Aeglea BioTherapeutics found itself in an unusual position going into the readout from its pivotal rare disease clinical trial. With Aeglea expected to meet its primary endpoint, investors were focused on whether it could show clinical improvement of a secondary measure—and were swift to punish the stock when it fell short of expectations.
The clinical trial randomized 32 patients with arginase-1 deficiency, a rare genetic disorder that can cause seizures, spasticity and intellectual disability in untreated children, to receive weekly infusions of pegzilarginase or placebo for 24 weeks. Pegzilarginase is a recombinant human enzyme designed to lower levels of arginine and thereby improve outcomes in patients who are unable to break down the amino acid.
Aeglea has emerged from the study armed with evidence that pegzilarginase lowers arginine levels but with question marks over what that means for the health of patients. The good news for Aeglea is that the trial linked pegzilarginase to an 80% reduction in mean plasma arginine. More than 90% of patients on pegzilarginase had normal plasma arginine levels.
Beyond that, the situation is less clear-cut. Aeglea hailed the clinical trial as linking pegzilarginase to a positive trend in a measure of mobility, including the ability to walk, run and jump. Mobility scores improved in the treatment arm and worsened in the placebo group, but the difference fell short of statistical significance and, consequently, short of investor expectations.
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With a positive trend on a two-minute walk test also falling short of statistical significance, shares in Aeglea fell almost 30% in premarket trading, slumping to below $5 despite the principal investigator putting a positive slant on the data.
“Clinicians recognize the importance of effective arginine control, and I am delighted that the PEACE pivotal trial demonstrated that pegzilarginase lowered plasma arginine to normal levels and also showed a positive trend in an important mobility assessment of clinical benefit,” Mount Sinai Hospital’s George Diaz, M.D., Ph.D., said in a statement.
The question now is whether a statistical win against a biomarker and positive trends on two clinical measures is enough to get pegzilarginase to market. Aeglea is betting that it will be, outlining plans to file for FDA approval in the first half of next year and work with its European partner Immedica Pharma to submit applications outside of the U.S.