Homology Medicines Announces Presentation of Positive Data from the Dose-Escalation Phase of the pheNIX Gene Therapy Trial for Adults with PKU
- Marked Reductions in Phe Observed at Two Doses -
- Achieved Goal with Plans to Advance to Randomized, Concurrently Controlled Expansion Phase of Trial -
- Webcast / Conference Call Today, November 6 at 4:30 p.m. ET -
The data were presented today in an oral presentation by
“This is the first-ever PKU gene therapy clinical trial, and I am excited to share these data with the PKU community as I believe they demonstrate the potential of HMI-102 to treat the underlying genetic cause and reduce the therapeutic burden for patients and their families,” stated
“We are pleased to have met the goals of the dose-escalation portion of the trial, which were evaluation of safety and efficacy of a single I.V. administration of HMI-102 and dose determination for the expansion phase of the trial,” stated
As of the data cutoff date of
HMI-102 was generally well-tolerated, and there were no treatment-related serious adverse events (SAEs). There were no clinically significant changes in ECG or vital signs and no clinical signs of complement activation. The Grade 1 and 3* alanine aminotransferases (ALTs) observed in Cohorts 2 and 3, which is common in AAV-based gene therapy, were managed with increased steroids when necessary. The patients who experienced Grade 3 ALTs had pre-existing underlying immune conditions. An independent data monitoring committee, which provided guidance throughout the pheNIX trial, concluded that there were no safety concerns related to bilirubin, and that ALT elevations may be associated with reduced efficacy.
Updates to the expansion phase of the pheNIX trial, including key learnings related to patient selection, monitoring and steroid regimen, are being incorporated.
Cohort 1 (Low-Dose)
Through 52 weeks, patients in Cohort 1 continued to show no meaningful reductions in Phe.
Cohorts 2 and 3 (Mid- and High-Dose)
The mean percent change from baseline in Phe observed in patients in Cohorts 2 and 3 were significant, compared to Cohort 1**. These Phe reductions occurred while patients self-liberalized their diets.
Through 48 weeks, one patient in Cohort 2 had Phe levels of <360 μmol/L and/or <600 μmol/L*** at multiple timepoints and had reached a minimum Phe level of 42 μmol/L, compared with a baseline level of 1,010 μmol/L. Through 13 weeks, one patient in Cohort 3 had a Phe level <360 μmol/L and several Phe levels <600 μmol/L at multiple timepoints and had reached a minimum Phe level of 303 μmol/L, compared with a baseline level of 1,060 μmol/L.
In Cohorts 2 and 3, Phe reductions were greater among patients with Grade 1 ALTs compared to patients with Grade 3 ALTs****; ALT elevations were managed with increased steroids when necessary. It appears higher ALT elevations may limit therapeutic activity, but can be managed with a modified steroid regimen, which is being incorporated into the expansion phase.
Based on the safety and efficacy results observed in the dose-escalation phase, Homology is advancing to the randomized, concurrently controlled, dose expansion phase of the pheNIX trial, which has the potential to be converted to a registrational trial.
All cohorts in the dose-escalation phase showed an acceptable safety profile and certain patients in Cohorts 2 and 3 showed marked Phe reductions. Based on these collective data, Homology has selected two doses for the expansion phase: the mid-dose from Cohort 2 and a dose between the doses in Cohorts 2 and 3. The Company believes the latter dose has the potential to improve Phe reductions while reducing steroid exposure that was required at the high-dose. The Company believes that advancing two doses in parallel provides the potential to convert to a registrational trial quickly with the optimal dose as the expansion phase does not include staggered dosing between patients.
Homology management and
HMI-102 is an investigational gene therapy in clinical development for the treatment of phenylketonuria (PKU) in adults. HMI-102 is designed to encode the PAH gene, which is mutated in people with PKU, delivered via the liver-tropic AAVHSC15 vector. Homology has received Fast Track Designation and orphan drug designation for HMI-102 from the
About Phenylketonuria (PKU)
PKU is a rare inborn error of metabolism caused by a mutation in the PAH gene. PKU results in a loss of function of the enzyme phenylalanine hydroxylase, which is responsible for the metabolism of phenylalanine (Phe), an amino acid obtained exclusively from the diet. If left untreated, toxic levels of Phe can accumulate in the blood and result in progressive and severe neurological impairment. Currently, there are no treatment options for PKU that target the underlying genetic cause of the disease. According to the
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding our expectations surrounding the potential, safety, efficacy, and regulatory and clinical progress of our product candidates; plans and timing surrounding the Phase 1/2 pheNIX trial, including the expansion phase and the potential for conversion to a registrational trial; our position as a leader in the development of genetic medicines; and our participation in upcoming presentations and conferences. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the impact of the COVID-19 pandemic on our business and operations, including our preclinical studies and clinical trials, and on general economic conditions; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; failure to identify additional product candidates and develop or commercialize marketable products; the early stage of our development efforts; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the capabilities of our manufacturing facility; risks relating to the regulatory approval process; interim, topline and preliminary data may change as more patient data become available, and are subject to audit and verification procedures that could result in material changes in the final data; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; failure to obtain
*ALT Grades based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5
**P<0.004; Post-hoc comparison of Cohort 1 vs Cohorts 2&3 using repeated measures MANOVA/regression analysis
Vockley J et al. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genetics in Medicine 2014;16: 188-200.
van Spronsen FJ et al. Key European guidelines for the diagnosis and management of patients with phenylketonuria. Lancet Diabetes Endocrinol 2017; 5: 743–56.
****P<0.05; Post-hoc comparison of Patients 3&6 vs Patients 4&5 using repeated measures MANOVA/regression analysis
Chief Communications Officer
and Corporate Communications
Source: Homology Medicines, Inc.