National Horizon Scanning Centre. Ampligen for chronic fatigue syndrome. December 2007

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1 Ampligen for chronic fatigue syndrome December 2007 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The Research Programme is part of the National Institute for Health Research

2 Ampligen for chronic fatigue syndrome Target group Chronic fatigue syndrome (CFS) / myalgic encephalomyelitis (or encephalopathy) (ME). Technology description Ampligen (poly1:polyc12u) is the first in a new class of toll-like receptor 3 agonist. It is administered intravenously twice weekly at 400 mg. The likely treatment duration is oneyear. Ampligen reportedly activates a cellular immune response, mimicking the body s RNA and DNA, helping to re-programme diseased cells. Ampligen up regulates enzyme systems, stimulating white blood cell chemical messengers. The product has been in development for many years for CSF and other indications including influenza, HIV, melanoma, renal carcinoma and hepatitis B. Innovation and/or advantages Ampligen is the first in a new class and if licensed would be the first specific pharmaceutical treatment for CFS/ME. Developer Hemispherx Biopharma. Place of use Home care e.g. home dialysis Secondary care e.g. general, non-specialist hospital General public e.g. over the counter Community or residential care e.g. district nurses, physio Tertiary care e.g. highly specialist services or hospital Other: Primary care e.g. used by GPs or practice nurses Emergency care e.g. paramedic services, trauma care Availability, launch or marketing dates, and licensing plans: A new drug application for Ampligen to treat CFS was filed in October in the USA a. Ampligen has been awarded orphan drug status in Europe and reports suggest that the company plan to file a licence application in the EU in next few months 1. NHS or Government priority area: This topic is relevant to the National Service Framework for Children and Maternity Services. Relevant guidance NICE clinical guideline: chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy), Department of Health: NHS Plus Evidence based guideline project. Occupational aspects of the management of chronic fatigue syndrome: a national guideline. October Department of Health: chronic fatigue syndrome/myalgic encephalopathy (CFS/ME), best practice guidance published alongside National Service Framework for children, young people and maternity services. December a 7 th December 2007, Hemispherx Biopharma press release: FDA has determined the application to be insufficiently complete 2

3 Royal College of Paediatrics and Child Health: Evidence based guideline for the management of CFS/ME (chronic fatigue syndrome/myalgic encephalopathy) in children and young people. December Clinical need and burden of disease CFS/ME comprises a range of symptoms that include fatigue, malaise, headaches, sleep disturbances, difficulties with concentration and muscle pain. A person s symptoms may fluctuate in intensity and severity over time, and there is a great variability in symptoms between people. CFS/ME is characterised by debilitating fatigue that is unlike everyday fatigue and can be triggered by minimal activity 2. There is a lack of epidemiological data for the UK. Evidence from other countries suggests a population prevalence of at least % (between 107,458 and 214,915 people in England and Wales) with approximately 25% patients severely affected (between 26,865 and 53,729 people in England and Wales) 6. Women are at higher risk of developing CFS/ME than men with a relative risk of Although CFS/ME can affect any age group, including children, it commonly presents in those in their twenties, thirties or forties 3. Existing comparators and treatments CFS/ME is managed using supportive care with treatment of specific symptoms as appropriate. Options include 2 : Sleep management Rest periods Relaxation Pacing Diet Cognitive behavioural therapy Graded exercise therapy Pain management. controlled Participants n=92; CFS/ME (meeting the Centre for Disease Control and Prevention (CDC) case definition). Randomised to Ampligen (n=45, 4 dropped out) or placebo (n=47, 4 dropped out). n=15; severe CFS/ME (diagnosed using CDC criteria). Received Ampligen. Follow-up 24 weeks weeks 6 months Primary Karnofsky performance KPS. KPS. outcome score (KPS). Efficacy and safety Status Published 8 Published 9 Unpublished 10 Conference abstract (American association for chronic fatigue syndrome, 1996) Location USA USA Belgium Design Randomised, double-blind Non-controlled open study Non-randomised, noncontrolled CFS/ME patients. Received Ampligen 200 mg or 400 mg twice weekly 3

4 Secondary outcomes Key results Adverse effects Perceived cognitive performance, activities of daily living (ADL), exercise treadmill. KPS % median change: Ampligen +20% vs. placebo 0% (p=0.023). Perceived cognitive deficit: Ampligen +27.3% vs. placebo +14.5% (p=0.05). ADL: Ampligen +23.1% vs. placebo +14.1% (p=0.034) Exercise duration: Ampligen +10.3% vs. placebo +2.1% (p=0.007) Exercise work: Ampligen +11.8% vs. placebo +5.8% (p=0.011) Adverse events were similar (Ampligen 706 vs. placebo 711). Statistically significant differences were found: insomnia (higher with placebo group) and dry skin (higher with Ampligen). IQ, memory, exercise tolerance. At 16 and 24 weeks, 23 and 54% increases respectively in memory scores (p=0.0032). Progressive increases in IQ (p=0.004). Average KPS score improved from 47 to 67 after 12 weeks of Ampligen therapy (p<0.001). Improvement in treadmill duration and oxygen uptake at week 24 of Ampligen therapy (p<0.001). - - Exercise performance, oxygen uptake. 80% experienced an apparent complete clinical recovery. KPS improved by 43% from 53 to 76. Oxygen uptake in exercise improved from 1.16 litres/minute to 1.48 litres/minute. Trial name or code NCT AMP 516 NCT AMP 511 Sponsor Hemispherx Biopharma Inc. Hemispherx Biopharma Inc. Status Completed, unpublished 11 Ongoing open to enrolment 12 Design Randomised, double-blind, placebocontrolled. Open-label, non-randomised, uncontrolled. Participants n= 234 severely disabling CFS/ME. Debilitating CFS/ME. Ampligen 400 mg iv twice weekly vs. placebo (normal saline). Follow-up 64 weeks Estimated cost and cost impact The cost of Ampligen is unknown. If licensed, there will be the additional costs for intravenous administration. Potential or intended impact speculative Patients Reduced morbidity Quicker, earlier or more accurate diagnosis or identification of disease Reduced mortality or increased survival Other: Improved quality of life for patients and/or carers Non identified Services Increased use Service reorganisation required Staff or training required Decreased use Other: Non identified 4

5 Costs Increased unit cost compared to alternative Increased costs: more patients coming for treatment Increased costs: capital investment needed New costs: Savings: Other: References 1 Scrip News. Hemispherex files first chronic fatigue syndrome candidate. PJB Publications. Number October 19 th Page National Institute for Health and Clinical Excellence. Chronic fatigue syndrome/myalgic encephalomyelitis (or encaphalopathy): diagnosis and management of CFS/ME in adults and Children. Guideline 53. August Department of Health: NHS Plus Evidence based guideline project. Occupational Aspects of the Management of Chronic fatigue syndrome: a national guideline. October Department of Health. Chronic Fatigue syndrome/myalgic encephalopathy (CFS/ME). National service framework for children, young people and maternity services. December Gateway ref Royal College of Paediatrics and Child Health. Evidence based guideline for the management of CFS/ME (Chronic Fatigue Syndrome/myalgic encephalopathy) in children and young people. December Shepherd C, Chaudhuri A. ME/CFS/PVFS: an exploration of the key clinical issues. The ME Association. 3 rd edition July Wessely S. The epidemiology of chronic fatigue syndrome. Epidemiologic Reviews 1995:17(1) Strayer DR, Carter WA, Brodsky I et al. A controlled clinical trial with a specifically configured RNA drug, polyi:polyc 12 U in chronic fatigue syndrome. Clinical Infectious Diseases 1994;18 (Suppl 1):S Strayer DR, Carter W, Strauss KI. Long term improvements in patients with chronic fatigue syndrome treated with Ampligen. Journal of Chronic Fatigue Syndrome 1995;1: Listening to CFIDS. Ampligen frequently asked questions. Hhttp://wwcoco.com/cfids/ampligen.htmlH. Submitted December 1996 (accessed 26/11/2007) 11 The Study of the Safety and Efficacy of Ampligen in Chronic Fatigue Syndrome. Hhttp:// NCT (accesses 23/11/07) 12 Study of Ampligen in Chronic Fatigue Syndrome. Hhttp://clinicaltrials.gov/H NCT (accessed 23/11/07) The National Institute for Health Research Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0) Fax +44 (0)