PASADENA, Calif.–(BUSINESS WIRE)–Jul. 17, 2023– Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that it has filed an application for clearance to initiate a Phase 1/2 clinical trial of ARO-DUX4, the company’s investigational RNA interference (RNAi) therapeutic being developed as a potential treatment for patients with facioscapulohumeral muscular dystrophy (FSHD). ARO-DUX4 is the first clinical candidate utilizing Arrowhead’s proprietary Targeted RNAi Molecule (TRiMTM) platform to target disease associated genes in skeletal muscle.
“FSHD is a debilitating disease caused by the aberrant expression of the DUX4 gene in skeletal muscle. ARO-DUX4 engages the RNA interference pathway to selectively inhibit DUX4 expression and is a promising strategy to reverse the downstream myotoxicity of DUX4 and potentially enable stabilization or improvement in muscle function in patients. We believe ARO-DUX4 has the potential to be an impactful new medicine for patients,” said Chris Anzalone, Ph.D., president and CEO of Arrowhead. “As previously communicated, we are in discussions with external parties regarding the most appropriate path for the clinical development and commercialization of ARO-DUX4 with the goal of bringing this promising product candidate to patients in need as expeditiously as possible.”
An application for approval of the clinical trial was submitted to the New Zealand Medicines and Medical Devices Safety Authority for review by the Standing Committee on Therapeutic Trials. Pending clearance, Arrowhead intends to proceed with ARODUX4-1001, a Phase 1/2a dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of ARO-DUX4 in adult patients with FSHD type 1. The study is designed to enroll up to 52 subjects.
ARO-DUX4 is an investigational RNAi therapeutic designed to reduce expression of the gene that encodes the human double homeobox 4 (DUX4) protein as a potential treatment for FSHD. FSHD is an autosomal dominant disease associated with the failure to maintain complete epigenetic suppression of DUX4 expression in differentiated skeletal muscle, leading to overexpression of DUX4, which is myotoxic and can lead to muscle degeneration. Expression of downstream DUX4 associated genes over time leads to muscle fatty infiltration and progressive muscle weakness. As DUX4 overexpression is the cause of muscle pathology in FSHD patients, it is expected that the selective knockdown of DUX4 messenger RNA transcripts using RNA interference will inhibit DUX4 translation, thereby preventing or reversing downstream myotoxicity and allowing muscle repair and partial or complete return of normal muscle function in patients.
Read the full press release here.
What does this mean for patients?
In general, this is great news! The fact that the company filed for permission to start a clinical trial in patients means that they feel that laboratory data on their drug is strong enough to support their case. At the UCLA 360 conference in 2021, Arrowhead shared data (go to 23:20) showing that ARO-DUX4 was able to knock down the expression of DUX4 and prevented loss of body weight in mouse models of FSHD.
More therapies mean more options for treatment. The thinking behind ARO-DUX4 is similar to that of several other companies, including Avidity, Dyne, and miRecule. All of these companies are developing molecules targeting the DUX4 messenger RNA, but there are likely to be differences in the way the molecules are constructed, formulated, and delivered. For example, one drug may be better tolerated in some patients, while another may be better tolerated in a different group. In addition, the companies could market the drug in non-overlapping countries, so if drug A is not available in, say, Japan, drug B may be.
This news is of most immediate relevance for patients in New Zealand, where Arrowhead is seeking to conduct the Phase 1/2 trial. The government has not yet approved the company’s application, so that’s the first milestone to look for. The trial’s main focus is to learn if the drug is safe and doesn’t result in any dangerous or unpleasant side effects. The study will also look at how the body processed the drug. There has never been an FSHD clinical trial in New Zealand, so the challenge for FSHD clinicians, researchers, and patients is to make sure their community is trial ready.
We would love to hear from our members in New Zealand. What are you thoughts?