SOBI Sanfilippo type A enzyme replacement trial results published

04 Aug 2022

Results from a clinical trial to evaluate the safety and effectiveness of SOBI003, a modified sulfamidase enzyme, in patients with Sanfilippo type A have been released

Sponsored by Swedish Orphan Biovitrum (SOBI), an initial phase I/II trial commenced in June 2018 and treated six patients with Sanfilippo type A. This was followed by an extension study around a year later, which followed the same six patients as they continued to receive the therapy at a higher dose. In heartbreaking news to families and supporters, SOBI decided to halt the program due to business reasons in 2020, and the program was officially discontinued in April 2021.

The SOBI003 enzyme replacement therapy (ERT) was modified to be able to cross the blood-brain barrier. This meant it could be delivered intravenously, making its administration less invasive compared to some ERT trials which deliver the therapy directly into the fluid-filled space in the brain via a port.

Patients in the trial were aged between 15-65 months at the time of the first infusion with SOBI003, with a median age of 36 months. To first establish safety, they were initially separated into two groups that received either a 3 mg/kg or 10 mg/kg dose of the drug weekly via intravenous injection. In the extension study, five patients increased their dose to 20 mg/kg.

The recently-released data demonstrates that SOBI003 was generally well-tolerated in patients. No patient experienced any serious adverse event associated with the therapy, though some mild to moderate adverse events, like skin rash and increased heartbeat, were seen.

The results confirm that SOBI003 was able to cross the blood-brain barrier: the therapy was detected in both the blood serum and the cerebrospinal fluid (CSF), which is the fluid that bathes the brain and spinal cord.

Antibodies to SOBI003 were seen in blood serum and CSF in all patients, indicating the patient’s immune system had detected the enzyme as ‘foreign’ and was trying to remove it from the body. It is known that these antibody responses can potentially reduce the efficacy of a treatment.

However, encouraging reductions in heparan sulfate levels were seen in the CSF of the majority of patients, reaching a maximum reduction of 79% from pretreatment levels after two years of treatment. HS levels were also reduced in the serum and urine. 

While there were too few patients in the study for the investigators to reach clear conclusions about the clinical efficacy of the therapy, the overall results indicated a stabilisation in cognitive development amongst the younger patients in the study. Despite this, and despite anecdotal reports of improvements noted by parents, there was no significant improvement seen in terms of overall quality of life, adaptive behaviour, and sleep.

The early termination of the SOBI003 program was a great disappointment to the Sanfilippo community. However, the publication of the data allows the Sanfilippo research community to learn a great deal from the study results to benefit future therapy development and clinical trial design. The study authors note the need to consider additional measurements in future trials that assess outcomes of importance to families, as well as the need for newborn screening programs to enable the earliest possible treatment for children born with Sanfilippo syndrome.