Synlogic Announces Positive Top-Line Phase 2 Data for Phenylketonuria (PKU); SYNB1934 Advances to Phase 3
Positive results include clinically meaningful Phe reductions, with a 60% response rate and 42% reduction in plasma Phe among responders across the study population
Consistent, positive measures of activity across all assessed endpoints
Company confirms SYNB1934 as candidate for Phase 3 initiation expected in H1 2023
Synlogic to Host Webcast Today at
- The Phase 2 study enrolled 20 patients with PKU; 11 were enrolled in the SYNB1618 arm and 9 patients were enrolled in the SYNB1934 arm.
- Both strains demonstrated clinically meaningful reductions in fasting plasma Phe. On an “all comers” basis, the day 14 mean change from baseline in fasting plasma Phe was -20% for SYNB1618 and -34% for SYNB1934.
- Results were consistent and positive across all measured indicators of activity for both drug candidates, including plasma D5-Phe, plasma D5-TCA and urinary D5-HA, with numerically greater changes observed for SYNB1934, consistent with previously shared results in healthy volunteers.
- Results from patients who were already taking sapropterin (Kuvan®) at baseline, and then received SYNB1618 and SYNB1934, were consistent with the overall efficacy profile, demonstrating the potential for adjunctive use.
- All adverse events were mild or moderate in severity and were predominantly gastrointestinal (GI) in nature. There were no serious adverse events (SAEs).
“PKU continues to be a very challenging disease for patients, with many in need of new treatment options,” said Dr.
“We are tremendously excited to share these top-line data from our Phase 2 study showing consistent positive results across all endpoints in patients with PKU. In particular, the robust plasma Phe reduction demonstrated by SYNB1934 indicates that it has potential to be a transformative treatment for patients with PKU,” said
The Phase 2 Synpheny-1 Study
The Phase 2 Synpheny-1 study is a Phase 2, open-label, 28-day study to assess safety, tolerability and efficacy of SYNB1618 and SYNB1934 in patients with PKU. The primary endpoint is the change in area under the curve (AUC) of plasma levels of labeled D5-phenylalanine (D5-Phe) after a meal challenge before and after the treatment period, a specific indicator of each drug candidate’s ability to consume Phe as intended. The study included a dose-ramp regimen over 15 days of treatment, with days 7 through 14 at the constant dose of 1x1012 live cells. Additional endpoints include change from baseline in fasting levels of plasma Phe, and incidence of treatment-emergent adverse events (TEAEs), as well as the levels of additional strain-specific metabolites plasma D5-TCA and urinary D5-HA. Dietary intake of Phe was carefully managed during the study to match patients’ usual protein and Phe intake.
Synpheny-1 enrolled 20 adults with PKU who had a Phe level above 600 μmol/L at screening despite treatment with diet and/or sapropterin. Eleven patients were enrolled in the SYNB1618 arm and 9 were enrolled in the SYNB1934 arm. Ten patients have completed the SYNB1618 arm and 5 patients have completed Arm 2 with SYNB1934.
Results included achieving a reduction in plasma levels of labeled D5-phenylalanine (D5-Phe), and in fasting plasma Phe levels from baseline for both strains. On an “all comers” basis among patients who completed dosing, the day 14 mean change from baseline in fasting plasma Phe was -20% for SYNB1618 and -34% for SYNB1934. Results included data from patients who were already taking sapropterin (Kuvan®) at baseline, and then received SYNB1618 and SYNB1934. In these patients, results were consistent with the overall efficacy profile, demonstrating the potential for adjunctive use.
Response was defined as >20% reduction in Phe at either day 7 or day 14. Overall, 60% of patients enrolled who completed dosing in the study met these criteria (six of the ten patients dosed with SYNB1618 and three of the five that have completed dosing with SYNB1934 met this criterion). Phe reduction for those responders in aggregate averaged -42%. The ranges for Phe reduction among responders by strain were -20% to -61% and -29% to -80% for SYNB1618 and SYNB1934, respectively.
Adverse events were all mild to moderate and predominantly GI in nature. Results were similar across SYNB1618 and SYNB1934. There were no serious adverse events (SAEs). Across the study, three patients discontinued due to GI-related adverse events, one withdrew consent, and one patient withdrew following an adverse event of facial flushing which was attributed to a possible allergic reaction.
Full data from the Phase 2 study are expected to be presented at upcoming medical meetings and submitted to peer-reviewed medical journals.
Based on data obtained across the PKU program,
- Share data from the Phase 1 trial in healthy volunteers for SYNB1353 for homocystinuria (HCU) in H2 2022
- Share proof of concept data for SYNB8802 for enteric hyperoxaluria (EH) in H2 2022
Conference Call & Webcast Information
Synlogic will host a conference call and live webcast at 8:30 a.m. ET today, October 18, 2022. To access the webcast, please register here. To access the call by phone from the
Synlogic is a clinical-stage biotechnology company developing medicines through its proprietary approach to synthetic biology. Synlogic’s pipeline includes its lead program in phenylketonuria (PKU), which has demonstrated proof of concept with plans to start a pivotal, Phase 3 study in the first half of 2023, and additional novel drug candidates designed to treat homocystinuria (HCU), enteric hyperoxaluria and gout. The rapid advancement of these potential biotherapeutics, called Synthetic Biotics, has been enabled by Synlogic’s reproducible, target-specific drug design. Synlogic uses programmable, precision genetic engineering of well-characterized probiotics to exert localized activity for therapeutic benefit, with a focus on metabolic and immunological diseases. In addition to its clinical programs, Synlogic has a research collaboration with Roche on the discovery of a novel Synthetic Biotic for the treatment of inflammatory bowel disease or IBD.
About SYNB1934 and SYNB1618
SYNB1934 and SYNB1618 are orally administered, non-systemically absorbed drug candidates being studied as potential treatments for phenylketonuria (PKU), a genetic disease caused by potentially neurotoxic levels of the amino acid phenylalanine (Phe). Treatment options for PKU are currently limited due to efficacy and safety, and many of those who are treated are in need of additional Phe-lowering.
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Source: Synlogic, Inc.