FDA Lifts Clinical Hold on Viking’s X-ALD Trial

The U.S. Food and Drug Administration has lifted its clinical hold on Viking Therapeutics’ trial of VK0214 in patients with X-linked adrenoleukodystrophy.

The company said it expects to resume study enrollment in the coming weeks.

The FDA lifted the clinical hold following its review of results from an in vivo genotoxicity study that it had requested due to the study being conducted with multiple doses in patients. Viking had planned to conduct this study prior to phase 2 but accelerated its execution based on FDA’s request.

The study was completed and the results submitted to the agency in the second quarter. The results showed no evidence of genotoxicity following exposure to VK0214. The company does not believe that the long-term development timeline for VK0214 has been significantly impacted by the temporary clinical hold.

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 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.

VK0214 is a novel, orally available small molecule thyroid hormone beta receptor (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.

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 very long chain fatty acids levels.

The phase 1b study of VK0214 is designed to enroll patients with the adrenomyeloneuropathy (AMN) form of X-ALD. AMN is the most common form of X-ALD, affecting approximately half of patients. The trial is a multi-center, randomized, double-blind, placebo-controlled study in adult male patients with AMN. The primary objectives of the study are to evaluate the safety and tolerability of VK0214 administered once-daily over a 28-day dosing period. The study also includes an exploratory assessment of the impact of VK0214 on plasma levels of very long chain fatty acids, as well as an evaluation of the pharmacokinetics of VK0214 in these patients.

“We look forward to resuming study activities and working to complete patient enrollment as quickly as possible,” said Brian Lian, CEO of Viking Therapeutics. “We are confident in the overall safety and potential efficacy profile of VK0214 to date, and are eager to continue its advancement as a potential disease modifying treatment for patients with X-ALD.”

Author: Rare Daily Staff