ARWR - Arrowhead stock dips ~15% amid phase 2 data for liver disease drug fazirsiran

Takeda ( NYSE: TAK ) and Arrowhead Pharmaceuticals ( NASDAQ: ARWR ) reported data from a phase 2 trial of fazirsiran (TAK-999/ARO-AAT) to treat liver disease associated with alpha-1 antitrypsin deficiency (AATD-LD).

Alpha-1 antitrypsin protein (AAT) is made in the liver cells and sent to the lungs where it helps protect the lungs from damage. Having low levels of AAT may cause damage to lungs and a build-up of abnormal AAT may cause liver damage.

The study, dubbed SEQUOIA, included 42 patients with AATD-LD. The patients were enrolled in three groups to receive the investigational RNA interference (RNAi) therapy fazirsiran at doses of 25 mg (n=9), 100 mg (n=8), 200 mg (n=9), or matching placebo (n=14).

The companies said patients receiving fazirsiran who had baseline fibrosis (n=16) showed a dose dependent mean reduction in serum mutant alpha-1 antitrypsin protein (Z-AAT) concentration at week 48 of 74%, 89%, and 94%, respectively.

All three doses led to a reduction in total liver Z-AAT with a median reduction of 94% at the postbaseline liver biopsy visit, the companies added.

The companies noted that 50% of patients achieved an improvement in fibrosis of at least one point by METAVIR stage.

Meanwhile, by week 48 patients receiving placebo who had baseline fibrosis (n=9) saw no meaningful changes from baseline in serum Z-AAT, a 26% increase in liver Z-AAT, no meaningful change in PAS-D globule burden, the companies noted.

No placebo patients experienced an improvement in portal inflammation while 44% experienced worsening, and 22% of placebo patients experienced worsening while 38% experienced an improvement in fibrosis at the postbaseline liver biopsy visit, according to the companies.

The companies said that this finding highlights the known variability on histologic fibrosis assessment. With a larger sample size, like in a planned phase 3 study, the rate of improvement in patients receiving placebo may more closely link to results from natural history studies of untreated patients with AATD-LD.

Fazirsiran was well tolerated with treatment emergent adverse events were well balanced between fazirsiran and placebo groups, according to the companies.

This month Takeda plans to start a phase 3 trial evaluating fazirsiran versus placebo to treat alpha-1 antitrypsin deficiency–associated liver disease with METAVIR stage F2 to F4 fibrosis.

ARWR -18.41% to $30.50 premarket Jan. 9

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