Third Rock Ventures-backed Allena Pharmaceuticals is about to put investors’ renewed appetite for biotech IPOs to the test. Allena arrives on Wall Street armed with data from two phase 2 flops and a pivotal trial design that has so far failed to win over the FDA.
The Boston-based biotech hopes to parlay this starting position into a $92 million IPO and a push into phase 3. That trial, like the two failed phase 2 studies before it, will test ALLN-177, a crystalline formulation of the oxalate decarboxylase enzyme. The enzyme breaks down oxalate, a molecule that accumulates and causes kidney damage in people with hyperoxaluria.
Allena plans to begin the first of two phase 3 trials in the first quarter of next year, a start date that would set it up to deliver top-line data in the back half of 2019. To do so, Allena needs to add to the $38 million it had in the bank as of the end of June.
Encouraged by Wall Street’s rejuvenated enthusiasm for biotech IPOs, Allena has turned to public investors for the cash. Allena has picked up more battle scars than many of the other biotechs in the IPO class of 2017, though.
The main scars come from two phase 2 trials. The first study assessed ALLN-177 in patients with secondary hyperoxaluria, a form of the condition that stems from overabsorption of oxalate from food. The adaptive design review committee halted the low and mid-dose arms at the first review. And the study was called off altogether once data from 24 patients were available because it was impossible to differentiate between the treatment arms.
Allena’s analysis of why ALLN-177 failed to best placebo focused on variation in how much oxalate participants consumed, the measurement of urinary oxalate and other aspects of the trial’s design.
The trial advanced in parallel to a larger, longer phase 2b study of ALLN-177 that delivered similarly lackluster results. In the 67-patient phase 2b, ALLN-177 failed to reduce urinary oxalate excretion (UOx) by statistically more than placebo, resulting in the study missing its primary endpoint. ALLN-177 did better numerically—but still fell short statistically—in the 18 patients with enteric hyperoxaluria, a rare form of the condition that stems from gastrointestinal problems.
Allena had more success against a secondary endpoint that assessed the reduction in oxalate excretion from baseline to time-weighted average (TWA) across weeks one to four of the trial.
The results prompted Allena to make enteric hyperoxaluria the indication and propose TWA as a possible primary endpoint in its planned phase 3 trial. But, as Allena acknowledges in its IPO filing, it “has limited data on the activity of ALLN-177 in the target population” for the planned phase 3 program.
Allena also acknowledged that there is significant natural intra- and interpatient variation in UOx—its primary endpoint for the phase 2 trials—and the techniques used to collect data against the endpoint. The trial design sought to mitigate the risk of variability affecting the results, but Allena said it cannot guarantee that all the data reported in its clinical trials “accurately reflect the actual biochemical responses experienced by patients.”
The final complication for Allena relates to its discussions with the FDA. Allena has proposed some primary endpoints to the FDA. But, while the FDA “may be willing to accept a substantial change in 24 hour UOx excretion,” Allena has yet to make a wholly convincing case to the agency.
“The FDA has also advised us that we have not yet provided sufficient data regarding the magnitude of effect on UOx excretion necessary to support its use as a primary endpoint for these clinical trials,” Allena wrote in its S-1. “If we are unable to reach consensus with the FDA on the magnitude of UOx reduction significant enough to predict clinical benefit, we may be required to demonstrate effectiveness by showing an effect on stone formation directly, or conduct one or more additional clinical trials to demonstrate this effect, prior to the submission of a BLA for ALLN-177.”