Saturday, 23 April 2011

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).

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%.,+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.

Thursday, 14 April 2011

Fibromyalgia and obesity: the hidden link

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.

Monday, 11 April 2011

Balneotherapy in fibromyalgia: A single blind randomized controlled clinical study

Rheumatology International, 04/11/2011  Clinical Article

Ă–zkurt S et al. – It was concluded that balneotherapy provides beneficial effects in patients with fibromyalgia.
  • 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

  • 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

Sunday, 10 April 2011

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.

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.

Tuesday, 5 April 2011

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.”

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
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.

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.

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.