US FDA grants orphan drug status to Viking Therapeutics' VK0214 to treat X-linked adrenoleukodystrophy

• VK0214 is a novel, orally available thyroid receptor beta (TRß) agonist that selectively regulates the expression of genes believed to be relevant to the manifestation of X-ALD.
• VK0214 is currently being evaluated in preclinical models of X-ALD under a sponsored research agreement with the Kennedy Krieger Institute.  Data to date have demonstrated promising in vivo activity, including significant reductions in plasma very long chain fatty acids (VLCFA), important biochemical markers of disease. 
• "Viking is committed to evaluating the potential of VK0214 for the treatment of X-ALD, a devastating and progressively debilitating disease for which there is no approved therapy.  Our research indicates that VK0214 positively impacts key genes and biomarkers that may affect the onset of X-ALD, which suggests potential therapeutic benefits in this setting," said Brian Lian, Ph.D., chief executive officer of Viking Therapeutics.  "The Orphan Drug designation underscores the importance of new therapies in areas of high unmet medical need, such as X-ALD, and we look forward to the continued advancement of VK0214 for this underserved disease."
• 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 a peroxisomal transporter of VLCFAs, known as ABCD1.  As a result, transporter function is impaired and patients are unable to efficiently metabolize VLCFA.  The resulting accumulation can trigger a rapid, inflammatory demyelination, which leads to cognitive impairment, motor skill deterioration, and even death.  X-ALD is estimated to occur in approximately 1 in 17,000 births. 
• FDA's Orphan Drug Designation programme provides certain incentives for companies developing therapeutics to treat rare diseases or conditions, defined as those affecting less than 200,000 individuals in the US.  A drug candidate and its sponsor must meet several key criteria in order to qualify for, and obtain, orphan drug status.  Once a drug has received orphan drug designation, the developer qualifies for a range of benefits, including federal grants, tax credits, reduction in certain regulatory fees, and the potential for seven years of market exclusivity for the drug following FDA marketing approval.
• VK0214 is a novel, orally available thyroid receptor beta (TRß) agonist that selectively modulates lipoprotein and triglyceride levels in liver tissue.  This mechanism has been demonstrated to affect the expression of the genes that are relevant to the manifestation of X-ALD.  In X-ALD, mutations in the ABCD1 gene lead to the accumulation of very long-chain fatty acids (VLCFAs) which is believed to be a fundamental cause of the disease.
• Research has shown that increasing the expression of the ABCD2 gene can counteract this process and lead to normalization of VLCFA levels.  In preclinical studies, VK0214 has been shown to induce expression of ABCD2 by increasing TRß activity, leading to the belief that it may provide therapeutic benefit to X-ALD patients. 
• 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 a peroxisomal transporter of VLCFAs, known as ABCD1.  As a result, transporter function is impaired and patients are unable to efficiently metabolize VLCFA.  The resulting accumulation can trigger a rapid, inflammatory demyelination, which leads to 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 an alternative VLCFA transporter, known as ABCD2.  Various preclinical models have demonstrated that increased expression of ABCD2 can lead to normalization of VLCFA metabolism.

Us fda grants orphan drug status, viking therapeutics vk0214, treat x linked adrenoleukodystrophy