The U.S. Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee voted 10-3 to support the approval of L-glutamine powder for the treatment of sickle cell disease (SCD).
The committee’s decision was based on a review of the efficacy and safety of L-glutamine in a phase III, randomized, multicenter, double-blind, placebo-controlled study in patients with SCD who were 5 years or older at time of treatment. Patients had at least two episodes of painful sickle cell crises (defined as a visit to the emergency room or facility for pain treatment) in the year before enrollment.
The trial randomized 298 participants 2:1 to receive either oral L-glutamine 0.3mg/kg/day (n=151) or placebo (n=78) for 48 weeks, followed by a 3-week tapering period. Randomization was based on baseline hydroxyurea use.
The frequency of sickle cell crises (the study’s primary endpoint) was lower in the L-glutamine arm, compared with the placebo-treated patients (median = 3 vs. 4; p=0.0052). The rates of early discontin t0 ).4uation were 36 percent in the L-glutamine arm and 24 percent in the placebo arm, but, despite the differential dropout, analyses showed that L-glutamine had a range of reduction in the rate of crises per 48 weeks from 0.4 to 0..
The safety analysis included 187 patients treated with L-glutamine and 111 patients treated with placebo. Most patients experienced a serious adverse event, the most common of which were:
- sickle cell anemia with crisis (66.3% L-glutamine arm; 72.1% placebo arm)
- acute chest syndrome (7% L-glutamine arm; 18.9% placebo arm)
The most common adverse reactions (occurring in ≥10% of patients and at greater rates than with placebo) were: constipation, nausea, headache, cough, pain in extremity, back pain, chest pain, and abdominal pain.
Source: FDA ODAC memo, May 24, 2017.