FDA Places Hold on Viking’s Phase 1b Trial of VK0214 in Patients with X-ALD

The U.S. Food and Drug Administration placed a hold on Viking Therapeutics’ phase 1b clinical trial of VK0214 in patients with X-linked adrenoleukodystrophy and requested an additional preclinical study prior to its continuation.

Viking said the request is not due to any findings from ongoing or previously completed studies and it expects to provide the information to the FDA in the second quarter.

The company said it was recently informed that the FDA considers the ongoing trial to be a phase 2 trial rather than a phase 1b.  As a phase 2 trial, a rodent genotoxicity study is required prior to continuation.  Viking had planned to conduct this study prior to phase 2 and will now accelerate its execution.  While a short-term delay is anticipated, the company does not expect the long-term development timeline for VK0214 to be significantly impacted.

“The current request is in keeping with industry guidance for phase 2 studies and is not based on data from previously submitted or ongoing studies, said Brian Lian, CEO of Viking Therapeutics. “We are confident in the overall safety and potential efficacy profile of VK0214 and expect to submit a response with a goal to resume dosing in the study later this year.”

X-linked adrenoleukodystrophy (X-ALD) is a rare and often fatal metabolic disorder characterized by a breakdown in the protective barriers surrounding brain and nerve cells, a process known as demyelination.  The disease, for which there is no approved treatment, is caused by mutations in the gene for a peroxisomal transporter of very-long chain fatty acids (VLCFAs), known as ABCD1. These mutations lead to dysfunction of the adrenoleukodystrophy protein (ALDP), an important peroxisomal transporter, which prevents patients from efficiently metabolizing VLCFAs. The resulting accumulation of VLCFAs, which is believed to contribute to the onset and progression of the disease, can trigger demyelination of nerve cells, resulting in cognitive impairment, motor skill deterioration, and even death. X-ALD is estimated to occur in approximately 1 in 17,000 births.

The thyroid beta receptor is known to regulate expression of a related gene called ABCD2, which encodes a compensatory transporter called the adrenoleukodystrophy related protein (ADLRP). Research in various preclinical disease models has shown that increasing ABCD2 expression can result in normalization of VLCFA levels.

VK0214 is a novel, orally available small molecule TRβ agonist that has been granted orphan drug designation by the FDA for the treatment of X-ALD.  Results from a successful phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy subjects showed that VK0214 demonstrated encouraging safety and tolerability, as well as predictable pharmacokinetics.  In addition, subjects who received VK0214 experienced reductions in low-density lipoprotein cholesterol (LDL-C), triglycerides, and apolipoprotein B following 14 days of treatment.

Author: Rare Daily Staff