Employees at Aeglea BioTherapeutics who survived the company’s previous two rounds of layoffs may be left wondering whether it was worth it, as the biotech effectively throws in the towel in response to the latest data from one of its two remaining rare disease candidates.
The company is “exploring strategic alternatives” and letting go of all but 10 employees in response to lackluster interim data from a phase 1/2 trial of pegtarviliase. The novel recombinant human enzyme is designed to lower levels of an amino acid called homocysteine to treat a rare inherited disease called homocystinuria.
While the interim results showed that patients taking the 0.15-mg/kg and 0.45-mg/kg doses experienced lowered total homocysteine levels compared to baseline, the 1.35-mg/kg cohort did not see the same effect. On further analysis, Aeglea identified that patients in this third cohort had developed anti-drug antibodies (ADAs), which reduced the drug’s effectiveness.
"Given the frequency of ADAs seen with other proven effective enzyme therapies, we continue to believe there is a potential for pegtarviliase with further exploration in the clinic,” CEO Jeffrey Goldberg said in the release Wednesday morning. “Additional work on dosing regimens, including dose level, duration and/or frequency, could yield insights into the ability of pegtarviliase to potentially lower homocysteine into a therapeutic range.”
Despite this upbeat assessment, Goldberg still admitted that "unfortunately, we do not believe the data we currently have support immediate dialogue with regulators on a pivotal trial design.”
With the end of the road in sight, Aeglea has tapped Wedbush Securities to help it navigate a path forward, which could include an acquisition, merger, sale of assets or another type of strategic transaction. Chief Business Officer Michael Hanley and Chief Medical Officer Linda Neuman, M.D., will also leave the company.
Aeglea’s stock, which ended Tuesday at an all-time low closing price of 25 cents, fell a further 30% in premarket trading Wednesday to 18 cents.
The latest clinical knock-back proved to be too much for a biotech that had already been clinging on by its fingertips. In January, the enzyme therapy specialist revealed a 15% reduction in its head count—which added to the layoffs made last summer—and the halting of preclinical work. At the time, Aeglea framed the changes as a way to streamline the organization and maximize the value of its two clinical programs, pegtarviliase and pegzilarginase.
Pegzilarginase has also faced a bumpy road toward market, with the FDA hitting Aeglea with a refusal-to-file letter last summer and requesting further evidence of the drug's efficacy. A European approval decision for the treatment of arginase-1 deficiency is due late this year, the biotech confirmed in this morning’s release.