Patisiran approved in Europe and the US for the treatment of polyneuropathy in adults with hereditary TTR amyloidosis
Patisiran is a novel agent that has been approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for treating polyneuropathy in adults caused by hereditary transthyretin (TTR) amyloidosis. [65] It is one of a new class of drugs called small interfering ribonucleic acid (siRNA) treatments, which work by silencing specific genes. Patisiran inhibits the production of TTR in the liver. It is the second of its class to be approved in Europe for this indication (inotersen was approved by the EMA in July 2018). It is the first therapeutic of its class to be approved in the US.
Approval was based on the results of an 18-month randomised placebo-controlled phase III trial (APOLLO). In the trial, patisiran reduced neurological impairment and improved quality of life compared with placebo in patients with TTR amyloidosis with polyneuropathy. The incidence and severity of adverse events were similar in patients receiving patisiran and placebo.
TTR amyloidosis is the most common form of inherited amyloidosis. It is a progressively debilitating disease that can lead to death. Liver transplantation is considered standard of care for these patients; however, this is limited to those who are fit enough for transplantation and who have a suitable donor. Patisiran provides clinicians with an alternative treatment option to liver transplantation in patients with TTR amyloidosis.
See Management: approach See Management: treatment algorithmSummary
Definition
History and exam
Key diagnostic factors
- presence of risk factors
- jugular venous distention
- lower extremity oedema
- periorbital purpura
- macroglossia
Other diagnostic factors
- fatigue
- weight loss
- dyspnoea on exertion
- paraesthesia
- claudication
- nausea
- abdominal cramps
- alternating bowel habit
- light-headed/orthostatic hypotension
- submandibular salivary gland enlargement
- hepatomegaly
- shoulder pad sign
- diffuse muscular weakness
- sensory neuropathy
- Tinel's sign
- Phalen's manoeuvre
Risk factors
- monoclonal gammopathy of undetermined significance (MGUS)
- inflammatory polyarthropathy
- chronic infections
- inflammatory bowel disease
- Castleman's disease
- familial periodic fever syndromes
Diagnostic investigations
1st investigations to order
- serum immunofixation
- urine immunofixation
- immunoglobulin free light chain assay
- bone marrow biopsy
Investigations to consider
- tissue biopsy
- immunohistological studies of amyloid deposits
- mass spectrometry
- immuno-electron microscopy
- genetic testing
- serum amyloid P (SAP) scintigraphy scan
- FBC
- comprehensive metabolic profile
- 24-hour urine collection
- serum troponin level
- B-type natriuretic peptide
- beta-2-microglobulin
- ECG
- echocardiogram
- Doppler echo with strain
- cardiac MRI
Treatment algorithm
Contributors
Authors VIEW ALL
Seidler Jr. Professor of Medicine
Consultant in Hematology
Chair Emeritus of the Department of Medicine
Mayo Distinguished Clinician
Mayo Clinic College of Medicine
Rochester
MN
Disclosures
MAG declares that he has received honoraria from Celgene Corporation, Prothena Corporation Plc, Onyx Pharmaceuticals, Alnylam, and Ionis Pharmaceuticals. MAG is also an author of several references cited in this monograph.
Peer reviewers VIEW ALL
Associate Professor of Medicine
Director
Program for Multiple Myeloma and Related Diseases
Princess Margaret Hospital
Toronto
Ontario
Canada
Disclosures
DR has been reimbursed by Millennium Pharmaceuticals, Inc and Johnson and Johnson, the manufacturers of bortezomib, for attending several conferences, for speaking at educational meetings, and for consulting work. She has also been reimbursed by Celgene, the manufacturer of lenalidomide and thalidomide, for attending several symposia and serving as a speaker.
Assistant Professor of Medicine and Oncology
Division of Hematology/Oncology
Wayne State University School of Medicine
Barbara Ann Karmanos Cancer Institute
Detroit
MI
Disclosures
JZ declares that he has no competing interests.
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