Ucyclyd Buphenyl reimbursement to be managed by Corning HTA; orphan drug approved April 30.

UCYCLYD BUPHENYL REIMBURSEMENT NEGOTIATION TO BE HANDLED BY CORNING HTA following FDA approval of the powder version of the orphan drug for urea cycle disorders April 30. Ucyclyd has contracted with Washington, D.C.-based Corning HTA to conduct a provider-insurance program to assist in transitioning urea cycle patients on Buphenyl (sodium phenylbutyrate) from the clinical trials in which they are currently receiving the drug free of charge to a reimbursement setting with insurance companies, Corning HTA said.

Corning HTA is sending letters to the patients participating in Buphenyl clinical trials informing them of Buphenyl's approval and of the impending financial transition. Patients participating in Buphenyl studies account for an estimated 90% of the 200 patients afflicted with the disorder in the U.S., Ucyclyd said. Corning HTA also will send insurance companies information on Buphenyl, explaining the life-threatening nature of urea cycle disorders, the drug code and price and FDA approval.

The National Organization for Rare Disorders will administer a "compassionate use" patient assistance screening program in conjunction with Ucyclyd. NORD will conduct a financial review of patients who apply for free medication and evaluate whether the patient is in need of financial assistance. Those who qualify will receive the drug at no cost or at a reduced cost.

Buphenyl was designated "1P" by FDA, denoting a new chemical entity receiving a priority review. The powder version of sodium phenylbutyrate is indicated as adjuvant therapy in the chronic management of urea cycle disorders involving deficiencies of carbamylphosphate synthetase, ornithine transcarbamylase or argininosuccinic acid synthetase. Ucyclyd is expecting imminent approval of the tablet version of the drug.

Buphenyl is indicated in all neonatal-onset patients presenting in the first 28 days of life, and in patients with late-onset disease (presenting after the first month of life) who have a history of hyperammonemic encephalopathy. Urea cycle disorders are genetic disorders affecting a patient's ability to remove nitrogen from the body. All of the disorders have a specific liver enzyme deficiency that leads to increased amounts of ammonia in the blood, which may cause disturbed brain function and severe brain damage. The disorders vary in severity and in the age of those affected.

Untreated neonatal-onset urea cycle disease is "almost universally fatal" within the first year of life, labeling states. With hemodialysis, use of alternative waste nitrogen excretion pathways such as Buphenyl, dietary protein restriction and, in some cases, essential amino acid supplementation, the survival rate in newborns diagnosed after birth but within the first month of life is "almost 80%," Ucyclyd said. Most deaths occur during an episode of acute hyperammonemic encephalopathy.

Most patients taking the drug continue to experience recurrent episodes of acute hyperammonemia, labeling states.

Of 206 patients studied, the most commonly occurring adverse event was amenorrhea/ menstrual dysfunction in 23% of menstruating patients. Body odor and taste aversion were reported in 3% of patients. Decreased appetite occurred in 4% of the patients. A usual daily dose of Buphenyl powder is 450 to 600 mg/kg/day in patients weighing less than 20 kg, or 9.9 to 13 g/m2/day in larger patients. The administration of Buphenyl may be required indefinitely for patients, unless orthotopic liver transplantation is elected.

Phase IV commitments for the drug include conducting a formal pharmacokinetic study in pediatric and adult patients with urea cycle disorders, validating the batch manufacturing procedure, developing a test method to identify impurities in the drug substance and product and determining which foods and beverages are not compatible with Buphenyl powder due to their acidity.

Ucyclyd Pharma was incorporated in January 1995 and submitted NDAs for tablet and powder version of Buphenyl to FDA Feb. 15, 1995 ("The Pink Sheet" March 20, 1995, T&G-10). The firm has three employees, including Buphenyl discoverer Saul Brusilow, MD, of Johns Hopkins University. Pharmaceutics International will manufacture the drug for Ucyclyd.