New Medicines

Mucopolysaccharidosis IIIA (MPS IIIA - Sanfilippo syndrome)


New molecular entity
Sarepta Therapeutics

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Jan 21Also has rare paediatric disease designation in the US [3].
Feb 20FDA grants fast track designation to LYS SAF302 for the treatment of MPS IIIA [3].
Oct 18Sarepta Therapeutics and Lysogene enter into a licensing agreement for LYS SAF302. Lysogene shall be responsible for completion of the pivotal trial. Sarepta shall have exclusive commercial rights to LYS SAF302 in the US and all territories outside of Europe, and Lysogene will retain exclusive commercial rights to LYS SAF302 in Europe [3].
Dec 17Granted orphan drug status in EU [3].
Nov 15Granted orphan drug status in US [3].


An adeno-associated viral vector serotype 10 (rAAVrh.10) carrying the human N-sulfoglucosamine sulfohydrolase (hSGSH). The missing gene SGSH is delivered directly to the CNS in a neurosurgical procedure to provide a permanent source of the missing enzyme.
Mucopolysaccharidosis III is considered the most common of the mucopolysaccharidosis genetic disorders, occurring with an incidence of 1 in 70,000 newborns. Sanfilippo syndrome results from the deficiency or absence of 4 different enzymes that are necessary to degrade the GAG heparan sulfate. Each enzyme deficiency defines a different subtype of Sanfilippo syndrome, as follows: type IIIA (Sanfilippo A), type IIIB (Sanfilippo B), type IIIC (Sanfilippo C), and type IIID (Sanfilippo D) [1].
Mucopolysaccharidosis IIIA (MPS IIIA - Sanfilippo syndrome)

Trial or other data

Oct 20Lysogene reports a death of a child patient in the AAVance trial. At the time of reporting, the reason of death was unknown and there was no evidence to establish causal relationship with the treatment of olenasufligene relduparvovec [3].
Jul 20The company received a letter from the US FDA confirming the clinical hold for recruitment and treatment of new patients in the AAVance trial. The US FDA issued a clinical hold for the trial in June 2020. The clinical hold follows observations in some patients of localised findings on MRI images at the intracerebral injection sites. The company has discussed a path forward with FDA and is looking to gather additional information on the drug ´s safety profile. As of June 2020, 19 out of 20 patients treated, and all patients remain in the study and are being followed per study protocol [3].
Dec 18Pivotal PII/III AAVance trial to assess the efficacy of olenasufligene relduparvovec (LYS SAF302) in improving or stabilising the neurodevelopmental state of MPS IIIA patients starts (NCT03612869; P078-2018; P4SAF302). The open-label trial is enrolling 20 patients aged 6 months and older in the US, UK, France, Netherlands and Germany. Primary outcome is change from baseline in development quotient (DQ), compared to regression reported in natural history studies at month 6, 12, 18, 24. Development Quotient will be measured for each patient using one of two standard instruments, the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) or the Kaufman Assessment Battery for Children, Second Edition (KABC-II), based on age and ability range. The development quotient (DQ) is a means to express a neurodevelopmental/cognitive delay which is computed as a ratio and expressed as a percentage using the development age (DA) score divided by the age at testing ([development age score/chronological age] × 100; range: 0 - 100, where high values are desirable). Collection of primary outcome data is due to complete Mar 22 [2].
Mar 17Lysiogene announces completion of the recruitment of 23 patients with MPS IIIA in an observational SAMOS study. The prospective natural history study intended to recruit patients who will not receive olenasufligene relduparvovec (LYS SAF302) but will receive study-related care. The results secured from the study will enable optimal trial design, greater understanding of disease progression and better predictions of future therapeutic effects of olenasufligene relduparvovec [3].