Second Phenylketonuria Gene Therapy Study Put on Clinical Hold
The pheNIX clinical hold follows an announcement that BioMarin’s PKU hold may last several quarters.
The FDA has placed a
Homology will have to modify the study’s risk mitigation measures to prevent any serious issues that may arise, although the company has not yet received a formal letter of clinical hold, so clearer directives by the FDA are forthcoming.
The pheNIX study is primarily 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 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 which is delivered via the AAVHSC15 vector. The FDA previously granted the therapy fast track and orphan drug designations, while the EMA has granted the therapy orphan drug designation.
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In October 2021, Homology announced updated safety data from the trial that both doses were well-tolerated with promising initial efficacy data including clinically meaningful reductions in Phe levels as well as increases in Tyr and reductions in the Phe-to-Tyr ratio.2 At that time, the trial had been expanded to include a total of 13 clinical trial sites.
"This hold on our PKU gene therapy trial is based on clinical observations in the pheNIX study and does not relate to CMC/manufacturing capabilities or Homology's other clinical programs. We plan to provide next steps once we have more information following our FDA interactions," Arthur Tzianabos, PhD, president and chief executive officer, Homology, said in a statement.1
Unaffected by the clinical hold is Homology’s other trial in PKU, the pheEDIT trial of their gene-editing therapy HMI-103. HMI-103 uses the same viral vector as HMI-102, but unlike HMI-102, HMI-103 uses homologous recombination to insert a functional PAH gene into the genome of liver cells while also inactivating at least 1 of the mutated genes to induce PAH expression in liver cells and restore metabolism of Phe.2
The pheEDIT trial was
Homology’s clinical hold follows that of another gene therapy in the PKU space, BioMarin’s BMN-307 and its phase 1/2 PHEARLESS study (NCT04480567). The study seems likely to be on
REFERENCES
1. 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-/
2. Homology Medicines announces world’s first gene editing clinical trial for PKU. News release. Homology Medicines. October 12, 2021. https://www.homologymedicines.com/news-story/homology-medicines-announces-worlds-first-gene-editing-clinical-trial-for-pku
3. BioMarin Provides Updates on Progress in Gene Therapy Programs. News release. Biomarin. Feburary 17, 2022. https://www.prnewswire.com/news-releases/biomarin-provides-updates-on-progress-in-gene-therapy-programs-301484779.html
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