- Arrowhead Pharmaceuticals on Wednesday said it will halt further development of all three of its clinical programs and lay off 30% of its workforce, drastically trimming its footprint in the face of what it termed substantial regulatory delays.
- Earlier this month, the Food and Drug Administration placed a clinical hold on Arrowhead's lead candidate, a RNA-based treatment for hepatitis B, after an unspecified number of animal deaths in a non-clinical toxicology study testing the company's EX1 delivery vehicle.
- Arrowhead said discussions with regulators made it clear that restarting testing on EX1-containing programs, which includes all three clinical candidates, would be delayed significantly. In response, Arrowhead decided to drop the programs and work instead to advance its preclinical pipeline.
Arrowhead stock nose dived in Wednesday morning trading, losing over 60% of its value. Discontinuing the three EX1-containing programs wipes out the California company's entire clinical pipeline, rolling back the clock on the company's development.
Two of the shelved RNAi candidates, ARC-520 and ARC-521, were targeting hepatitis B, while the third (ARC-AAT) targeted alpha-1 antitrypsin deficiency. All made use of EX1, an intravenous delivery vehicle which targets the liver.
Cutting the three programs and laying off 30% of its staff extends Arrowhead's cash runway into 2019, giving the company more time to develop its preclinical candidates. Arrowhead previously expected its cash holdings of just under $44 million (as of June 30) to fund operations for a minimum of 12 months, but will now be able to reduce its R&D and payroll spending.
Yet there is no disguising this setback. Both ARC-520 and ARC-AAT were in Phase 2 testing and Arrowhead had high hopes for both.
Focus will turn now to developing the newer subcutaneous and extra-hepatic delivery systems, which underpin Arrowhead's preclinical pipeline. Amgen recently bought into a collaboration on two RNAi-based cardiovascular therapeutics using those newer systems, putting up $56.5 million upfront.
Arrowhead said the restructuring would not affect its partnership with Amgen.
Alnylam Pharmaceuticals, another company working on developing RNAi therapies, also recently stumbled, stopping development of its experimental drug revusiran in October.