New drug Vida-5 for treating chronic kidney disease progression

DESCRIPTION (provided by applicant): Twenty-six million people in America have chronic kidney disease (CKD). Anemia, cardiovascular diseases, secondary hyperparathyroidism, renal osteodystrophy and other complications are common in CKD. Current treatmentsincluding ACE inhibitors for CKD patients mainly focus on managing symptoms and disease complications. Despite the various treatments available, the five-year survival rate is ~33% and the mortality risk increases with kidney disease progression and secondary hyperparathyroidism. Vitamin D receptor modulators (VDRMs) have been shown to reduce proteinuria/albuminuria in CKD patients and also provide survival benefits for CKD patients. Despite encouraging data on VDRM's potential renal and survival benefits for the CKD patients, currently in the CKD field VDRM is only indicated for managing secondary hyperparathyroidism (with elevated PTH). Hypercalcemic toxicity that interferes with calcium homeostasis and detriments body functions is the limiting factor to expanded use of on-market VDRMs. Therefore, a novel VDRM which retains the efficacy without the toxicity shared by current VDRMs would have significant clinical benefit. An ideal VDRM should be with little or no hypercalcemic toxicity in the efficacious dose range that could reduce PTH and slow kidney disease progression. Vidasym has taken a unique drug discovery/development approach to discover novel VDRMs that are highly differentiated from existing VDRMs. Vidasym's Vida-5 has no detectable hypercalcemic toxicity in the dose range that suppresses PTH to the normal level (vs. other VDRMs with overlapping dose ranges for efficacy and toxicity). With Vida-5's superior safety and efficacy profiles established, the next step is to determine the feasibility of using Vida-5 to treat kidney disease progression and also its long-term side effect potential in animal studies. The specific aims of this Phase I study are: (1) to conduct an animal study to show the synergistic effect of Vida-5 and an ACE inhibitor on reducing biomarkers (such as serum creatinine and proteinuira) indicative of kidney disease progression; (2) to conduct a toxicity animal study to prepare Vida-5 for Phase II studies. Once this phase I study is completed the data will allow the advancement ofVida-5 into Phase II IND-enabling studies including Vida-5 synthesis scale-up, process development and pharmacokinetics, metabolism, safety and toxicology. The completion of Phase II studies will allow Vida-5 to enter human clinical trials. Vidasym plans to develop Vida-5 into a reimbursable prescription new drug to treat kidney disease progression. Once developed, such a drug will not only reduce the mortality rate of CKD, but also reduce the need for dialysis. Current VDRMs for secondary hyperparathyroidism alone achieve US 1+ billion in annual sales in 2009. Zemplar and Hectorol dominate the US dialysis market (gt80%) due to their slightly less hypercalcemic toxic profile (~2-4 fold less toxic than generic Calcijex, the endogenous hormone calcitriol,). Anovel VDRM such as Vida-5 for treating kidney disease progression could easily achieve an annual US sales at 1+ billion. PUBLIC HEALTH RELEVANCE: Vidasym's phase I SBIR study will determine the feasibility of using Vida-5 to treat chronic kidney disease (CKD) progression. Globally gt 350 million individuals have CKD and this number is projected to increase to gt550 million by 2025. Although various modalities and substances are available for CKD, the mortality rate for CKD patients remains high (~33%) and the number of dialysis CKD patients keeps increasing. There is an urgent medical need for the development of an effective and novel resuscitation approach for the treatment of CKD. Limitations of current therapy demonstrate that a new treatment approach such as Vida-5 to reduce the need for dialysis and also reduce the mortality rate of CKD offers a significant opportunity for improved outcomes with substantial societal benefit.