MPS 2 Systemic Gene Therapy Evaluated in New Trial

October 29, 2021

Article

The FDA cleared the IND application for HMI-203 in October 2021.

Homology Medicines has initiated the phase 1 juMPStart trial of the gene therapy HMI-203 for the potential treatment of mucopolysaccharidosis type 2 (MPS 2), or Hunter syndrome.

“We are excited to start the Phase 1 trial for HMI-203, our investigational gene therapy for Hunter syndrome, as our team remains dedicated to improving outcomes for the patient community since our prior work developing ERT,” said Arthur Tzianabos, PhD, president and chief executive officer, Homology Medicines, in a statement. “With today’s milestone, we have also accomplished our goal of having 3 clinical programs by the end of 2021, with our gene therapy and gene editing clinical trials for PKU and the initiation of the juMPStart trial for Hunter syndrome. We are executing on this and our other programs, and we look forward to our continued collaboration with the MPS II community.”

The open-label, dose-escalation juMPStart trial is evaluating the safety and efficacy of a single intravenous administration of HMI-203. The trial is expected to enroll up to 9 male patients with MPS 2 between the ages of 18 and 30 years currently receiving enzyme replacement therapy (ERT). The trial will primarily assess safety endpoints but will also evaluate efficacy by measuring plasma I2S activity, urinary GAG levels and other peripheral disease manifestations. The trial will evaluate 3 doses of HMI-203 as part of the dose-escalation that will lead to a potential phase 2 trial. The FDA cleared the investigational new drug application for HMI-203 in October 2021, enabling the trial to initiate.

“I am pleased to work with the Homology team, as we both have a long-held and shared commitment to the MPS II community and a focus on bringing forward a one-time gene therapy to address the underlying cause of this disease,” Joseph Muenzer, MD, PhD, Bryson Distinguished Professor, pediatric genetics, University of North Carolina at Chapel Hill, added to the statement. “While weekly intravenous ERT has made a huge difference for the MPS II community, it is very time-consuming and there remains the need to address the brain disease in the severe or neuronopathic form of MPS II. I am optimistic that Homology’s gene therapy approach for MPS II could make a significant impact on all aspects of the disease, including the peripheral manifestations, as well as the day-to-day lives of patients and their families, and I look forward to working with the Homology team and all of the investigators in the HMI-203 clinical trial to evaluate this approach.”

HMI-301 is an in-vivo gene therapy candidate in development by Homology Medicines. It is designed to use 1 of the company’s human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to deliver functional copies of the IDS gene to organs with missing or mutated copies of the gene. This enables break down of glycosaminoglycans (GAGs) by restoring production of the I2S enzyme. While many patients with MPS 2 currently receive ERT to replace the I2S enzyme, there still remains a high unmet medical need for patients with MPS 2.

“We are pleased to be transitioning HMI-203 into the clinic for patients, building on the positive preclinical data we presented at scientific conferences, including the upcoming ASHG meeting. These data showed long-term expression of I2S in multiple organs, sustained secretion in the serum, reduced GAGs in all tissues tested as well as the cerebrospinal fluid, and phenotypic correction in the Hunter disease murine model following a one-time administration. We appreciated the insights from the Hunter syndrome community as we designed our clinical program, and we look forward to continuing our work together as we advance juMPStart,’ Albert Seymour, PhD, chief scientific officer, Homology Medicines, added to the statement.