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37504611000001104

New Medicines

Onpattro Hereditary transthyretin amyloidosis (ATTR) - progression after liver transplant

Information

Onpattro
Licence extension / variation
Alnylam Pharmaceuticals
Alnylam Pharmaceuticals

Development and Regulatory status

None
Pre-registration (Filed)
Phase III Clinical Trials
Yes
Yes
Aug 21EMA CHMP starts reviewing the application to change labelling to include data from NCT03862807 study [5].
Jun 21Alnylam expects data from PIIIb NCT03862807 study to form the basis of post-approval supplements to change labelling for Onpattro where approved, including in the EU [4].
Jan 21Has orphan drug status in EU and US for amyloidosis [3].

Category

Systemically delivered RNA interference therapy
Orthotopic liver transplantation (OLT) is used as a therapy for TTR amyloidosis. Survival after transplant may be associated with progression of neuropathy due to continued deposition of amyloid derived from wild-type TTR. More than 1,500 patients have had OLT for TTR amyloidosis. Data collected by the Familial Amyloidotic Polyneuropathy World Transplant Register show patients with the Val30Met mutation have a 5-year survival of 80%, in those with other mutations it is only 50-60% [1].
Hereditary transthyretin amyloidosis (ATTR) - progression after liver transplant
Oral

Trial or other data

Jun 21In PIIIb trial, median reduction in serum TTR levels compared to baseline was 91 percent, measured as an average of the month six and month 12 reduction. At month 12, patisiran treatment resulted in a 3.7 point decrease in mean total neurological impairment (NIS) score, a 6.5 decrease in mean total Norfolk Quality of Life-Diabetic Neuropathy score (Norfolk QOL-DN) and a 5.0 decrease in the least squares (LS) mean total COMPASS-31 score from baseline [4].
Oct 20PIIIb trial (NCT03862807) completes collection of primary outcome data [2].
May 20Results released for the PIIIb trial (NCT03862807) show that in 23 patients with hATTR amyloidosis and disease progression after receiving an OLT, treatment with patisiran after three weeks demonstrated mean reduction of 81.9% from baseline in serum TTR levels [3].
Mar 19PIIIb trial to assess the efficacy, safety and pharmacokinetics of patisiran in patients with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with disease progression (increase in polyneuropathy disability (PND) score) after liver transplant starts (NCT03862807; ALN-TTR02-008). 24 adults will be enrolled in Sweden, France, Portugal, Italy, Germany, Spain and UK. Primary endpoint is to determine the six month and 12 month average reduction of serum transthyretin (TTR) from baseline [2].

Onpattro Transthyretin amyloidosis (ATTR) with cardiomyopathy

Information

Onpattro
Licence extension / variation
Alnylam Pharmaceuticals
Alnylam Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

Systemically delivered RNA interference therapy
The clinical prevalence of wild-type ATTR cardiomyopathy is unknown, but autopsy studies suggest that up to 22-25% of indi- viduals >80 years old have demonstrable TTR amyloid deposits in cardiac tissue, although in most cases the degree of deposition is mild [1].
Transthyretin amyloidosis (ATTR) with cardiomyopathy
Oral