Bimagrumab for sporadic inclusion body myositis – first line

September 2015

Horizon Scanning Research & Intelligence Centre

Bimagrumab for sporadic inclusion body myositis ? first line

This briefing 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 or commissioning without additional

information.

LAY SUMMARY

Sporadic inclusion body myositis is a rare disease that affects the muscles of older people. It causes weakness and can lead to difficulties standing and walking safely without falling. There is currently no treatment for this disease.

Bimagrumab is a new drug being developed for sporadic inclusion myositis. It is given straight into the blood stream through a drip once every 4 weeks. A study is currently running to see how well it works to improve patients' walking abilities and to see if it is safe to use.

If it is licensed for use in the UK, bimagrumab will be the first treatment available for people with sporadic inclusion body myositis.

NIHR HSRIC ID: 8195

This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health.

NIHR Horizon Scanning Research & Intelligence Centre, University of Birmingham. Email: nihrhsc@contacts.bham.ac.uk Web: hsric.nihr.ac.uk

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TARGET GROUP

? Sporadic inclusion body myositis: ambulatory patients ? first line.

TECHNOLOGY

DESCRIPTION

Bimagrumab (BYM 338; BYM-338; BYM338) is a fully human monoclonal antibody which competitively binds to the activin receptor type II (ActRII), thereby preventing the binding and subsequent signalling of its ligands, including myostatin and activin. This is thought to lead to an increase in muscle mass and strength. In phase IIb/III clinical trials, bimagrumab was administered at 1mg/kg, 3mg/kg, or 10mg/kg intravenously (IV) every 4 weeks.

Bimagrumab is currently in phase II trials for cachexia and muscular atrophy in the elderly. Bimagrumab is not currently licensed in the EU for any indication.

INNOVATION and/or ADVANTAGES

If licensed, bimagrumab will provide the first treatment option specifically licensed for patients with sporadic inclusion body myositis.

DEVELOPER

Novartis Pharmaceuticals UK Ltd.

AVAILABILITY, LAUNCH OR MARKETING

In phase II/III clinical trials.

PATIENT GROUP

BACKGROUND

Sporadic inclusion body myositis is an acquired muscle disorder associated with ageing, for which there is no effective treatment1. Sporadic inclusion body myositis is considered to be the most common acquired muscle disease causing weakness and atrophy of the distal and proximal muscles2. Sporadic inclusion body myositis is traditionally classified as an idiopathic inflammatory myopathy, along with polymyositis and dermatomyositis3. However, the pathological process is also characterised by a significant degenerative component exemplified by intramuscular accumulation of misfolded proteins including amyloid4,5. The true pathogenesis of the disease remains a subject of significant debate. Possibilities include a primary T-cell mediated autoimmune response causing muscle damage, a primary degenerative process involving abnormal protein processing leading to a secondary inflammatory response, a combination of these pathological processes, or a separate and independent immune and degenerative process caused by an external trigger6.

Signs and symptoms of sporadic inclusion body myositis include frequent falling episodes, trouble climbing stairs or standing from a sitting position, weakened hand grip and difficulty swallowing7.

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NHS or GOVERNMENT PRIORITY AREA

This topic is relevant to: ? NHS England. 2013/14 NHS Standard Contract for Specialised Rheumatology (Adult).

A13/S/a.

CLINICAL NEED and BURDEN OF DISEASE

Sporadic inclusion body myositis has a male predominance and usually does not affect individuals below the age of 45. Estimates for the prevalence of the disease range widely from of 1-71 per million, reaching 139 per million in those over the age of 501. In 2012, the most likely estimate for the population prevalence of inclusion body myositis in the European Union (EU) was considered to be approximately 5 per million8.The rarity of the disease, lack of patient and clinical awareness, and diagnostic difficulties contribute to a substantial delay between the onset of symptoms and diagnosis (five-year delay on average)9. In 2013-14, there were 209 admissions for sporadic inclusion body myositis (ICD10 G72.4) in England and Wales resulting in 1,246 bed days and 209 finished consultant episodes10.

PATIENT PATHWAY

RELEVANT GUIDANCE

NICE Guidance

? None identified.

Other Guidance

? None identified.

CURRENT TREATMENT OPTIONS

There is no cure for sporadic inclusion body myositis and the disorder generally does not respond to conventional therapies for autoimmune disorders such as corticosteroids or immunosuppressive drugs11. However, some individuals respond to these therapies for a short period of time or to a minor degree (i.e. there is not a full recovery of muscle strength). Immunosuppressive drugs that have been used to treat sporadic inclusion body myositis include azathioprine, methotrexate, cyclosporine, and cyclophosphamide9. However, expert comments suggest this approach is usually unsuccessfula.

Specific treatment options for affected individuals may include physical and occupational therapy to improve muscle strength and, when necessary, the use of various devices including braces, walkers or wheelchairs to assist with walking9.

a Expert personal opinion.

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EFFICACY and SAFETY

Trial Sponsor Status Source of information Location Design Participants

Schedule

Follow-up Primary outcome/s Secondary outcome/s

Expected reporting date

NCT01925209, RESILIENT; bimagrumab vs placebo; phase II/III. Novartis Pharmaceuticals. Ongoing. Trial registry12.

EU (incl UK), USA, Australia, and other countries. Randomised, placebo-controlled. n=240; aged 36-85 years; diagnosed with sporadic inclusion body myositis; able to walk (assistive aids allowed, including intermittent use of wheelchair).

Randomised to either bimagrumab 1mg/kg, 3mg/kg, or 10mg/kg administered IV every 4 weeks; or placebo IV every 4 weeks. Active treatment up to 104 weeks. Change from baseline in 6 minutes walking distance test (6MWD) to week 52.

Change from baseline in lean body mass (LBM) at 52 weeks; change from baseline in quadriceps quantitative muscle testing (QMT) 52 weeks; change from baseline in patient-reported physical function at 52 weeks; rate of fall events over 108 weeks. The sporadic inclusion body myositis functional assessment (SIFA) instrument was used to measure physical function. This is a self-administered questionnaire which assesses the impact of upper, lower, and general physical functioning and consists of 11 items (0-10 increasing disability). Study completion date reported as December 2015.

ESTIMATED COST and IMPACT COST The cost of bimagrumab is not yet known. IMPACT - SPECULATIVE

Impact on Patients and Carers

Reduced mortality/increased length of survival Reduced symptoms or disability

Other:

No impact identified

Impact on Health and Social Care Services

Increased use of existing services

Decreased use of existing services

Re-organisation of existing services

Need for new services

Other:

None identified

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Impact on Costs and Other Resource Use

Increased drug treatment costs Other increase in costs: increase in resource

use for administration by infusion. Other:

Reduced drug treatment costs

Other reduction in costs: reduction in cost of treatments of falls, etc.

None identified

Other Issues

Clinical uncertainty or other research question None identified identified:

REFERENCES

1 Machado P, Ahmed M, Brady S et al. Ongoing developments in sporadic inclusion body myositis. Current Rheumatology Reports 2014;16:477.

2 Machado O, Miller A, Holton J et al. Sporadic inclusion body myositis: an unsolved mystery. Acta Rheumatologica Portugesa 2009;34:161-82.

3 Dalakas MC. Inflammatory disorders of muscle: progress in polymyositis, dermatomyositis and inclusion body myositis. Current Opinion in Neurology 2004;17:561-567.

4 Askanas V and Engel WK. Inclusion-body myositis: muscle-fiber molecular pathology and possible pathogenic significance of its similarity to Alzheimer's and Parkinson's disease brains. Acta Neuropathology. 2008;116(6):583-95.

5 Greenberg SA. Biomarkers of inclusion body myositis. Current Opinions in Rheumatology. 2013;25(6):753-62.

6 Medscape. Inclusion Body Myositis. emedicine.article/1172746-overview#a5 Accessed 27 August 2015.

7 The Myositis Association. Inclusion-Body Myositis. learn-about-myositis/typesof-myositis/inclusion-body-myositis Accessed 20 August 2015.

8 European Medicines Agency. Human medicines. Rare disease designations. EU/3/12/1035. ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/orphans/2012/09/humanorpha n_001119.jsp&mid=WC0b01ac058001d12b Accessed 25 August 2015.

9 Benveniste O, Guiguet M, Freebody J et al. Long-term observational study of sporadic inclusion body myositis. Brain A Journal of Neurology 2011;134:3176?84.

10 Health and Social Care Information Centre. Hospital episode statistics for England. Inpatient

statistics, 2013-14. .uk 11 National Organisation for Rare Disorders. Sporadic inclusion body myositis.

rare-diseases/sporadic-inclusion-body-myositis Accessed 25 August 2015. 12 . Efficacy and safety of bimagrumab/BYM338 at 52 weeks on physical function,

muscle strength, mobility in sIBM patients (RESILIENT). ct2/show/NCT01925209 Accessed 25 August 2015.

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