Regulatory Decision Summary for Plenvu

This New Drug Submission (NDS) was filed to obtain market authorization for Plenvu (polyethylene glycol (PEG) 3350, sodium ascorbate, sodium sulfate anhydrous, ascorbic acid, sodium chloride and potassium chloride powder for oral solution), an osmotically acting laxative, for cleansing of the colon in preparation for colonoscopy in adults. Upon review of the submitted data package, Health Canada authorized Plenvu as filed.

Health Canada considers that the benefit-harm-uncertainty (BHU) profile of Plenvu (polyethylene glycol (PEG) 3350, sodium ascorbate, sodium sulfate anhydrous, ascorbic acid, sodium chloride and potassium chloride powder for oral solution) is favourable for cleansing of the colon in preparation for colonoscopy in adults.

The safety and efficacy of Plenvu for the cleansing of the colon in preparation for colonoscopy in adults were assessed in a Phase III, non-inferiority, multicenter, randomized, parallel group, investigator-blinded clinical trial (NER1006-02/2014 [MORA]) in male and female participants aged 18 to 85 years (inclusive) who were undergoing a screening, surveillance, or diagnostic colonoscopy. In this study, the bowel cleansing efficacy of Plenvu using two different dosing regimens (2-Day Split-Dosing regimen and 1-Day Morning Split-Dosing regimen) was compared to an active comparator (MOVIPREP, a 2 Liter PEG Plus Electrolytes Oral Solution) using one dosing regimen (2-Day Split-Dosing regimen). A total of 849 participants were randomly assigned in a 1:1:1 ratio to receive Plenvu 2-Day Split-Dosing, Plenvu 1-Day Morning Split-Dosing, or MOVIPREP 2-Day Split-Dosing. The primary efficacy endpoint was the proportion of participants achieving “overall bowel cleansing success”, which was defined by a result of Grade A or B (Grades A or B corresponding to full visualization of the bowel mucosa on the Harefield Cleansing Scale [HCS]), as assessed on withdrawal of colonoscope. All treatment groups achieved successful bowel cleansing (Plenvu 2-Day Split-Dosing treatment group: 92.0%, Plenvu 1-Day Morning Split-Dosing treatment group: 89.1%, and MOVIPREP treatment group: 87.5%). Both the Plenvu 2-Day Split-Dosing regimen and the Plenvu 1-Day Morning Split-Dosing regimen were shown to be non-inferior to the comparator.

The safety data showed that the most common adverse reactions (> 2%) in the Plenvu treatment groups were vomiting, nausea, signs and symptoms of dehydration, and abdominal pain/discomfort. Overall, the safety review for Plenvu did not raise any apparent specific safety concerns beyond what is known for this drug class. The safety concerns regarding Plenvu as well as the drug class have been addressed through appropriate labelling in the Plenvu Product Monograph.

The chemistry and manufacturing information submitted for Plenvu has demonstrated that the drug substances and drug product can be consistently manufactured to meet the approved specifications.

The final labelling and Product Monograph are considered acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for Plenvu for the approved indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Plenvu please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.