Read about approvals and clinical trials
Where has Ammonaps (sodium phenylbutyrate) been approved?
Ammonaps (sodium phenylbutyrate) was approved to treat urea cycle disorders involving deficiencies by: The Food and Drug Administration (FDA), USA, on May 13, 1995, under the brand name Buphenyl; the European Medicines Agency (EMA), Europe, on Dec 8, 1999; The Therapeutic Goods Administration (TGA), Australia, on May 19, 2017, under the brand name Pheburane.
Please note that this medicine may have also been approved in other regions than the ones we’ve listed. If you have a question about its approval in a specific country feel free to contact our support team.
Urea cycle disorders
The Food and Drugs Administration (FDA) and the European Medicines Agency (EMA) approvals of Ammonaps (sodium phenylbutyrate) were based on data of a clinical trial that involved 82 patients with urea cycle disorders who were treated with sodium phenylbutyrate. Patients had not received other treatments for their disease before.
The main efficacy outcome was patient survival. The study also measured the number of hyperammonaemic episodes (periods of very high blood ammonia levels), cognitive development (development of the ability to think, learn and remember), growth, and blood ammonia and glutamine levels.
Amyotrophic lateral sclerosis (ALS)
The effects of clenbuterol on muscle function have been studied in various clinical trials.
Note: sodium phenylbutyrate has not yet been approved for treatment of ALS. Neurologists sometimes prescribe Ammonaps for off-label treatment of people suffering from ALS.
A phase 2 trial (NCT00107770), that involved 40 ALS patients, studied the safety of sodium phenylbutyrate. Patients received sodium phenylbutyrate for 20 weeks.
The phase 2 CENTAUR trial (NCT03127514) studied the efficacy of sodium phenylbutyrate (PB) combined with taurursodiol (TUDCA). In the trial, 89 participants were randomly assigned to receive 3g PB and 1g TUDCA twice daily for 24 weeks, while 48 participants received a placebo. Most participants (77%) of the trial were receiving an approved ALS therapy (riluzole, edaravone, or both) during and/or before starting the trial.
90 patients of the CENTAUR study participated its open‐label extension study to receive PB/TUDCA for up to 30 months
The main outcome measure of the phase 2 trial was tolerability. The study showed that sodium phenylbutyrate was well tolerated.
The main efficacy outcome of the CENTAUR study was ALS Functional Rating Scale (ALSFRS-R) score (which ranges from 0 to 48, with higher scores indicating better function). Results showed that PB/TUDCA treatment has both functional and survival benefits in ALS compared to placebo.
Patients who received the placebo declined by ±1.66 points per month. Patients receiving PB/TUDCA, declined by 1.24 points (a difference of 0.42 points or a 25% slowing of the progression rate). After 24 weeks of treatment, the absolute mean difference ALSFRS-R between treatment groups was 2.3 points. Analyses showed that the treatment effect was independent of whether a patient was also treated with approved ALS therapies during and/or before starting the trial
Clenbuterol improved the Myometer score significantly, both for the upper limbs (20% at 3 months and 23% at 6 months) as well as for the lower limbs (22% at 3 months and 27% at 6 months). The MRC score showed a trend toward improvement, but this was not statistically significant. The FVC score trended toward improvement at 3 months (5%) and was significant at 6 months (10%).
Results of the open-label extension showed that participants receiving PB/TUDCA lived significantly longer than those on placebo (25 months vs. 18.5 months or a 44% lower risk of death). After 2 years, ±51.6% of the patients receiving PB/TUDCA were still alive, compared to 33.9% of those in the placebo group.
Please refer to the summary of product characteristics below and in the resource section for comprehensive information about the safety and effectiveness of Ammonaps (sodium phenylbutyrate) for the approved indication.
Ammonaps (sodium phenylbutyrate), EMA product overview, cited on Oct 16, 2020
Safety Study of Oral Sodium Phenylbutyrate in Subjects With ALS (Amyotrophic Lateral Sclerosis), Clinical trial NCT00107770, cited on Oct 20, 2020
AMX0035 in Patients With Amyotrophic Lateral Sclerosis (ALS) (CENTAUR), Clinical trial CENTAUR (NCT03127514), cited on Oct 20, 2020
Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis, Paganoni S., NEJM, Sept 3, 2020
Long‐Term Survival of Participants in the CENTAUR Trial of Sodium Phenylbutyrate‐Taurursodiol in ALS, Paganoni S., Muscle & Nerve, Oct 16, 2020
Phase 2 study of sodium phenylbutyrate in ALS, Cudkowicz M., Amyotroph Lateral Scler., Apr 2009