Aeglea's search for signs of efficacy in phase 3 rare disease data impresses investors, sending stock up 30%

Aeglea BioTherapeutics’ bid to rehabilitate the battered reputation of its rare disease drug pegzilarginase has made early progress. Investors responded favorably to the presentation of additional phase 3 data, sending the stock up around 30% in light of evidence the enzyme may act on clinical outcomes. 

Late last year, Aeglea presented top-line data on 32 patients with arginase-1 deficiency, a rare genetic disorder that can cause seizures, spasticity and intellectual disability in untreated children. The readout showed the recombinant human enzyme pegzilarginase normalized plasma arginine levels, causing the study to hit its primary endpoint, but investors zeroed on missed secondaries and sank the stock.

Now, Aeglea has presented additional results from the study that have partly reinvigorated the interest of some investors. The centerpiece of the update is a patient-level analysis of a subgroup of patients. 

Aeglea limited its analysis to participants in the 32-subject trial that scored in the top three ranks on a motor function classification system, thereby excluding patients with more severe mobility issues. At worst, children in the top three ranks walk using a hand-held mobility device in most indoor settings and can climb stairs holding onto a railing with supervision or assistance.

In that subgroup, 65% participants who received pegzilarginase met the pre-specified response criteria for at least one of the studied mobility measures, compared to 44% of their peers on placebo. Almost half of the participants on pegzilarginase met the criteria for at least two measures, compared to none of their counterparts on placebo.

The three mobility measures used in the trial were the two-minute walk test and two parts of a motor function measure, which look at standing and walking, running and jumping. Aeglea measured clinical response in terms of whether participants met the criteria for at least one of the measures. 

In its top-line readout, Aeglea pointed to a positive trend on the walking, running and jumping endpoint, but the failure to drive a statistically significant improvement on the clinical measures was the key takeaway for investors. The latest update adds information about the standing endpoint. In the original analysis of the measure, a missed assessment was improperly scored as 0 rather than not assessed. Aeglea corrected the error in a post hoc analysis, but the p-value still only came in at 0.0896.

The updates were enough to cause a bounce in Aeglea’s share price. The stock dropped more than 30% after the top-line data and continued to slide over the following months to languish at below $2.50 when the markets closed Monday. The new data moved shares up above $3 before dropping to $2.70 by 9:40am ET, still well below the $6 they commanded before the top-line readout but a notable upswing for a stock that has largely headed in one direction this year.