Improved Outcomes with UX007 in LC-FAOD Patients Treated Via an Expanded Access Program

Authors: Jinay Shah, RPh, MS1; Brian King1; Hank Mansbach, MD1; Sarah Chesler, BSN1; Emil Kakkis, MD, PhD1; Deborah Marsden, MD1

1Ultragenyx Pharmaceutical Inc., Novato, CA, USA

Corresponding Author:  Jinay Shah, RPh, MS, Ultragenyx Pharmaceutical Inc., Novato, CA, USA

Corresponding Author contact information:; 415-483-8228

In spite of optimized dietary regimens including even-carbon medium chain triglycerides (MCT), patients with long-chain fatty acid oxidation disorders (LC-FAOD) may still experience major clinical events (MCEs; ie, rhabdomyolysis, cardiomyopathy, hypoglycemia) leading to hospitalizations and potentially death. UX007, an odd-carbon medium chain triglyceride, is being investigated for the treatment of LC-FAOD. An active global Expanded Access Program    (EAP) with UX007 for LC-FAOD has been ongoing since February 2013.  The EAP includes three mechanisms for qualified patients: 1) emergency access to investigational new drugs (eIND), 2) individual compassionate use, and 3) (in France only) nominative Temporary Authorisation for Use (nATU).

To evaluate the ongoing EAP, information was requested via questionnaire from physicians treating patients with LC-FAOD under the EAP, focused on patient demographics, disease history, prior therapy, diet management, and treatment outcome while on UX007.

As of January 01, 2018, 56 critically ill patients with severe LC-FAOD (19 eIND, 25 compassionate use, and 12 nATU) have been treated with UX007 under the EAP; completed questionnaires were received for 39 patients (14 eIND, 16 compassionate use, and 9 nATU). The majority of the patients had LCHAD (33%) and VLCAD (31%). Most of the patients had a history of MCEs prior to treatment with UX007: rhabdomyolysis (74%), hypoglycemia (61%), and cardiomyopathy (51%). Almost all (95%) of patients were treated by a metabolic physician, had their diet managed following dietary guidelines by a dietician trained in metabolic disorders, and were reported to be compliant with their management prior to initiating UX007 treatment.

According to the physician responses to the questionnaire, 85% of patients experienced improvement in MCE and 79% of patients demonstrated an overall improvement in long-term LC-FAOD outcome during UX007 treatment. Three patients (8%) had worsening of MCEs. Two of these patients started treatment when they were critically ill and subsequently died due to the underlying disease (treated with UX007 for 3 and 5 days, respectively). The median duration of treatment with UX007 for all patients was 8.6 months (range: 0.1 to 53.7 months).

As of January 1, 2018, 74% of patients receiving UX007 in the EAP continue treatment with UX007; 26% of patients discontinued treatment. The reasons for discontinuation of UX007 treatment were death (15%), GI intolerance (3%), cardiac arrest (3%), recurring emesis (3%), and not provided (3%). None of the deaths were attributed to UX007. The treating physician(s) attributed all of the deaths that led to discontinuation of UX007 to the underlying disease.

Overall, treatment with UX007 led to improved short- and long-term outcomes in the majority of patients receiving UX007 in the EAP, and majority of patients continue UX007 treatment. The observed benefit and additional comments provided by the physicians support the stabilization and treatment effect of UX007 in critically ill patients with LC-FAOD. The data from the EAP show that patients with severe LC-FAOD continue to have significant unmet need despite current dietary management. These findings underscore the need for urgent early intervention, and treatment with UX007 may improve the outcome of major medical events.

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