Regulatory Decision Summary for Benvyon

As the active medicinal component and the proposed indications for Benvyon are identical to those of Treanda, the Reference Product for bendamustine, the Sponsor provided summaries of clinical efficacy, safety, pharmacology, and non-clinical data based predominantly on information from published literature, foreign public assessment reports, and the Treanda Product Monograph (PM).

The efficacy data for Benvyon for the proposed indications are based on 2 pivotal trials conducted with Treanda: a multicentre, open-label, single-arm trial of bendamustine in 100 patients with indolent NHL who were non-responsive to or progressed on a rituximab regimen, and a randomized, open-label trial of bendamustine vs chlorambucil in 319 previously untreated patients with Binet stage B or C CLL. The pivotal studies provide evidence for the efficacy of bendamustine for the proposed indications of indolent NHL refractory to rituximab, and the front-line treatment of CLL.

The safety profile of Benvyon is based on the pivotal trials and post-marketing experience described in the Treanda PM. All significant safety risks identified for Treanda are also considered to apply to Benvyon and are reflected in the Warnings and Precautions section of the Benvyon PM.

Key clinical pharmacology and non-clinical findings are similar to other bendamustine products in Canada. The excipients used in Benvyon (ethanol, polyethylene glycol 400, and butylated hydroxyanisole) are not expected to affect the clinical action or pharmacokinetics of bendamustine.

Additionally, as Benvyon is a ready-to-use solution that is more concentrated (25 mg/mL) than the lyophilized bendamustine products currently available in Canada (5 mg/mL after reconstitution), there is potential for medication error due to confusion between the available formulations. A Risk Management Plan (RMP) for Benvyon was submitted by the Sponsor to Health Canada. The RMP is designed to describe known and potential safety issues, to present the monitoring scheme and when needed, to describe measures that will be put in place to minimize risks associated with the product. Upon review, the RMP was considered to be acceptable. The Market Authorization Holder (MAH) will be requested to submit reports of the Canadian cases of “Medication Errors” to the MHPD on a quarterly basis for review by the Patient Safety Section (PSS) for 2 years following approval. There will be no need for submitting PSURs/PBRERs, since the safety profile of bendamustine has been sufficiently characterized through the long-term post market experience with Treanda.

A Notice of Compliance (NOC) pursuant to section C.08.004 of the Food and Drug Regulations was recommended from a Quality perspective.

The labelling documents conform to the necessary regulatory requirements and are consistent with the labelling guidance documents.

In summary, Benvyon contains the same active medicinal ingredient, carries the same indications, and is intended to be infused at the same concentrations as other bendamustine products available in Canada, but is supplied as a concentrated solution instead of a lyophilized powder. Safety concerns regarding medication errors are considered manageable at this time. Therefore, Benvyon is considered to have a positive benefit-risk profile under the proposed conditions of use.

For more details on Benvyon, please consult the product monograph, approved by Health Canada and available in the Drug Product Database.