dm+d

Unassigned

New Medicines

Mucopolysaccharidosis II (MPS II - Hunter syndrome) in adults and adolescents aged >12 years

Information

New molecular entity
Sangamo
Sangamo

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Phase II Clinical Trials
Yes
Yes
Jun 19Recruitment completed for NCT03041324 trial; estimated primary completion Feb 2021 [5].
Dec 18Sangamo Therapeutics announced plans to expand PI/II CHAMPION trial into the UK in late 2018.[2]
Dec 17Committee for Orphan Medicinal Products of the EMA issued a positive opinion on the application for orphan medicinal product designation for SB 913 for treatment of mucopolysaccharidosis II.[2]
Jul 17US FDA granted Fast Track designation to SB 913 for the treatment of mucopolysaccharidosis II.[2]
May 17Rare paediatric disease designation for SB 913 for the treatment of mucopolysaccharidosis II in US.[2]
Mar 17US FDA granted orphan drug designation to SB 913 for the treatment of mucopolysaccharidosis II/[2]

Category

Recombinant corrective iduronate 2-sulfatase (IDS) transgene, given as single i.v. infusion under control of the highly expressed endogenous albumin locus to restrict endogenous gene editing to pts own hepatocytes.[2]
MPS II typically affects ~ 1 in 100,000 to 1 in 170,000 male births. A few affected females have been described. Symptoms usually become apparent at ~2-4 years of age. [1]
Mucopolysaccharidosis II (MPS II - Hunter syndrome) in adults and adolescents aged >12 years
Intravenous infusion

Trial or other data

Nov 20No activity reported in PI/II study (NCT03041324) since Dec 19 (which is due to complete in Feb 22). However, a non-interventional, multi-centre, long-term follow-up (LTFU) study of subjects dosed with SB-318 in the clinical study SB-318-1502, SB-913 in the clinical study SB-913-1602, and SB-FIX in clinical study SB-FIX-1501 starts (NCT04628871). 13 patients will be enrolled and followed until Jan 2030 [6].
Apr 19SB 913 is delivered as a a single intravenous infusion via recombinant adeno-associated virus serotype 6 (rAAV2/6) to insert the corrective copy of the IDS transgene into the genome of the patient ´s own hepatocytes, under the control of the highly expressed endogenous albumin locus. This way editing is restricted to liver cells. The ability to permanently and precisely integrate the therapeutic IDS gene into the DNA differentiates Sangamo´s in vivo genome editing approach from conventional AAV cDNA gene therapy and from lenti- or retroviral-based gene therapies that insert genes randomly into the genome [2].
Apr 19Sangamo plans to begin a new trial of SB-19 in the H2 2019 to make a phase 3 decision for the SB-913 program in 2020.[3]
Dec 18Interim results from the PI/II CHAMPIONS trial showed 8.9%, 4.1% and -23.5% change in total glycosaminoglycans, dermatan sulfate and heparan sulfate at 16 weeks, respectively, in cohort 1. In cohort 2, change in total glycosaminoglycans, dermatan sulfate and heparan sulfate at 16 weeks was found to be -50.8%, -31.8% and -61.5%, respectively. However, in 5/6 pts enrolled in the study, IDS activity and GAG levels scarcely changed in the 24 weeks following administration of SB-913. Data will continue to accumulate throughout 2019 and further updates on these studies are expected.[2-4]
Aug 18Six pts have received treatment in PI/II dose-ranging, open label CHAMPIONS trial (SB-913-1602; NCT03041324), designed to evaluate the safety, preliminary efficacy and tolerability of ascending doses of SB 913 in patients with mucopolysaccharidosis II.[2]