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Based on the findings in this early phase, Emerald Health expects to start phase II trials in both MS and scleroderma.
Jim DeMesa, MD, MBA
A phase I trial of EHP-101, an oral formulation of a synthetic new chemical entity (NCE) derived from cannabidiol (CBD) and chemically modified to impact other targets, has been initiated, according to manufacturer Emerald Health Pharmaceuticals.1
The therapy is an oral formulation of VCE-004.8, a cannabinoid derivative which had been shown to alleviate fibrosis in mouse models. It targets and activates the peroxisome proliferator-activated receptor gamma (PPAR-γ) and CB2 receptors, as well as the hypoxia inducible factor (HIF) pathway.
The study will seek to enroll up to 64 healthy volunteers to receive a single increasing dose of EHP-101, between 0.91 mg and 200 mg, or placebo. The primary objective will be to evaluate the safety and tolerability of the therapy, with secondary aims to assess the pharmacokinetic profile, food effects, and the pharmacodynamic effects of the therapy.
Emerald stated that it will also gauge various biomarkers related to the mechanism of action of EHP-101 and its potential for efficacy. It is expected that the therapy will be eventually be assessed in both multiple sclerosis (MS) and scleroderma.
“Our research and development team has demonstrated the unique mechanism of action of EHP-101 in preclinical studies, indicating the potential to treat deadly diseases which currently have no cure,” said Jim DeMesa, MD, MBA, the chief executive officer of Emerald Health. “We believe our novel proprietary oral treatment represents a significant advancement in the treatment of patients with MS and scleroderma.”
The phase I trial is set to be conducted in Australia. It will be a randomized, placebo-controlled, double-blind study completed in 2 parts. Part 1 will include a single-ascending dose phase, where participants will receive the aforementioned doses. Part 2 will include up to 40 eligible subjects to receive EHP-101 or placebo in multiple ascending doses, daily, to be determined based on the results of the first part.
Top-line results of the trial are anticipated to be reported in mid-2019.
DeMesa called the human study initiation “a major accomplishment” and “another important development milestone.” He noted that based on a recent pre-Investigational New Drug application meeting with the FDA, Emerald Health believes the upcoming phase I results will likely be supporting the commencement of phase II studies in both MS and scleroderma.
In mouse studies, the therapy showed a clear effect in the inflammatory and epithelial-mesenchymal transition transcriptomic signatures.2 The investigators noted in the study that these data provide a rationale for further developing the therapy as an orally active agent to alleviate scleroderma and, possibly, they noted, additional fibrotic diseases as well.
In October 2017, the therapy received an Orphan Drug designation from the FDA for its potential to treat systemic scleroderma. DeMesa said at the time that “we are working diligently to address the significant unmet medical need in people suffering from this deadly disease, and this designation furthers our mission to develop impactful cannabinoid-derived medicines to improve clinical outcomes for patients with life-threatening diseases.”
1. Emerald Health Pharmaceuticals Initiates Phase I Clinical Study on its Oral Drug Candidate Derived from Cannabidiol [press release]. San Diego, CA: Emerald Health Pharmaceuticals; Published September 27, 2018. emeraldpharma.life/wp-content/uploads/2018/09/EHP-NR-180927-Clinical-Study-Launch-.pdf. Accessed October 4, 2018.
2. García-Martín A, Garrido-Rodríguez M, Navarrete C. EHP-101, an oral formulation of the cannabidiol aminoquinone VCE-004.8, alleviates bleomycin-induced skin and lung fibrosis. Biochem Pharmacol. 2018;S0006-2952(18):30317-4. doi: 10.1016/j.bcp.2018.07.047.