Regulatory Decision Summary for Essepna

Overall, the benefit- harm-uncertainty profile is favorable for the approval of Essepna as a stand-alone amino acids parenteral solution, in the indication sought by the sponsor.

Essepna (Amino acids injection 10% w/v) is a combination of various amino acids. It is indicated for supply of amino acids as part of a parenteral nutrition regimen for patient unable to ingest oral or enteral nutrition to provide the required nutrients, and prevent malnutrition and its complications.

Essepna was introduced to Health Canada as one of the components of SmofKabiven Electrolyte Free (EF), a 3-chamber bag containing an amino acids solution, a lipid emulsion, and dextrose, which was approved in April 2015. During the review of SmofKabiven EF NDS submission, each of the three components were found acceptable individually for the approval of SmofKabiven EF, including the safety and efficacy of Essepna as the amino acids component. In the current submission for Essepna as a stand-alone drug, the main supportive safety and efficacy information was based on one pivotal clinical study (AS-CS-01-FR) included in the SmofKabiven EF submission. Therefore, no new clinical trials were provided with the current submission, which is acceptable.

In the pivotal study mentioned above, the efficacy and safety of Essepna (under the European brand name Cosmosteril 10 %) was compared to that of Nutrilamine 16 (a formulation of amino acids approved in Canada), in intensive care patients requiring total parenteral nutrition for 6 days. The two products were considered equivalent as the difference in the cumulated nitrogen balance at day 6 (the primary efficacy endpoint) did not exceed 5 g (p = 0.48). The safety of Essepna was assessed for the approval of SmofKabiven EF mainly based on the same study, which showed that adverse events with Essepna were unremarkable, with no deaths or treatment-related adverse reactions. One adverse event (alkaline phosphatase elevations) related to the drug was reported in each treatment group. One serious adverse event (septic shock) was reported in the Essepna group but was determined to be not related to the drug.

Post-marketing data collected over a 5-year period (between 2014 and 2019) showed that a number of adverse drug reactions (ADRs) were reported, including serious ADRs. However, the causal relationship between the ADRs and the drug could not be established due to confounding underlying conditions and/or co-suspect drugs. It is noteworthy, that Essepna in parenteral nutrition provides amino acids that would normally be present in the human body through daily natural feeding. Therefore, amino acids administered through parenteral nutrition, when oral or enteral feeding is insufficient or impossible, are not expected to have significant adverse effects if they are provided in adequate quantities and within physiologically acceptable limits. Overall, based on the evidence submitted by the sponsor, the safety profile of Essepna is acceptable.

Since the non-clinical data for Essepna was found acceptable as per the approval of SmofKabiven EF, in the current submission, the Sponsor submitted only two new non-clinical toxicology studies assessing the local tolerance in rabbits, and the hemolytic and biocompatibility properties of Essepna. The results did not reveal any significant issues.

In conclusion, the safety and efficacy information provided in this submission has demonstrated that Essepna is safe and effective as an amino acids solution for parenteral nutrition. A Notice of Compliance is recommended.