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news.10 adult subjects with urea cycle disorders dosed
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Hyperion Therapeutics has reported positive top-line results from its Phase II study of HPN-100 for the treatment of urea cycle disorders.
The Phase II study was an open-label, fixed sequence, switch-over study [Buphenyl (sodium phenylbutyrate) to HPN-100] of 10 adult subjects with urea cycle disorders (UCDs). The primary endpoint was safety; secondary outcome measures included pharmacokinetics (PK), pharmacodynamics, and exploratory efficacy as measured by time-normalized area under the curve (TNAUC) for ammonia.
Patients were enrolled on their stable dose of Buphenyl and 24-hour PK, ammonia measurements, amino acids, and urine collections were completed in a study unit after seven days of on-study treatment. Each patient was then switched to HPN-100 at a dose providing the same amount of the active ingredient (PBA). After seven days of HPN-100 dosing, patients were re-admitted for the same battery of assessments that were completed at day seven. Both Buphenyl and HPN-100 were administered TID with meals.
A total of 21 adverse events (AEs) occurred in seven subjects during Buphenyl treatment and 15 AEs occurred in five subjects with HPN-100. There were two serious adverse events (SAEs) related to hyperammonemia; both occurred during 100% Buphenyl treatment. No SAEs occurred during 100% HPN-100 treatment. Ammonia values were approximately 30% lower on HPN-100 assessed as TNAUC over 24 hours [mean (SD) = 38.4 (19.6) versus 26.1 (10.3) umol/l), Cmax = 79.1 (40.1) versus 56.3 (27.9) umol/l, or the percentage of normal values: 58% versus 72%]. Differences in ammonia values were not statistically significant.
Hyperion and Ucyclyd Pharma, a subsidiary of Medicis Pharmaceutical, entered into a collaboration agreement for HPN-100 in August 2007. Under the terms of the agreement, Hyperion is conducting ongoing R&D of HPN-100 for urea cycle disorders, hepatic encephalopathy, and other forms of hyperammonemia.
Don Santel, CEO of Hyperion Therapeutics, said: We are very pleased with the study results and our recent end of Phase II meeting with the FDA. We are currently finalizing our Phase III study protocol in consultation with the agency and are eager to further explore the potential of HPN-100 for the treatment of UCDs.