Regulatory Decision Summary for Netvision

This New Drug Submission (NDS) relied on publicly available data in the scientific literature in accordance with the Health Canada guidance document Drug Submissions Relying on Third-Party Data (Literature and Market Experience) to support market authorization of Netvision. Fifteen (15) pivotal studies were identified by the Sponsor through a systematic literature review to support the use of ⁶⁸Ga-DOTATATE PET/CT for the detection and localization of SSTR-positive NETs. These studies represented 875 patients with well differentiated (Grade I or Grade II) neuroendocrine tumours (NETs) who underwent ⁶⁸Ga-DOTATATE PET/CT imaging between the years 2010 and 2019. The different NET subtypes included were gastroenteropancreatic (GEP)-NET, pheochromocytoma and paraganglioma (PPGL), mixed/unknown NET and medullary thyroid carcinoma (MTC).

The ⁶⁸Ga-DOTATATE PET/CT protocol, including the dosing regimen and timing of imaging post-administration, was similar across studies. Intravenous administration of ⁶⁸Ga-DOTATATE was at a dose of 100 - 200 MBq and the mean start of imaging was reported as 40 to 65 min post-injection (p.i). Primary efficacy endpoints were ⁶⁸Ga-DOTATATE PET/CT sensitivity and specificity for the detection and localization of SSTR-positive NETs. The results demonstrated that ⁶⁸Ga-DOTATATE is a highly sensitive and specific diagnostic radiotracer which often identified more lesions and, in many cases, additional lesions that had been missed by other imaging techniques. Due to inherent limitations with these studies (e.g. small cohort sizes and mixed patient populations), no statistical inferences can be made and therefore only descriptive data is in the Product Monograph.

Intravenous administration of microdose chemical levels (≤ 50 µg) of ⁶⁸Ga-DOTATATE is not intended to elicit any pharmacological effects. Data from the literature identified no serious or severe adverse drug reactions to ⁶⁸Ga-DOTATATE in the individual studies. The adverse reactions (ADRs) reported were infrequent, non-serious and transient. No serious adverse reactions were identified in these studies. ADRs included nausea/vomiting, injection site conditions and hypersensitivity reactions as well as tachychardia, abdominal pain and unilateral whole-body edema. Based on identified and potential risks, appropriate warnings and precautions are included in the Product Monograph. 

NET diagnosis can be difficult because of tumour heterogeneity, variable primary locations, indolent tumour biology and typically small lesions. Since diagnosis is often not confirmed until patients have progressed to late stages of disease, limited therapeutic options are available and highly specific and sensitive diagnostic imaging modalities are needed. The high degree of sensitivity and specificity of ⁶⁸Ga-DOTATATE PET/CT for localization and detection of SSTR-positive NETs along with its favourable safety profile support its use for the proposed indication. A Notice of Compliance was granted.