Synthetic biology company Synlogic has achieved a significant milestone in treating phenylketonuria (PKU), reporting promising Phase 2 results for their novel probiotic-based therapy. The company's innovative approach using engineered strains of Escherichia coli Nissle has demonstrated meaningful clinical benefits, paving the way for Phase 3 trials.
Clinical Trial Results
The Synpheny-1 study, involving 20 PKU patients, evaluated two engineered bacterial strains, SYNB1618 and SYNB1934, designed to break down phenylalanine in the gastrointestinal tract. SYNB1934 emerged as the superior candidate, achieving a mean 34% reduction in fasting plasma phenylalanine levels, compared to a 20% reduction with SYNB1618.
Among responding patients, the results were particularly encouraging, with a 42% reduction in plasma phenylalanine levels. The study defined positive response as a 20% or greater decrease in phenylalanine levels at day seven or 14, which was achieved by 60% of participants.
Treatment Landscape and Unmet Need
PKU, a rare genetic disorder affecting approximately 17,000 people in the US and 150,000 globally, prevents patients from properly metabolizing phenylalanine, an amino acid common in many foods. Without effective treatment, elevated phenylalanine levels can cause severe neurological and neuropsychological complications.
Current treatment options are limited. While BioMarin's Kuvan (sapropterin) and Palynziq (pegvaliase) are available, they are effective in only a minority of patients, with Palynziq associated with significant side effects. Most patients rely heavily on strict dietary restrictions, which can be challenging to maintain and may not provide adequate control of phenylalanine levels.
Safety Profile and Combination Potential
The safety profile of SYNB1934 appears promising, though some adverse events were noted. Three patients discontinued due to gastrointestinal-related issues, one withdrew consent, and another experienced facial flushing attributed to a possible allergic reaction.
Notably, the study included patients already receiving Kuvan treatment, suggesting potential compatibility between the therapies without increased side effects. This finding could expand treatment options for patients requiring combination therapy.
Future Development Plans
Synlogic's CEO Aoife Brennan expressed optimism about SYNB1934's potential as a "transformative treatment" for PKU patients. The company plans to initiate Phase 3 trials in the first half of 2023, anticipating that a single, placebo-controlled registration study might be sufficient for regulatory approval.
This success in PKU treatment development also validates Synlogic's broader biotherapeutic strategy, with additional programs in homocystinuria and enteric hyperoxaluria advancing through clinical development.
