SBIR-STTR Award

The long-term goal is to determine the feasibility of assembling successful New Drug Applications for two Investigation New Drugs currently undergoing Phase III FDA approved studies. The drugs under study include the oral dosage form of sodium phenylbutyrate and the intravenous dosage form of sodium benzoate and phenylacetate. Because their indicated use is for a group of rare urea cycle disorders (deficiencies of carbamyl phosphate syntbetase, ornithine transcarbamylase, and argininosuccinic acid synthetase) which have an estimated combined incidence of 1 in 25,000, there has not been interest from the pharmaceutical industry. The specific aims of this Phase I are to determine if the clinical and laboratory database currently available in FDA approved Phase III studies are sufficient to meet the FDA's New Drug Application requirements as well as to determine if contract manufacturing arrangements that meet FDA's Good Manufacturing Practice requirements can be made. If this Phase I demonstrates such feasibility, we will, in Phase II, submit New Drug Applications to the FDA with the expectation of marketing these drugs for these rare diseases.Awardee's statement of the potential commercial applications of the research:Orphan drugs for the treatment of urea cycle disorders have been developed and shown to be safe and effective in federally funded research. If this Phase I study determines that sufficient clinical and laboratory data exist, NDAs for intravenous and oral dosage forms of the drugs will be prepared and filed to commercialize these drugs.National Institute of Child Health and Human Development (NICHD)

This proposal will commercialize treatment for three rare inborn errors of urea synthesis; deficiencies of carbamyl phosphate synthetase, ornithine transcarbamylase and argininosuccinic acid synthetase. These diseases in the their most severe form are fatal in the first months of~life an cause mental retardation m the milder cases, all of which are a consequence of a failure to synthesize urea nitrogen and the resulting accumulation of ammonia. The treatment consists of an oral dosage form of sodium phenylbutyrate (IND # 17123) a pro-drug which is beta oxidized to phenylacetate which in turn conjugates with glutamine to yield phenylacetylglutamine which serves a substitute for urea nitrogen as a vehicle for waste nitrogen excretion. An intravenous dosage form is also available using a combination of sodium benzoate and sodium phenylacetate. These drugs have proven to prolong survival in the most serious form of these diseases and prevent deterioration of intelligence in the milder forms of the disease. This project is designed to collate and interpret data collected during a FDA phase 3 Investigational New Drug study to assemble and submit New Drug Application will enable the products to be manufactured, marketed and distributed in accordance with Food and Drug Statutes. As a result, patients will have guaranteed and uninterrupted access to an approved drug.Awardee's statement of the potential commercial applieations of the research:If the Specific Aims are achieved new drugs will be available by prescription for patients with urea cycle disorders.National Institute of Child Health and Human Development (NICHD)