture"or "Sham acupuncture".

They will be evaluated using a specific measurement system, constituted of the Fibromyalgia Impact Questionnaire and the Hamilton rating scale for depression. Also taken into consideration will be the clinical and subjective pain intensity, the patient's family structure and relationships, psychological aspects, quality of life, the duration of previous temporary disability, the consumption of antidepressant, analgesic and anti-inflammatory medication, and the potential effect of factors considered to be predictors of a poor prognosis.

All these aspects will be examined by questionnaires and other suitably-validated instruments. The results obtained will be analysed at 10 weeks, and 6 and 12 months from the start of treatment.DiscussionThis trial will utilize high quality trial methodologies in accordance with CONSORT guidelines.

It may provide evidence for the effectiveness of acupuncture as a treatment for fibromyalgia either alone or associated with severe depression.Trial registrationISRCTN trial number ISRCTN60217348 (19 October 2010)

Author: Jorge VasManuela ModestoInmaculada AguilarKoldo Santos-ReyNicolas Benitez-ParejoFrancisco Rivas-Ruiz
Credits/Source: Trials 2011, 12:59
http://7thspace.com/headlines/374196/effects_of_acupuncture_on_patients_with_fibromyalgia_study_protocol_of_a_multicentre_randomized_controlled_trial_.html

Tai Chi: A gentle approach to Martial Arts

Angele Cano

ENFIELD: Slow fluid movements, gradual rotations, and gentle gestures. This is what you might see a group of dedicated individuals practicing in Enfield on any given Wednesday night.

For the past two years, Phil Blois has been teaching Taoist Tai Chi (TTC) at the Enfield Legion Hall in Enfield, but his own practice began when he was 25. Now, he, along with more than 40,000 people who practice this form of the gentle martial art, tout the health, social, and rehabilitative benefits of the practice—increased flexibility, balance, agility, relaxation and coordination are a few.
“As I get older, instead of losing mobility, strength, and flexibility, I’ve actually found mine have been improving” said Blois. “These are things things people usually associate with aging, but I tend to surprise students in my class with what I can do, as far as strength and flexibility.”
Taiost Tai Chi society was founded in 1970 by Moy Lin-shin, a monk who immigrated to Canada from Hong Kong. The practice now spans 25 countries across the globe practicing ‘the internal art of taijiquan’, a sequence of 108 movements that flow together, and is said to improve health from the inside, from a holistic perspective.
The movements incorporate balance, weight bearing from lifting limbs, rotating, hopping, reaching, and stretching, and while the practice tends to associated with an older crowd, Blois said it benefits all ages. Blois said the age range of people who practice tends to follow the demographic, so in Nova Scotia, the average age of students is higher, although he’s had members attend his class who are as young as 18.
“The benefits of Tai Chi for someone younger come much quicker because there’s less to overcome,” said Blois. “It’s unfortunate that most of us have to be around 40 before we realize we have to change the way we treat our bodies.”
Dr. Mary Lynch, director of the Pain Management Unit at Capital Health Nova Scotia (CDHA) and Dalhousie professor, said the practice can aid in pain management. She referred to a recent study that followed people suffering with fibromyalgia and began to incorporate Tai Chi and the similar practice of Chi Gong. Participants reported improved sleep, energy levels, and decreased pain.
“I think it’s very promising,” said Lynch, “It’s a self practice technique that patients and people living with pain can learn, and then have it with them for the rest of their lives. It’s also less invasive than any other treatments out there. Every drug has side effects. Every treatment has potential adverse consequences. (Tai Chi) does not appear to have any adverse effects.”
The TTC society’s medical advisor claims the practice provides benefits for those suffering from rheumatoid arthritis, osteoarthritis, Parkinson’s disease, and Multiple Sclerosis.
“It’s easy to get started,” said Blois. “It’s not terribly demanding in the beginning and can learn at your own pace as your strength improves, and your balance and coordination improves.”
And those who work desk jobs take note. According to a recent study completed by York University in Toronto, in the journal, WORK: A Journal of Prevention, Assessment and Rehabilitation, Tai Chi can help to alleviate musculoskeletal disorders from the effects of sitting in front of a computer for extended periods.
The study followed 50 female computer users who followed a twice weekly, four month mid-day Tai Chi program. It found that participants achieved improved spinal and back health, reduced the effects of tendinitis and carpal tunnel syndrome, lower resting heart rate and a reduced waist circumference. They also experienced a psychological boost.
Blois said he began practicing because he was looking for something to maintain his health, along with running and cycling, and was more attracted to this non-competitive martial art.
“I really liked doing it,” he said. “I liked the atmosphere of the club, and my overall health improved. I really appreciate the art and what it’s capable of doing and how people improve their health.”
He said he notices similar effects in the students in his class. He recalled a few former students, one, who was able to stand on her own unassisted to cook a meal on her stovetop. Another student had ankylosing spondylitis, a condition that causes fusing of vertebrae in the spine and he experienced increased mobility and a straighter spine. Still another student who was wheel chair bound was walking within a few months of beginning practice.
But for results like this, Blois said the practice takes major commitment, time, determination and dedication.
“It’s not a cure all for disease,” he said, “but a lot of times symptoms are reduced as the body gets healthier, symptoms of diseases are lessened, some people find that they need to take less medication if they’re practicing Tai Chi.”
Blois is a veteran instructor—he’s been at it for 21 years, and he does it all for free. Another thing about the society, they are a no-for-profit organization and registered charity. Registration fees—also paid by instructors—go towards administrative costs, and extending the reach of the practice to places like Enfield. Instructors are also required to attend workshops, paid for out of pocket, to improve their practice and teaching skills.
“This really is putting your money where your mouth is,” said Blois. “It’s not just face value. It’s showing you believe in what you’re doing. The organization has done a lot for me, health wise social activity wise, I learned a lot about the Chinese culture and people from all different walks of life. That’s something I value.”
It’s advised to consult your family physician before starting any exercise program. For more information, visit www.taoist.org.
acano@enfieldweeklypress.com
http://www.enfieldweeklypress.com/stories.asp?id=5067

MEDA (AB) and Flupirtine

2/14/2011

CEO'S COMMENTS 

As I predicted and communicated last year, fiscal 2010 was somewhat of an off-year for company growth.   I would rather characterize the year past as a very eventful year.
Meda's pipeline has been further strengthened, and several products have made great headway during the year such as flupirtine (treatment of fibromyalgia).
Meda's focus on growth markets, such as Russia, Turkey, Poland, and Mexico, has also shown excellent results in 2010 with an average increase in sales of more than 20 percent
http://www.cisionwire.com/meda/meda-ab--publ----2010-year-end-report85727

FDA decision on Xyrem

Xyrem (sodium oxybate), which was recently denied as a fibromyalgia treatment, is on the list because of the risk of death. Xyrem is approved for narcolepsy symptoms and is a Schedule III federally controlled substance.
http://chronicfatigue.about.com/b/2011/02/14/fda-watch-for-fibromyalgia-chronic-fatigue-syndrome-drugs.htm