Viking Therapeutics Phase 2 trial results expected mid-year
Viking Therapeutics, Inc. ( VKTX) is a biopharmaceutical company developing treatments for metabolic and endocrine disorders. The company’s lead compounds include:
1) VK5211, which is being developed for acute rehabilitation following non-elective hip fracture surgery.
– Viking anticipates data from the ongoing Phase 2 study of VK5211 in hip fracture in mid-2017.
2) VK2809, which is being developed for the treatment of hypercholesterolemia and fatty liver disease, with work set to begin in the second half of 2017 in glycogen storage disease type Ia (GSD Ia).
– Viking anticipates data from the ongoing Phase 2 study of VK2809 in fatty liver disease later in 2017, and to initiate a human proof-of-concept study in GSD Ia in the second half of 2017.
3) VK0214, which is being developed for the treatment of X-linked adrenoleukodystrophy (X-ALD).
– A long-term study in an in vivo model of X-ALD is currently ongoing, with results expected in the second quarter of 2017.
Viking’s most advanced drug candidate is VK5211, a third-generation non-steroidal Selective Androgen Receptor Modulator (SARM) that is being developed for maintenance or improvement of lean body mass (LBM), bone mineral density (BMD), and function in patients recovering from non-elective hip fracture surgery. Hip fracture is associated with a number of morbidities, the majority of which are the result of deleterious changes in body composition following the injury. In the first year after a hip fracture, fat mass increases by up to 7% ( Karlsson et al., 1996) while lean mass decreases by up to 11% ( Fox et al., 2000). This is in comparison to healthy older females who lose approximately 1% of lean mass per year and gain approximately 1.7% in fat mass ( Karlsson et al., 2000).
SARMs are a group of compounds designed to act as androgen receptor (AR) agonists in muscle and bone while being partial agonists in other areas of the body (e.g., prostate). The most prominent androgen, testosterone, stimulates the growth of muscle and bone (anabolic effects) as well as the prostate and sebaceous glands (androgenic effects), and is considered a non-tissue-selective androgen.
While androgens inhibit fat accumulation and increase skeletal muscle growth, two properties that make them ideal therapeutic candidates for restoring or preserving body composition following hip fracture, the use of testosterone therapy has a number of side effects including prostate growth ( Meikle et al., 1997) and polycythemia ( Snyder et al., 2000) in men and acne, alopecia, and hirsutism in women ( Phillips et al., 1997) that precludes its use in a large number of patients. Thus, what would be most beneficial would be a product that provided the anabolic effects of androgen therapy with limited androgenic effects.
VK5211 was originally developed by Ligand Pharmaceuticals, Inc. (LGND) and was previously tested in preclinical models and early stage clinical trials. Two Phase 1 clinical trials showed the drug to be safe and well-tolerated at all doses following daily oral administration for up to 21 days. The drug selectively activates AR in muscle and bone, stimulating muscle and bone growth, while avoiding undesirable side effects, such as unwanted hair growth, acne, or prostate growth.
To examine the safety and physiological changes that occur after 13 weeks of VK5211 dosing, cynomolgus monkeys were orally administered VK5211 once daily at 0, 0.6, 3, 15, or 75 mg/kg. The following figure shows a significant increase in body weight in both male and female monkeys during the 13 weeks of dosing. The fact that the results were seen in females is important, as the majority of hip fractures occur in females.