dm+d

Unassigned

New Medicines

Xyndari (EU), Endari (US)Sickle cell disease

Information

Xyndari (EU), Endari (US)
New formulation
Emmaus Medical
Emmaus Medical

Development and Regulatory status

Filing withdrawn
Filing withdrawn
Launched
Yes
Yes

Oct 19: Emmaus Medical has withdrawn the marketing application before completion of the re-examination: it stated that this was based on a change in the company´s marketing strategy [18].


Jun 19: Emmaus Medical has appealed the CHMP decision and asked for a re-examination [17].


May 19: CHMP recommends refusal of a marketing authorisation. The committee did not consider that effectiveness has been shown due to the large number of early drop-outs in the clinical trial data presented: in the main study, more patients on active than placebo dropped out, and in the supplementary study, as well as many drop-outs, more patients on glutamine were taking hydroxyurea than those on placebo. The company may appeal the decision and ask for a re-examination within 15 days, however it is not allowed to present new data at this stage [16].


Mar 18: Emmaus Life Sciences and myTomorrows have made glutamine available through an Early Access Program (EAP) for treatment of patients with sickle cell disease that have exhausted other remaining treatment options [14].


Mar 18: Has been filed in EU using centralised procedure [13,14].


Dec 17: launched in US [11]; annual cost in US at published list price $40,515 for a 70Kg patient [12; Med Lett Drug Therap 2018; 60 (1539): 21].


Dec 17: Endari receives positive opinion for paediatric investigation plan from EMA. This allows the company to proceed with submission of a MA application for reduction of acute complications of sickle cell disease in adult and paediatric patients 5 years of age and older [10].


Jul 17: Emmaeus is planning a launch in Q4 2017, and says it will price Endari at a "reasonable" level to ensure patient access. Some of reported that the company is looking at charging somewhere between $11,000 and $18,000 a year for the product [9].


Jul 17. Approved in US [8].


Sep 16: Filed in US. A regulatory submission is also planned for EU [7].


Mar 15: No further update. Results from PIII study reported at ASH Dec 2014 [6].


Mar 14: Plan to file in US mid-2014 [5]


Has fast track status in the US [3].


Sep 12: Emmaus announced that its US PIII trial is nearing target enrollment completion. More than 190 of up to 225 patients are enrolled and final data collection is expected to be complete in 2013 [3].


Jul 12: Granted orphan drug status in EU for the treatment of sickle cell disease (EU/3/12/1011). It received orphan drug status in the US in 2007 [2].

Sep 16: Phase 3 trial (n=230 in US) reported reduction in frequency of sickle cell crises and hospitalisations, as well as a reduction in cumulative days hospitalised, and a lower incidence of life-threatening acute chest syndrome [7].


Mar 14: Preliminary analysis of data from the PIII study indicate both the primary and secondary endpoints were met. The prospective, randomized, double-blind, placebo-controlled, multi-centre trial enrolled 230 adults and children from 5 years of age. There was a statistically significant 25% reduction in the median frequency of sickle cell crises (p=0.008) over a 48-week period (primary endpoint). There was also a statistically significant 33% reduction in median frequency of hospitalizations (p=0.018). The therapy demonstrated a well-tolerated safety profile [5]


Dec 12: Enrollment in PIII study competed [6].


NCT01179217 is a multicentre PIII double-blind RCT of L-glutamine therapy vs placebo in 225 patients with sickle cell anaemia or sickle ß0-thalassemia. The primary outcome is the number of sickle cell crises over 48 weeks. The study started in May 10 and is due to complete Aug 13 [1].

Category

Amino acid - oral powder formulation of L-glutamate, a precursor of an enzyme called NAD, which is thought to be important for the functioning of the oxygen-carrying hemoglobin molecule.
Sickle cell disease affects not more than 2.1 in 10,000 people in the EU; equivalent to a total of not more than 106,000 people [2].
Sickle cell disease
Oral

Further information

Yes
To be confirmed

Trial or other data

Jul 18: Results of NCT01179217 published in NEJM [15].


Sep 16: Phase 3 trial (n=230 in US) reported reduction in frequency of sickle cell crises and hospitalisations, as well as a reduction in cumulative days hospitalised, and a lower incidence of life-threatening acute chest syndrome [7].


Mar 14: Preliminary analysis of data from the PIII study indicate both the primary and secondary endpoints were met. The prospective, randomized, double-blind, placebo-controlled, multi-centre trial enrolled 230 adults and children from 5 years of age. There was a statistically significant 25% reduction in the median frequency of sickle cell crises (p=0.008) over a 48-week period (primary endpoint). There was also a statistically significant 33% reduction in median frequency of hospitalizations (p=0.018). The therapy demonstrated a well-tolerated safety profile [5]


Dec 12: Enrollment in PIII study competed [6].


NCT01179217 is a multicentre PIII double-blind RCT of L-glutamine therapy vs placebo in 225 patients with sickle cell anaemia or sickle ß0-thalassemia. The primary outcome is the number of sickle cell crises over 48 weeks. The study started in May 10 and is due to complete Aug 13 [1].

Evidence based evaluations