Arrowhead doses first RNAi hepatitis B 'functional cure' PhIIa patient

Arrowhead CEO Chris Anzalone

Arrowhead ($ARWR), fresh off a $120 million public offering in February, is paving the way for what it has called a "functional cure" for hepatitis B, beginning dosing in a Phase IIa trial for its RNAi drug designed to deliver the genetic material to the nucleus using a polymer-based conjugate.

Late last year, the candidate, called ARC-520, was shown to substantially reduce the viral DNA and antigens associated with hep B for over two months. And an "immunological flare" demonstrated in a primate study resulted in an increase in serum alanine transaminase after four weeks, according to the company, which could lead to a "functional cure," which is defined by the antigen conversion.

In the mid-stage trial, Arrowhead will enroll up to 16 patients with chronic hep B for intravenous injection of ARC-520 in combination with the oral drug entecavir. The goal is "to evaluate the depth and duration of hepatitis B surface antigen decline, among other measures, in response to a single dose of ARC-520," according to Arrowhead. It will take place at Queen Mary Hospital and Prince of Wales Hospital in Hong Kong.

ARC-520, like Arrowhead's other candidates, makes use of the company's delivery system designed over the last decade to overcome the vast challenges associated with RNAi delivery. The polymer-based platform stands apart from other RNA delivery platforms in its ability to induce endosomal escape, or release of the drug, Arrowhead CEO Christopher Anzalone told FierceDrugDelivery in October last year. The method uses a "masking" and "unmasking" process, which allows the RNA to enter the cell unharmed and then do its job once it's in there.

With RNA drugs, the challenges have mostly to do with protecting the genetic material enough to allow it to survive on its way to cells, but also make it available enough to be effective once it gets there.

"This is a significant milestone for the ARC-520 program and has broad implications for the development of additional RNAi therapeutics using the Dynamic Polyconjugate, or DPC, delivery system," Anzalone said in a statement. "We took an important step toward clinical validation of the DPC system when the Phase I completed and data indicated that ARC-520 was generally safe and well tolerated across all dose levels studied."

Arrowhead isn't the only RNA player on the field: Alnylam ($ALNY) is considered the leader of the pack with several candidates in clinical trials and a hefty deal with Sanofi ($SNY) to boot, and Arcturus also has a stake in the relatively new technology.

"Our next step will be confirmation ARC-520 induces deep and durable target gene knockdown in humans," Anzalone continued. "We are confident that the Phase IIa will rapidly provide us with the data necessary to make that assessment as we anticipate patient enrollment and dosing may be complete in the second quarter of this year."

- here's the release

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