European CHMP Adopts Negative Opinion on Cymbalta for the Treatment of Fibromyalgia
24 October 2008 - 9:00PM
PR Newswire (US)
INDIANAPOLIS, Oct. 24 /PRNewswire-FirstCall/ -- The Committee for
Medicinal Products for Human Use (CHMP) of the European Medicines
Agency (EMEA) has adopted a negative opinion on a Cymbalta(R)
(duloxetine hydrochloride) application for the treatment of
fibromyalgia. "Eli Lilly and Company and Boehringer Ingelheim are
naturally disappointed by the CHMP's opinion," said James Russell,
M.D., global medical director for duloxetine, Eli Lilly and
Company. "We remain confident in the duloxetine data." No
medication has been approved in Europe for the treatment of
fibromyalgia, a disease characterized by chronic widespread pain.
The CHMP received data on the use of duloxetine in the treatment of
fibromyalgia in 1,411 patients in four placebo-controlled studies
and 350 patients in one open-label safety study, a total of 1,761
patients in five clinical trials.(1,2,3,4,5) The cause of
fibromyalgia remains unknown;(6) however, scientists believe it may
be related to some combination of genetic disposition(7) and
subsequent changes in pain processing in the brain.(6) The
disorder, which has a worldwide prevalence ranging from 0.5 percent
to 5.0 percent of the population,(8) has a high impact on quality
of life. In addition to chronic widespread musculoskeletal pain,
many fibromyalgia patients experience other symptoms such as
tenderness, fatigue, sleep disturbance, anxiety and
depression.(1,9) In Europe, duloxetine has been approved for the
treatment of diabetic peripheral neuropathic pain (DPNP), major
depressive episodes, generalised anxiety disorder (GAD) and stress
urinary incontinence (SUI). Duloxetine was approved in the United
States for the management of fibromyalgia in June 2008 by the U.S.
Food and Drug Administration (FDA). Notes to Editors: About
Fibromyalgia Fibromyalgia is difficult to diagnose, partly because
no diagnostic tests for the disease exist(10) and partly because a
number of other conditions (both treatable and life-threatening)
have similar symptoms.(10) To diagnose fibromyalgia, physicians
apply pressure to a series of "tender points" throughout the
body(9) and ask the patient if it feels painful. The American
College of Rheumatology (ACR) classification criteria for
fibromyalgia are the most commonly used in clinical and therapeutic
research.(11) The accepted diagnostic criteria require that
spontaneous pain be present for over three month's duration along
the spine and in all four quadrants of the body.(10) About
Duloxetine While duloxetine's mechanism of action in humans is not
fully known, it is believed to affect both serotonin and
norepinephrine/noradrenaline mediated nerve signaling in the brain
and the spinal cord. Based on pre-clinical studies, duloxetine is a
reuptake inhibitor of serotonin and norepinephrine/noradrenaline.
Scientists believe its effect on pain perception is due to
increasing the activity of serotonin and norepinephrine in the
central nervous system. Duloxetine is approved for the treatment of
major depressive disorder and diabetic peripheral neuropathic pain
in many countries, and is approved in some countries for the
treatment of stress urinary incontinence and generalised anxiety
disorder. Duloxetine is approved only for adults 18 and over. There
is a possibility of an increased risk of suicidal thoughts or
behaviour in children and young adults treated with
antidepressants. Patients should call their doctor right away if
they experience worsening depression symptoms, unusual changes in
behaviour or thoughts of suicide, especially at the beginning of
treatment or after a change in dose. Patients taking duloxetine may
experience dizziness or fainting upon standing. The most common
side effects of duloxetine include: -- For depression: Nausea, dry
mouth, headache, insomnia, diarrhoea -- For diabetic peripheral
neuropathic pain: Nausea, somnolence (sleepiness), fatigue,
headache, dizziness -- For generalised anxiety disorder: Nausea,
fatigue, dry mouth, drowsiness, constipation, insomnia, decreased
appetite, hyperhidrosis (excessive perspiration), decreased libido,
vomiting, ejaculation delay and erectile dysfunction. -- For stress
urinary incontinence: Nausea, dry mouth, fatigue. This is not a
complete list of side effects. 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), fluvoxamine, ciprofloxacin or enoxacine or who have severe
kidney disease. The initiation of treatment with duloxetine also is
contraindicated in patients with uncontrolled hypertension that
could expose patients to a potential risk of hypertensive crisis.
Eli Lilly and Company and Boehringer Ingelheim In November 2002,
Eli Lilly and Company and Boehringer Ingelheim signed a long-term
agreement to jointly develop and commercialize duloxetine
hydrochloride. This partnership covers neuroscience indications in
most countries outside of the United States and Japan, with few
exceptions. About Eli Lilly and Company Lilly, a leading
innovation-driven corporation, is developing a growing portfolio of
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, Ind., Lilly provides answers -- through medicines
and information -- for some of the world's most urgent medical
needs. For more information please visit http://www.lilly.co.uk/.
About Boehringer Ingelheim The Boehringer Ingelheim group is one of
the world's 20 leading pharmaceutical companies. Headquartered in
Ingelheim, Germany, it operates globally with 135 affiliates in 47
countries and almost 38,900 employees. Since it was founded in
1885, the family-owned company has been committed to researching,
developing, manufacturing and marketing novel products of high
therapeutic value for human and veterinary medicine. In 2007,
Boehringer Ingelheim posted net sales of 10.9 billion euro while
spending one fifth of net sales in its largest business segment
Prescription Medicines on research and development. For more
information please visit http://www.boehringer-ingelheim.com/.
Duloxetine for major depressive episodes, diabetic peripheral
neuropathic pain and generalised anxiety disorder is marketed by
Lilly and Boehringer Ingelheim in all countries included in the
partnership under the brand name Cymbalta, except for Germany,
Greece, Italy and Spain. In Germany, Lilly and Boehringer Ingelheim
market duloxetine for major depressive episodes under the brand
name Cymbalta, and market the product for diabetic peripheral
neuropathic pain as Ariclaim(R). In Greece, Italy and Spain Lilly
markets the product as Cymbalta and Boehringer Ingelheim markets
the product as Xeristar(R). In the United States, Cymbalta is
marketed by Lilly and Quintiles. In Japan, duloxetine is
co-developed and co-marketed by Lilly and Shionogi & Co., Ltd.
Duloxetine for stress urinary incontinence is marketed by Lilly
under the brand name Yentreve(R). (1) Russell, IJ, et al. Efficacy
and Safety of Duloxetine for Treatment of Fibromyalgia in Patients
With or Without Major Depressive Disorder: Results From A
Six-Month, Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose
Trial, Pain. 2008. (2) Arnold, L, et al. A Randomized,
Double-Blind, Placebo Controlled Trial of Duloxetine in the
Treatment of Women with Fibromyalgia With or Without Major
Depressive Disorder. Pain. 2005; 119 (1-3): 5-15 (3) Arnold, L, et
al. A Double-Blind, Multicenter Trial Comparing Duloxetine with
Placebo in the Treatment of Fibromyalgia Patients With or Without
Major Depressive Disorder. Arthritis Rheum 2004; 50(9):2974-84. (4)
Chappell, AS, et al. Duloxetine 60-120 mg Versus Placebo in the
Treatment of Fibromyalgia Syndrome. Poster presented at the
American College of Rheumatology Annual Meeting; Nov 2007, Boston,
MA. (5) Chappell, AS, et al. A 1-Year Safety and Efficacy Study of
Duloxetine in Patients with Fibromyalgia. Poster presented at
European League Against Rheumatism Annual Meeting; Jun 2008, Paris,
France. (6) Leventhal, LJ. Management of Fibromyalgia. Annals of
Internal Medicine. 1999; 131: 850-858. (7) Arnold, L, et al. Family
Study of Fibromyalgia. Arthritis & Rheumatism. 2004; 50(3):
944-952. (8) White, et al. Classification, Epidemiology, and
Natural History of Fibromyalgia. Current Pain and Headache Reports
2001; 5:3320-329 (9) Epstein, SA, et al. Psychiatric Disorders in
Patients with Fibromyalgia. Psychosomatics. 1999; 40(1):59 (10)
Rao, SG, et al. Understanding the Fibromyalgia Syndrome.
Psychopharmacology Bulletin. 2007: 4:24-67 (11) Carville, SF, et
al. EULAR Evidence-based Recommendations for the Management of
Fibromyalgia Syndrome. Ann Rheum Dis. Republished 2008: 67:
536-541. P-LLY (Logo:
http://www.newscom.com/cgi-bin/prnh/20070319/NYM004LOGO )
http://www.newscom.com/cgi-bin/prnh/20070319/NYM004LOGO DATASOURCE:
Eli Lilly and Company CONTACT: Charlie McAtee, +1-317-277-1566,
Sonja Popp-Stahly, +1-317-655-2993, both of Eli Lilly and Company;
or John Pugh, Boehringer Ingelheim, + 49 (6132) 77-2964
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