Homology Trades in Gene Delivery for Gene Editing to Treat Phenylketonuria


The pheEDIT clinical trial initiated in June 2022.

Homology Medicines has paused enrollment in its phase 1/2 pheNIX clinical trial (NCT03952156) of the gene therapy HMI-102 for the treatment of phenylketonuria (PKU), the company revealed 2 months after announcing that a clinical hold had been lifted from the program.1,2

The company is deprioritizing the HMI-102 gene therapy in favor of its gene editing therapy, HMI-203, which is being evaluated in the phase 1/2 pheEDIT trial (NCT05222178) that initiated in June.1 HMI-103 is designed to induce phenylalanine hydroxylase (PAH)expression in liver cells and restore metabolism of Phe. The gene is delivered via the AAVHSC15 vector and homologous recombination inserts a functional PAH gene into the genome while also inactivating at least 1 of the mutated genes. HMI-102 encodes the PAH gene and is delivered with the same vector.

The FDA has previously granted HMI-102 fast track and orphan drug designations (ODD), while the EMA has granted the therapy orphan drug designation. HMI-203 also recently received ODD.

“Homology has a strong cash position that is now expected to take us into the fourth quarter of 2024. The extended cash runway is, in part, based on our recent strategic decision to divert our resources to the ongoing pheEDIT clinical trial evaluating gene editing candidate HMI-103 in adults with PKU, while pausing enrollment in our HMI-102 pheNIX gene therapy trial that was recruiting for the same patient population,” Arthur Tzianabos, PhD, chief executive officer, Homology Medicines, said in a statement.1 “We believe this, together with additional steps that we are taking, including plans to partner our optimized MLD gene therapy program, will position the Company well to move select programs forward to near-term catalysts while focusing our resources and conserving cash. We continue to expect to provide program updates on pheEDIT and our Hunter syndrome gene therapy trial, juMPStart, at the end of the year.”

READ MORE: In Vivo Gene Therapy Candidate for Metachromatic Leukodystrophy in Development

The pheNIX trial was previously placed on clinical hold following elevated liver function test scores in participants that later resolved without hospitalization.3 In response, Homology adopted a modified immunosuppressive regimen that was incorporated into pheEDIT and juMPStart to improve patient compliance and the hold was lifted in June 2022.2,4

The trial is assessing the safety of HMI-102 via treatment-related adverse events (AEs), liver function tests, electrocardiograms, and plasma Phe concentration in adults with classical PKU due to PAH deficiency. Participants receive a single intravenous administration of HMI-102 and are observed for 52 weeks plus an additional 4 years of follow-up to ensure stability.

“While we continued to see biologic activity in our pheNIX gene therapy trial for PKU, we believe focusing our efforts on the gene editing program for PKU is the best approach for the Company at this time. This was confirmed at the recent ASGCT Meeting where we shared the unique mechanism of action of HMI-103, including data showing durability and increased expression in preclinical models, coupled with the potential to treat adults and ultimately younger patients,” Albert Seymour, PhD, president and chief scientific officer, Homology Medicines, added to the statement.1 “With several sites currently active and open for enrollment, we believe we can more rapidly progress recruitment for the pheEDIT trial, which will evaluate a steroid-sparing immunosuppressive regimen, including a T-cell inhibitor, versus the time it would take to resume enrollment of the pheNIX trial. We also continued to advance HMI-104, which uses our GTx-mAb technology, into IND-enabling studies. This program represents a third part of Homology’s platform, and we believe it provides the opportunity to address potentially larger market indications.”

1. Homology Medicines reports second quarter 2022 financial results, recent highlights and provides business update. News release. Homology Medicines. August 15, 2022. https://www.globenewswire.com/news-release/2022/08/15/2498571/0/en/Homology-Medicines-Reports-Second-Quarter-2022-Financial-Results-Recent-Highlights-and-Provides-Business-Update.html
2. Homology Medicines announces FDA lifted clinical hold on pheNIX gene therapy trial for PKU. News release. Homology Medicines. June 13, 2022. https://firstwordpharma.com/story/5593479/
3. Homology PKU Therapy Hit with Latest Trial Hold. News release. February 21, 2022. https://www.biospace.com/article/homology-pauses-clinical-trial-on-potential-pku-drug-/
4. Homology Medicines Reports Fourth Quarter and Full Year 2021 Financial Results and Recent Highlights. News release. Homology Medicines. March 23, 2022. https://investors.homologymedicines.com/news-releases/news-release-details/homology-medicines-reports-fourth-quarter-and-full-year-2021
Related Videos
Leigh Ramos-Platt, MD, on Looking Forward to Gene Therapy’s Growth
Sowmya Viswanathan, PhD, on Translating Cell Therapies to the Clinic at ISCT 2024
Omer A. Abdul Hamid, MD, on Improving Gene Therapy’s Effect and Accessibility
Jacques Galipeau, MD, on Highlights from ISCT 2024’s Presidential Plenary
Robert J. Hopkin, MD, on Looking Deeper into Fabry Disease Biology
Alessandro Aiuti, MD, PhD, on Durable, Clinically Meaningful Efficacy of Arsa-Cel in Metachromatic Leukodystrophy
Zheng-Yi Chen, DPhil, on International Collaboration on Clinical Trials
Maria Escolar, MD, the chief medical officer of Forge Biologics
John Murphy, PhD, the chief scientific officer of Arbor Biotechnologies
Maria Escolar, MD, the chief medical officer of Forge Biologics
© 2024 MJH Life Sciences

All rights reserved.