Hip Fracture and Muscle Wasting
More than 300,000 people in the U.S. experience hip fractures each year. One year mortality in this group is estimated to range from 20% to 30% and an estimated 50% of patients lose the ability to walk independently. As a result of the loss of mobility, and additional morbidities caused by the hip fracture, 20% of patients will require stays at long-term care facilities. Studies show that following hip fracture, patients experience a severe and rapid decline in lean body mass and bone mineral density (D’Adamo et al., 2014; Fox et al., 2000).
The number of hip fractures is expected to grow in the U.S. as the population ages. Due to required limitations in mobility following hip fracture, patients experience muscle atrophy, or deterioration from lack of use, which impacts the time required for rehabilitation to restore physical function. We believe VK5211’s potential stimulatory effect on lean body mass could result in benefits to patients recovering from hip fracture or other conditions requiring orthopedic intervention, such as hip or knee replacement surgery. Currently, there are no approved therapies to assist in the maintenance or restoration of lean body mass, bone mineral density and restoration of functional performance for these patients.
SARMs and Anabolic Metabolism
Selective androgen receptor modulators, or SARMs, are a class of small molecules designed to elicit the anabolic benefits of androgens, such as testosterone, on tissues such as muscle and bone, without the undesirable effects on prostate and sebaceous glands, by selectively activating androgen receptors in certain tissues. We believe that, based on their robust activity on muscle and bone, SARMs can be used for the potential treatment of a number of diseases or disorders, including muscle wasting, osteoporosis, frailty and hormone deficiency in both men and women in cases where testosterone supplements or anabolic steroid treatments are ineffective or where the side effect profile is inappropriate.
We believe VK5211’s selectivity, limited off-target effects and convenient oral route of administration may make it an attractive potential treatment option for patients recovering from non-elective hip fracture surgery.
In the U.S., the number of patients with dyslipidemia was estimated to be greater than 100 million in 2013. In the U.S., 33.5% of adults, or 71.0 million people, have high LDL cholesterol. NASH is a growing epidemic in the U.S., and is quickly becoming a leading cause of cirrhosis and liver failure. It is estimated that NASH affects 2% to 5% of Americans, or 6.0 to 15.0 million people.
Viking is developing novel drug candidates targeting the thyroid receptor β and the enzyme DGAT-1, for the potential treatment of lipid disorders.
Diabetes is an under-treated disease of epidemic proportion. According to the CDC, as of 2010 an estimated 6.0% of the U.S. population, or roughly 18.8 million people, have been diagnosed with diabetes, and more than 7 million additional are undiagnosed. The International Diabetes Federation estimates that the global prevalence of diabetes will exceed 590 million by 2035. In addition, there are currently approximately 79 million U.S. adults over the age of 20 with pre-diabetes, a condition that raises the risk of developing type 2 diabetes, heart disease and stroke. Pre-diabetes is characterized by higher than normal blood glucose levels, though not high enough to establish a diabetes diagnosis. If left unregulated, abnormally high glucose levels can result in tissue damage involving the nervous system, kidneys, eyes, and circulatory system.
Type 2 diabetes (non-insulin dependent) is the most common form of diabetes, accounting for 90-95% of diagnosed cases. The CDC estimates that approximately 1.7 million patients are diagnosed with type 2 diabetes annually in the U.S. In type 2 diabetes, often both the secretion of insulin from the pancreas and the action of insulin on tissues, such as fat and muscle, are impaired. Patients continue producing insulin, sometimes in excessive amounts, but its secretion and utilization deteriorate over time. In addition, many patients with type 2 diabetes are obese, adversely impacting insulin‘s effectiveness. It is estimated that over half of all patients treated for diabetes fail to achieve recommended blood glucose targets and, according to multiple studies, these patients could benefit significantly from improved glycemic control. The economic burden of diabetes and its associated complications to the U.S. healthcare system was estimated to be $245B in 2012. We believe these factors combine to create a significant, urgent, and growing medical need.
A Global Healthcare Issue
Worldwide prevalence estimated at >300M (IDF 2012)
- U.S. 26M
- E.U. 20M
- India 51M
- Japan 7M
- S. Asia 59M
Projected growth to >590M by 2035
Current U.S.: 25.8M; 8.3% of the population
- 18.8M diagnosed, 7.0M undiagnosed
- 1.9M new diagnoses annually
- 90% of diagnosed (16.9M total, 1.7M annually) are Type 2
Major healthcare burden
- 10% of U.S. healthcare costs directly tied to diabetes
- Approximately $245B in U.S. healthcare costs, 2012
Long-term effects include: Macrovascular complications, renal failure, vision loss, amputation, death
Despite the availability of multiple medications to treat hyperglycemia, either as mono‐ or combination therapy, the majority of patients with type 2 diabetes mellitus (T2DM) fail to meet recommended treatment targets.
Viking’s target market represents a substantial portion of the diabetes population. In the first-line setting, the most commonly prescribed therapy is metformin, a mild gluconeogenesis inhibitor and insulin sensitizer. Despite metformin’s low cost and wide availability, most patients require additional therapies to maintain long-term control of their blood glucose. For example, multiple studies have demonstrated that metformin efficacy wanes for 42% to 52%, or 2.8 million, patients over the course of 2 to 5 years. The annual rate of metformin failure has been reported to be approximately 17%. An additional 15% of type 2 diabetes patients, or 1.6 million, are contraindicated for treatment with metformin, with age, renal impairment, and congestive heart failure the most commonly cited reasons. Further, approximately 5%, or 545,000, patients cannot tolerate initial therapy with metformin and require an alternative. Finally, possibly due to a combination of these issues, an estimated 25% to 30% of patients transition from metformin to an alternative within 12 months of initiating therapy. Underscoring the diabetes community’s dissatisfaction with older agents such as metformin, a recent analysis of prescribing patterns in 255,000 newly-diagnosed type 2 patients found that 35% of those initiating oral therapy did not receive metformin as first-line treatment. This translates into approximately 600,000 newly-diagnosed patient starts per year receiving an oral agent other than metformin.
Inability to prescribe, and loss of responsiveness to, metformin are particularly problematic because alternative first-line therapies such as thiazolidinediones, sulfonylureas, and dipeptidylpeptidase-4 inhibitors, have been associated with increased cardiac risk, hypoglycemia, and pancreatic inflammation, respectively.
In the refractory setting, a challenging subpopulation includes those patients whose disease has progressed to a stage at which adding an injectable medication to their treatment regimen is the only option. Many of these patients are failing combination therapies and ultimately transition to an insulin-only regimen. According to the CDC, patients receiving injectable therapy for type 2 diabetes comprise approximately 28% of the overall population.
To address these significant unmet medical needs, Viking Therapeutics is developing a novel approach to treat hyperglycemia via a mechanism that markedly lowers glucose by inhibiting endogenous glucose production (EGP).
Anemia results from a decrease in red blood cells and is typically experienced by patients with renal complications, cancer patients and HIV/AIDS patients. These patients currently receive recombinant human EPO and other erythropoiesis-stimulating agents, or ESAs. Total worldwide sales of these agents exceeded $7.0 billion in 2012. However, these agents have a number of limitations, including cost of drug manufacturing, cost of treatment, a non-oral route of administration, and potential for immunogenicity, or possibility of inducing an immune response. Furthermore, ESA treatment is associated with an increased risk of adverse cardiovascular complications in patients with kidney disease when used to increase hemoglobin levels above 13.0 g/dL, and may be related to an increase in mortality in cancer patients.
Viking is developing small molecule agonists of the erythropoietin, or EPO, receptor, or EPOR, for the potential treatment of anemia.