Synlogic reported Tuesday that it will end development of SYNB1020 after the experimental drug produced disappointing top-line results in a Phase Ib/IIa study in patients with cirrhosis and elevated blood ammonia. Shares in the drugmaker plunged as much as 28% on the news.
An initial open-label phase of the trial involved six patients with cirrhosis and a Model for End-Stage Liver Disease (MELD) score of less than 12 who received the oral therapy for six days. The second part of the trial included a total of 17 patients with cirrhosis and hyperammonaemia who were randomly assigned to treatment with SYNB1020 or placebo orally for six days. The primary endpoint was safety and tolerability, while the study also evaluated the effect of SYNB1020 on levels of plasma ammonia, as well as other exploratory endpoints, including levels of IL-6, TNF-alpha and endotoxin, and psychometric hepatic encephalopathy scores (PHES).
According to Synlogic, SYNB1020 was well tolerated in the trial. However, while plasma and urinary nitrate levels rose in patients treated with SYNB1020, "indicating that the strain was active," the company said there was "no evidence" of blood ammonia lowering or changes in other exploratory endpoints relative to placebo.
CEO Aoife Brennan said "we are disappointed that results…did not demonstrate an activity profile in ammonia lowering that warranted continued development of the programme." Synlogic noted that detailed results from the study will be unveiled at a research conference.
SYNB1020 had previously been granted a fast-track designation by the FDA for the treatment of hyperammonaemia in urea cycle disorders. "Moving forward, we will focus our resources on advancement of SYNB1618 for the treatment of phenylketonuria, SYNB1891 for the treatment of solid tumours and several new programmes in early development," stated Brennan.
Last month, Synlogic announced top-line data from a Phase I/IIa study demonstrating significant biomarker activity at a well-tolerated dose of a liquid formulation of SYNB1618 in patients with phenylketonuria. The company said it plans to initiate a bridging study with a new oral solid formulation of SYNB1618 in the third quarter. The therapy has already received orphan drug and fast-track designations from the FDA for this indication.
Meanwhile, Synlogic inked a deal with Roche in May to develop SYNB1891, a dual innate immune activator engineered to express a STING agonist, in combination with the latter's PD-L1 inhibitor Tecentriq (atezolizumab) for use in patients with advanced solid tumours.
To read more Top Story articles, click here.