Clinical Hold Lifted on Homology’s pheNIX Trial for Phenylketonuria


The trial was placed on hold after elevated liver function test scores.

The FDA has lifted the clinical hold on Homology Medicines’ phase 1/2 pheNIX clinical trial (NCT03952156) of the gene therapy HMI-102 for the treatment of phenylketonuria (PKU).1

Homology has amended the trial protocol according to issues identified with the clinical hold, which was applied in February 2022 but clarified with a letter from the FDA in March 2022.2,3 The company will incorporate a new immunosuppression regimen with the T-cell inhibitor tacrolimus and a shorter course of steroids into the trial protocol.

"We believe our ability to quickly and successfully respond to the FDA is a testament to our experienced clinical and regulatory teams who also applied key learnings from the gene therapy field and our clinical program to update the pheNIX trial protocol," Albert Seymour, PhD, president and chief scientific officer, Homology Medicines, said in a statement.1 "We appreciate the FDA's active collaboration during this process, and we remain committed to bringing forward potential one-time treatments for people with PKU. Our plan is to provide an update on the program this fall."

The pheNIX trial was previously put on hold following elevated liver function test scores observed in the trial.2 These cases resolved without hospitalization. The company hopes that the modified immunosuppressive regimen, which is incorporated into their pheEDIT trial (NCT05222178) of HMI-103 in PKU and juMPStart gene therapy trial (NCT05238324) for Hunter syndrome, may also improve patient compliance.3 T-cell inhibitors have been shown to dampen the immune response to adeno-associated viruses (AAVs) in other clinical trials.

READ MORE: BioMarin’s PKU Gene Therapy On Hold Pending New Studies

The pheNIX study assesses 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 phenylalanine hydroxylase (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.

The HMI-102 gene therapy encodes the PAH gene and is delivered with the AAVHSC15 vector. The FDA has previously granted the therapy fast track and orphan drug designations, while the EMA has granted the therapy orphan drug designation.

Homology Medicines recently collaborated with Oxford Biomedica to create the manufacturing and innovation business, Oxford Biomedica Solutions LLC. The new business brings together Homology’s manufacturing capabilities with Oxford’s viral vector manufacturing experience. Homology also received $130 million for Oxford that will support their cash runway into 2024.

“As we move our clinical programs and pipeline forward, high-quality manufacturing from an industry-leading team remains one of our most important priorities,” Arthur Tzianabos, PhD, president and chief executive officer, Homology Medicines, said in a previous statement.4 “Our stake in Oxford Biomedica Solutions provides us with continued access to experts in our AAVHSC technology platform with the added benefits that our partnership with global viral vector manufacturing leader OXB can bring.”

1. Homology Medicines announces FDA lifted clinical hold on pheNIX gene therapy trial for PKU. News release. Homology Medicines. June 13, 2022.
2. Homology PKU Therapy Hit with Latest Trial Hold. News release. February 21, 2022. 
3. Homology Medicines Reports Fourth Quarter and Full Year 2021 Financial Results and Recent Highlights. News release. Homology Medicines. March 23, 2022.
4. Homology Medicines announces closing of deal leveraging its internal process development and CMC capabilities through newly formed AAV manufacturing innovation business with Oxford Biomedica. News release. Homology Medicines. March 10, 2022.
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