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Mid-stage Data on Allena's Hyperoxaluria Drug Fuel Optimism Ahead of Pivotal Readout

Ahead of the pivotal data of its lead experimental drug for hyperoxaluria, Allena Pharmaceuticals revealed interim data from a small mid-stage study on Wednesday, that signaled the drug confers benefits in certain patients with advanced chronic kidney disease (CKD) that are at risk of systemic oxalosis, a potentially life-threatening condition.

Hyperoxaluria occurs due to high levels of oxalate — a natural chemical — in urine. Oxalosis occurs after the kidneys fail in individuals who have primary and intestinal causes of hyperoxaluria, and excess oxalate builds up in the blood. This can lead to oxalate deposits in blood vessels, bones and body organs, according to the Mayo Clinic.

The company disclosed data from study 206 involving seven patients with progression of primary hyperoxaluria (PH) — a rare condition characterized by recurrent kidney and bladder stones — or enteric hyperoxaluria (EH), which predisposes patients to excess oxalate absorption due to an underlying gastrointestinal disorder.

In the single-arm trial, designed to enroll between 15 and 20 patients, who were orally administered 7,500 units of reloxaliase for 12 consecutive weeks. The primary endpoints of the trial are changing from baseline in 24-hour urine oxalate (UOx) and plasma oxalate (POx) secretions (UOx was collected for patients who are not on dialysis).

All four EH patients experienced an average reduction of 40% in POx compared to baseline. The two patients not on dialysis also experienced reductions in UOx of 29% and 42%, respectively. Three patients with PH type 2 or PH type 3 with preserved renal function were treated — one patient had a >20% mean reduction in UOx excretion, while the other two patients did not show a response to reloxaliase, Allena $ALNA said on Tuesday.

“Overall, we see the data as encouraging for the EH population (including those with chronic kidney disease), but murkier for the PH population,” Credit Suisse analysts said. “While this is a small setback, we see Allena’s plan to narrow its further evaluation of reloxaliase in PH to patients with compromised renal function and where the drug’s GI mechanism of action may play a more important role as sensible. We also note that PH is a much smaller market opportunity in general, given that there are only ~5,000 patients in the US (vs. ~250,000 in the US with EH).”

The data provides optimism ahead of the Phase III readout, analysts said. Topline data from the late-stage study is expected in the second half of the year — and an additional study 206 data is also incoming.

“Importantly, two stage 3 pts met Ph3 inclusion criteria, providing +ve read-through to ongoing Ph3’s given similar endpoint, study length, dose strength and dosing frequency. Mean 35% reduction in UOx exceeded the target 20% in Ph3’s,” Jefferies analysts wrote.

Ahead of the late-stage readout, Baird analysts had also underscored the importance of a clean safety profile after dosing frequency was changed from 3 times daily to 5 times daily.  “While the current results only include 4 patients with EH, the absence of treatment-related serious adverse events for relox in the basket trial gives us further confidence for the enzyme’s safety profile in URIROX-1/2, particularly as these 4 EH patients were substantially severe cases…In short, today’s basket data, while early, give us incremental optimism for relox’s tolerability in pivotal studies in EH.”

Reloxaliase is a crystalline formulation of the enzyme oxalate decarboxylase, which degrades oxalate within the gastrointestinal tract, thereby limiting systemic absorption of oxalate into the bloodstream. This reduces the burden on the kidney to filter and excrete oxalate in the urine and, in turn, diminishes the risk of kidney stones and other serious renal disorders.


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