The Pink Sheet reports on a very urgent ethical question:
FDA's Endocrinologic and Metabolic Drugs Advisory Committee on Jan. 13 will consider whether Orphan Europe can use positive results from patient experience with carglumic acid to demonstrate efficacy of the firm's Carbaglu for treating hyperammonemia associated with NAGS deficiency, given the difficulty of conducting a clinical study in the orphan setting.
A controlled clinical trial in this target patient population "cannot be conducted because the disease has an extremely low incidence, it is life-threatening, severely symptomatic, and hyperammonemic decompensation leads to quick deleterious neurological/psychomotor consequences," Orphan Europe maintains in briefing material for the committee meeting.
A deficiency of N-acetyl-glutamate synthase is one of the rarest of the urea cycle disorders, which have an overall occurrence rate of approximately one per 30,000 live births. It results in hyperammonemia - high blood ammonia levels - that can lead to death or neurological impairment.
Instead of conducting a trial, the sponsor submitted a retrospective review of the effect of carglumic acid on both short-term and long-term plasma ammonia levels in 23 patients diagnosed with NAGS deficiency. Carbaglu is the pharmaceutical grade of carglumic acid, which has been used as a chemical grade product by clinicians. Also submitted in support of the NDA were interim data for three patients in an open-label, Phase II clinical trial of three days duration.
