Arrowhead and Janssen Launch Phase 2b Trial of RNAi-Based Triple Combination Therapy for Functional Cure of Hepatitis B

News on August 31, 2019 /BioValleyBIOON/ -- Arrowhead Pharmaceuticals, an RNAi therapeutics company, is currently collaborating with Johnson & Johnson to develop RNAi drugs with the potential to functionally cure hepatitis B virus (HBV) infection. Recently, the company announced that Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, has begun administering different combination regimens to patients in its Phase IIb study (REEF-1), including the RNAi drug JNJ-3989 (formerly known as ARO-HBV) and/or JNJ-6379, along with a nucleos(t)ide analogue (NA). With the initiation of this study, Arrowhead received a $25 million milestone payment from Janssen.

Johnson & Johnson and Arrowhead Pharmaceuticals entered into a licensing and collaboration agreement in October 2018 to develop and commercialize JNJ-3989, a liver-targeted, subcutaneously administered antiviral agent designed to treat hepatitis B virus (HBV) infection via an RNA interference (RNAi) mechanism. Currently, JNJ-3989 is being developed as a potential curative therapy for individuals with HBV infection. JNJ-3989 silences all HBV gene products and intervenes upstream of the reverse transcription process targeted by standard-of-care nucleotide and nucleoside analogs, thereby enabling the body’s natural immune defenses to clear the virus and achieve a functional cure.

JNJ-6379 is an orally administered capsid assembly modulator (CAM) that inhibits normal capsid assembly during HBV replication.

Dr. Christopher Anzalone, President and Chief Executive Officer of Arrowhead Pharmaceuticals, stated, “There is an urgent need for new therapies for patients with chronic hepatitis B infection that can improve rates of functional cure. We are pleased that JNJ-3989 is one of the agents being investigated in Janssen’s REEF-1 Phase IIb study of a triple-drug combination.”

REEL-1 (NCT03982186) is a multicenter, double-blind, active-controlled, randomized Phase IIb study designed to investigate the efficacy and safety of different combination regimens (including JNJ-3989, JNJ-6379, NA, and/or placebo) in patients with chronic hepatitis B virus infection. The study plans to enroll 450 patients, who will be randomized to receive treatment for up to 48 weeks.

Major Therapeutic Targets for HBV (Image source: Literature - DOI:10.1080/13543784.2017.1333105)

Chronic hepatitis B (CHB) is a life-threatening chronic viral liver infection that can lead to cirrhosis (scarring of liver tissue) after long-term chronic infection, andLiver CancerThe World Health Organization (WHO) states that hepatitis B is a global public health issue, affecting 292 million people worldwide. Although preventive vaccines are available, the cure rate for infected individuals remains low, and most patients will require lifelong treatment.

Currently, hepatitis B drugs available on the market can only suppress viral replication but cannot eliminate the virus. Drugs based on RNA interference (RNAi) and antisense RNA technology can specifically seek out, bind to, and degrade HBV RNA transcripts, silence all HBV gene products, prevent the production of viral proteins, and intervene upstream of the reverse transcription process targeted by current standard-of-care nucleotide and nucleoside analogs. The knockdown of viral proteins is expected to restore the body's natural immune defense system's response to HBV, thereby clearing the virus and achieving a functional cure. Such drugs hold promise for revolutionizing the treatment of hepatitis B.

Currently, multiple pharmaceutical companies are leveraging RNA interference (RNAi) and antisense RNA technologies to develop therapeutics for chronic hepatitis B. In addition to Johnson & Johnson/Arrowhead Pharmaceuticals (JNJ-3989, formerly known as ARO-HBV), these include Ionis/GlaxoSmithKline(antisense RNA drugs), Vir/Alnylam (VIR-2218), Arbutus Biopharma (GalNAc-RNAi drug AB-729), Dicerna Pharmaceuticals (DCR-HBVS), etc.

Just recently,GlaxoSmithKlineExercising its option, the company licensed two antisense RNA drugs for the treatment of chronic hepatitis B virus (HBV) infection from Ionis Pharmaceuticals: IONIS-HBVRx, an antisense drug, and IONIS-HBV-LRx, a ligand-conjugated antisense (LICA) drug. The latter is the first anti-infective agent developed using LICA technology, which aims to enhance drug delivery to target tissues, thereby improving efficacy. Both drugs are designed to reduce the production of viral proteins associated with HBV infection and replication, including hepatitis B surface antigen (HBsAg), which is present in both acute and chronic infections and is associated with poor patient prognosis. (Bioon.com)

Original Source:Arrowhead Collaborator Janssen Begins REEF-1 Phase 2b Combination Study in Patients with Chronic Hepatitis B Infection